• Some bacteria complete the cell cycle in 9 minutes.

• Viruses pass through filters that remove bacteria (≤0.45um)

–Bacteria 0.4-2um and human eye sees ≥30um.
• Shape determined by cell wall: Bacilli (rod), Vibrio (comma), Spirochetes (coil), Cocci
(sphere) = pair(diplo), chain(strepto), tetrad(micro), cluster(staphylo)
• Amount of peptidoglycan determines Gram Stain.
–Positive = thick, teichoic acid – peptidoglycan is permeability barrier.
–Negative = thin, lipopolysaccharides – outer membrane is permeability barrier.
• Teichoic acid – (GlcNAc and MurNAc) – water-soluble polymers of polyol phosphates –
covalently linked to peptidoglycan – important factor of virulence.
• Lipoteichoic acid – anchored to cytoplasmic membrane.
• Shwartzman reaction is disseminated intravascular coagulation following release of large
amounts of endotoxin (LPS).
• Outer membrane of Gram(-) bacteria allows passage of small hydrophilic metabolites or
antibiotics (<700Da through porins), but stops large hydrophobic antibiotics and lysozymes.
–Has adhesion sites to cell membrane and linked by lipoprotein to peptidoglycan.
–Held together by Mg2+ and Ca2+ linkages b/w phosphates/LPS/proteins.
–LPS → membrane-(Lipid A-core polysaccharide-O antigen) – Lipid A is toxic (fever).
• Innate immune response is mediated by neutrophils and macrophages that recognize PAMPs
(Pathogen Associated Recognition Pattern) with Toll-like receptors for release of cytokines.
–PAMPs essential for pathogen survival – well conserved – specific for given TLR.
–LPS (Gram-), Lipoteichoic Acid (Gram+), Mannon (yeast), Lipoprotein (eubacteria),
Lipoarabinomonnan (mycobacterium)
Peptidoglycan
-NAM-NAG-NAM-NAG-NAM-NAG-
L-Ala
D-Glu
Lys or DAP -*-D-Ala * = 5x Gly in Gram(+)
D-Ala L-Lys or DAP Lys = Gram(+) and DAP = Gram(-)
D-Glu
L-Ala
-NAM-NAG-NAM-NAG-NAM-NAG-
• Some virulence factors come from duplication of basal body genes of the flagellum to
perform functions independent of motility.
–Type II – secretion out of bacterium
–Type III/IV – delivery into eukaryotic cells
–Type III delivers cytotoxin directly into cell to neutralize innate immunity.
• The capsule is poorly antigenic and antiphagocytic and is a major virulence factor.
• The tetrapeptide in peptidoglycan contains both D and L amino acids.
• A diamino amino acid (lysine, diaminopimelic, diaminobutyric) is needed at 3rd position for
crosslinking – a fifth amino acid (D-Ala) is released to form an amino acid trade.
• Transpeptidases and DD-carboxypeptidases catalyze cross-linking reaction and are also
penicillin-binding proteins. – Penicillin and b-lactam antibiotics resemble the “transition
state” conformation of the D-ALA-D-ALA unit.
• Some Gram(+) bacteria can form spores, but never Gram(-) bacteria.
• Minimum growth requirement = carbon and nitrogen, energy source, water, and various ions.
• Ribosomes make a good target for antibiotics, but the cell wall is the optimal target.
• Bacteria have a simple cytoskeleton, but complex cytoplasmic membrane.
• Pathogenic E. coli possess additional DNA (25%) that contribute to pathogenesis.
• DNA composition is more accurate than morphology and is advantageous because it can
have automation, productivity, speed, and accuracy.
–PCR, ligase chain reaction, RFLP (individual source if same among patients).
Whipple’s disease – Tropheryma whipplei – fever, weight loss, diarrhea, polyarthritis, skin
hyperpigmentation – biopsies have periodic acid-Schiff-positive staining macrophages.
–Currently diagnosed by cytological tests, but going to PCR (16S rRNA) in the future.
–Initially treat with penicillin or 3rd generation cephalosporin, or trimethoprim-
sulfamethoxazole and on the long-term with TMP-SMZ or doxycycline.
• Pseudomonads and Streptococci use pentose phosphate pathway in the absence of glycolysis.
• Fermentation has pyruvate as electron acceptor, while respiration uses O2 or NO3.
Aerobe = only in presence of O2 – (Cytochrome C is terminal oxidase)
Microaerophile = only in presence of low O2
Facultative anaerobe = use O2 if present or ferment if not – (Cytochrome D is terminal oxidase)
Anaerobe = only in absence of O2
Aerotolerant = ferment in presence or absence of O2
Psychrophilic = -5° to 30°C (10° - 20°C)
Mesophilic = 10° to 45°C (20° - 40°C)
Thermophilic = 25° to 80°C (50° - 60°C)
Halophilic = require up to 30% (5M) NaCl for growth – MS media selects for Gram(+) bacteria
Enterobacteriaceae Diagnostic – Formate → CO2 + H2 (acidic conditions)
(+) E. coli & Salmonella (-) Shigella & S. thyphi
Butanediol Fermentation – Pyruvate → acetolactate → Acetoin* → Butanediol
*Voges-Prozkauer reagent (-) = E. coli (sewage) and (+) = Enterobacter spp. (vegetation)
–Tests for Enterobacter, Bacillus, Serracia
• Lag (no division) – Exponential – Stationary (↓ nutrients/pH, ↑ toxic products) – Death
• Spore formation: Bacillus, Clostridium, Sporosarcina
• Resist antibiotics by: efflux pumps, modifying targets, destroying antibiotic.
• Antiseptics are for skin application while disinfectants are for inanimate objects
–Alcohol – denature protein –Heavy metals – bind SH to denature proteins
–Alkylating agent – epoxide bridges –Phenols – disrupt membrane by intercalating
–Halides – oxidizing agent –QACs – disrupt membrane by intercalating
–UV radiation – damages DNA QAC = Quaternary ammonium compound
• Triclosan is a di-phenolic compound that specifically inhibits an enzyme involved in fatty
acid biosynthesis. – was originally added to plastics, but then in soap – resistance developed.
• Penicillin was discovered by Fleming.
Fungi: Penicillium, Cephalosporium Bacteria: Streptomyces, Bacillus, Microspora.
• Bacteriostatic only inhibits growth – Tetracycline, Sulfonamide, Chloramphenicol.
• Bactericidal directly kills (needed if immuno-compromised) – Streptomycin, Penicillin.
Adverse effects include: 1)toxic side effects, 2)hypersensitivity, 3)masking w/o eliminating,
4)alteration of normal flora (allows ↑ Clostridium difficile → diarrhea from endotoxins A/B).
–Tetracycline (tooth discoloration), Chloramphenicol (anemia), Streptomycin (auditory damage)
Mechanisms of Antibiotics
• Block transpeptidation (peptidoglycan synthesis), bind penicillin binding proteins, autolysins.
–β-lactams (penicillins, cephalosporins, carbapenems, monobactams).
• Binds to D-Ala-D-Ala to block transglycosylation/transpeptidation (peptidoglycan synthesis).
–Glycopeptides.
• Binds 30S subunit of bacterial ribosome.
–Aminoglycosides, Tetracyclines.
• Binds 50S subunit of bacterial ribosome.
–Macrolides/lincosamides, Streptogramins, Oxazolidinones.
• Binds DNA gyrase.
–Fluoroquinolones.
• Binds β-subunit of bacterial RNA polymerase.
–Rifampin.
• Inhibits enzymes in tetrahydrofolate production.
–Trimethoprim/sulfonamides.
• Interferes with DNA replication.
–Metronidazole.
Peptidoglycan Biosynthesis
1)Precursor synthesis in cytoplasm – blocked by Phosphonomycin.
2)Transport of disaccharide subunit in membrane by bactoprenol – blocked by Bacitracin.
3)Assembly and cross-linking outside – blocked by glycopeptides and β-lactams/glycopeptides.
β-lactam Resistance – (Penicillin/Cephalosporin)
1)Decrease permeability – mutation in porin – non-specific to ↑ resistance to several drugs.
–Seen only in Gram(-) bacteria.
2)Mutation in PBPs – specific to ↑ resistance to specific drug (ex- Streptococcus pneumoniae)
3)Inactivation – primary mechanism – β-lactamase – can be transferred on plasmids.
–Each specific enzymes targets specific subsets of b-lactams.
• There is a 5% cross-allergy for Penicillin and Cephalosporin.
• Antimicrobials do not inhibit transcription, but can inhibit translation because of the
difference between prokaryotic and eukaryotic ribosomes.
–Tetracylines – bacteriostatic – binds PO4 on 30S to interfere with aminoacyl t-RNA.
–Has 4 sites for modification to be better absorbed with longer half-life.
–Inhibits both prok./euk.–toxic only to prok. due to active transport/accumulation.
–Resistance from efflux pump or mutation to ribosome.
–Aminoglycosides (kanamycin, gentamicin) – bactericidal – inhibit formation of 30S
initiation complex to ↓ rate of protein synthesis.
–Limited permeability so used with β-lactams, which synergistically disrupt
peptidoglycan for more efficient entry.
–Resistance via covalent modification – addition of phosphoryl, adenyl, or acetyl.
–Erythromycin – bacteriostatic/bactericidal (↑ conc.) – binds 50S to block release of
deaminoacyl-tRNA.
–Resistance via erm gene to methylate rRNA – this is an attenuation (response to
antibiotic, not selection of a resistance gene) – this adaptation is reversible.
–Metronidazole – treats anaerobic bacterial infection via DNA damage from radicals.
–There are few drugs that inhibit DNA because synthesis is same in prok./euk.
 –Quinolines – inhibition of bacterial DNA gyrase.
–1st generation – Nalidixic acid – synthetic quinoline – narrow spectrum leads to
rapid selection of resistant mutants – not useful clinically.
–2nd generation – Cypro – fluorinated quinoline – 100x more active – ↑ spectrum
to include Enterococcus, Staphylococcus, Pseudomonas, Bacillus antraces.
–Resistance via point mutation on DNA gyrase.
• Metabolic analogues can also act as antimicrobial agents by competitive inhibition
–Sulfonamides – analog to p-Aminobenzoic acid (pABA) –inhibits dihydrofolate synthetase.
–Synthetase is unique to bacteria, while mammals need folic acid for growth.
–Trimethoprim – analog to dihydrofolate – inhibits dihydrofolate reductase.
–Bacterial reductase has high affinity for trimethoprim, while mammals have low affinity
• Combining drugs good for prompt treatment, mixed infections, delaying resistance, synergy.
Synergy
–Sulfonamides & trimethoprim block sequential steps in folic acid synthesis.
–Penicillins enhance uptake of aminoglycosides.
–Clavulanic acid inactivates β-lactamase to protect penicillin.
• Resistance to antibiotics may be innate if target is missing or by mutations (low frequency
for low level resistance) and genetic exchange (clinically significant).
–Selection for resistance to one antibiotic allows for acquired resistance to several.
• Strategies to fight resistance are to modify current drugs instead of making new ones and to
use drug rotation to reduce selection.
Bacterial Viruses and Lysogeny
• Virion is a package of nucleic acid whose production requires invasion of a host cell.
–Viroids have ONLY nucleic acid. –Prions have ONLY protein.
• Viral genome is either ss- or ds- RNA or DNA, circular or linear, one or multi chromosomes.
• There are no ribosomes for protein synthesis and cannot make ATP.
• Two capsid shapes are: 1)helical (filamentous) where specific viral protein winds around
nucleic acid (length directly related to length of genome), and 2)icosahedral (spherical)
where multiple viral proteins are needed.
–Some viruses have an envelope derived from nuclear or cytoplasmic membrane lipids
from infected cell – are inactivated by detergents and organic solvents.
Infection Timeline
0 mins – virus attaches via its surface proteins to host receptors (used by host for other purpose).
–A given virus “prefers” specific hosts based on proteins and receptors.
–Virion enzymes attack cell wall to create a small opening.
2 mins – host machinery transcribes viral genome to make “early” proteins.
–early proteins alter physiology of cell – are required for synthesis new viral genomes.
15 mins – machinery for chromosome synthesis is done by now to mark early/late boundary.
35 mins – “late” phase proteins expressed to begin capsid assembly – cell lysis follows by lipases
• Burst size is the number of virions produced from an infected bacterium (can be >200).
• EM microscopy, ELISA, western blot and PCR measure viral quantity, but not infectivity.
Plaque Assay – 10-100 viruses mixed with ~107 bacteria for 5 mins show plaques after 24 hours.
–Uninfected cells divide every 45 mins to form lawn – (infection cycle is ~50 mins).
–Does not measure amount, but amount needed for productive infection (PFUs).
Phage Lambda – dsDNA 48,514 bp – 12 unpaired on each end – >50 genes arranged by function
–Binds to maltose transport protein to infect – resistant E. coli cannot use maltose.
–Icosahedral, short tail and linear dsDNA with “cohesive” due to complementarity.
–Ends are paired at cos site to form circular DNA that is resistant to exonucleases.
–Immediate early genes – pR and pL promoters – yield short mRNAs and few proteins.
–Delayed early genes – alter machinery – longer mRNAs – proteins for DNA replication.
–Late genes – pR and pL turned off – pR’ active for very long mRNA that encodes
proteins for assembly of capsid and cell lysis.
Virulent phage can only produce a productive infection in cell.
Temperate phage can choose between a productive infection and lysogenic infection.
–Phage Lambda is a temperate virus – chooses path at early phase before DNA synthesis.
–Prefers lytic infection in healthy cells and lysogenic in nutrient deprived.
Lysogeny Features –Viral DNA inherited by daughter cell (lysogens).
–No infection virions (nonproductive). –Repressed capsid proteins needed for lysis.
–Viral DNA retains info for infectivity. –Host cells can grow and reproduce.
• Integration is site specific using integrase at attP site on virus and attB site on bacterium.
–Between genes for galactose metabolism and biotin synthesis, but does not interfere.
• Integrated DNA makes up the prophage (provirus), but is inactive due to cI repressor.
–cI repressor is antigen-specific (does not provide immunity to all viruses).
–Plaques look turbid instead of clear from ~1/1000 cells that become lysogens.
–Damaging conditions also degrade repressor via protease to induce productive infection.
• Transduction of cellular genes can take place from imprecise excision of viral DNA.
• Lysogenic convesion – virulence factors can provide bacteria (and hence virus) advantages.
• Plasmids are 1500-400,000bp of ss- or dsDNA and replicate independently of chromosome.
–Replicons are linear plasmids that autonomously replicate.
–Episomes are plasmids that can integrate into the host chromosome.
–Fertility factor F in E. coli is a large plasmid that can mediate its own transfer.
• Transposons are mobile genetic elements that move within a genome or to other DNA.
–The three classes are insertion-sequence, complex, and phage-associated.
–Insertion sequences have at each end (15-40bp) either direct or inverted repeats.
–Cannot replicate on their own – must be integrate into plasmid or bacteriophage etc.
–Pathogenicity or virulence islands are groups of genes surrounded by transposons.
–G+C content differs from majority of chromosome.
–Often carried by bacteriophages between strains (10,000-200,000bp).
–Often flanked by short direct sequence repeats.
–Staphylococcus aureus (Methicillin-resistance), Enterobacteria (Shiga toxin),
Clostridium botulinum (Neurotoxins), Vibrio cholera (Cholera toxin).
• Transformation is acquisition of new, exogenous genetic material in “competent” cells.
• Conjugation is quasisexual exchange of DNA between bacteria – usually same species.
–One-way transfer from male (w/ plasmid) to female (w/o plasmid) via sex pilus.
–DNA is transferred as a single strand after site-specific cleavage at transfer origin (OriT)
–Takes about 100 mins at 37°C to transfer and is usually interrupted before completion.
–Can incorporate into host chromosome and subsequently cleave again at OriT even after
–F– → F+ with plasmid transfer, F’ if includes host DNA, Hfr if plasmid is integrated.
–Hfr = High frequency of recombination
–Gram(+) bacteria differ – recipient excretes pheromone and donor expresses aggregation
complex to promote the clumping of the two cells.
• Transduction is transfer of DNA via a bacteriophage.
–Specialized if phage transfers particular host genes adjacent to its integration sites.
–Generalized if random host sequences are packaged into capsid (with little viral DNA).
• Homologous (legitimate) recombination occurs between closely related sequences where
one usually replaces the other – requires enzymes produced by rec genes.
• Nonhomologous (illegitimate) recombination occurs between dissimilar sequences where
there are usually insertions or deletions or both – requires site-specific recombination
enzymes, like those from transposons and lysogenic bacteriophages.
Clinical Correlation – Conjugation
Enterococcus faecalis has Vancomycin resistance → natural inhabitant of GI tract – intrinsic
resistance to multiple antibiotics – nosocomial pathogen – contains 25% “foreign” DNA – has 7
integrated phage regions and 38 insertion elements – transfer of vancomycin resistance to
sensitive flora from VRE in animal derived food that was fed vancomycin analog-avoparcin.
Bacteroides have Tetracycline/Erythromycin resistance → Gram(-) – make up 25% of colon
inhabitants – rarely found outside human – resistance elements similar to those in Gram(+).
Clinical Correlation – Transduction
Vibrio cholera has cholera toxin → Gram(-) – genes encoding cholera toxin are carried on
filamentous bacteriophages – transfer of these genes occurs by phage transduction during GI
infection – phage receptor is TCP: toxin co-regulated pilus.
Saprophytes – free living bacteria not associated with disease (most bacteria).
Commencials – bacteria associated with host where both benefit. (most bacteria in host)
Opportunistic – causes disease in a compromised host: immune, physical, or chemical.
Pathogen – capable of causing disease in a “normal host.” Virulence – degree of pathogenicity.
• Two mechanisms of pathogenesis are: 1)invasiveness – damage is due to bacterial growth.
2)toxigenicity – bacterial proteins damage distant from specific site to site of infection.
–Corynebacterium diphtheriae infection in trachea damages all organs with toxin.
• Bacillus anthracis is both invasive and toxic.
• Exotoxins – from both Gram(+/-) – heat labile (proteins) – neutralized by antibodies –
converted to “toxoid” by chemical treatment (formalin) – no fever stimulation – toxic at ug
amounts – toxin alone can cause symptoms.
• Toxins can modify host macromolecules by: ADP-ribosylation, proteolysis, glucosylation,
deamidation, deadenylation.
• Protoxins are stable form that undergo modification to be activated (like proteolysis)
–Diphtheria toxin – A/B (3 domains) – A = catalytic, B = binding and translocation.
Can replace B domain with monoclonal antibody to make immunotoxin that kills tumors.
Classes: Surface-acting toxins, Pore-forming toxins, A/B toxins, Type III and IV secretion.
Diphtheria → 1 case/year in US – killer of young in underdeveloped countries – few ug lethal –
entry by receptor-mediated endocytosis (↓pH) – receptor is heparin-binding EGF –inhibit protein
synthesis (ADP-r-EF2) – treated with antitoxin against B domain (check for hypersensitivity to
horse serum) – vaccines are with formalin-inactivated toxoid or conjugate vaccines.
• Other A/B toxins include: Botulinum, Tetanus, Cholera, Shiga LT
Clostridia → pathogenesis usually exotoxin – saccharolytic or proteolytic – in soil or intestine.
–C. perfingens – histotoxic – invasive – (also novyi and septicum)
–60-90% of clostridial myonecrosis (deep wound to muscle predisposes to infect).
–bacteria may be endogenous or exogenous (not pathogenic to healthy tissue).
–Injury: 1)↓ redox potential (pyruvate→lactate, ↓pH), 2)endogenous proteases.
–C. tetani – tetanus – non-invasive, tetanus toxin – muscle paralysis – proteolytic.
–Injury with mixed soil infection – other bacteria ferment to ↓ redox potential.
–Allows limited growth of C. tetani, but sufficient toxin production.
–Toxin is A:B – A=cleaves membrane fusion proteins, B=binds neuronal cells.
–Singly polypeptide activated with zinc protease by S-S reduction.
–Retroaxonally transported to inhibit release of GABA and Gly in inhibitory
interneuron resulting in spastic paralysis.
–Treated with anti-TT Igs, but only effective before toxin enters the cells.
–Vaccinated using formalin inactivated tetanus toxoid.
–C. botulinum – food poisoning/botulism (6% lethality) – intoxication with A:B toxin
–Toxin activated by Zn protease, is heat labile, inhibits neurotransmitter release.
–Toxin has 7 serotypes (A to G) – anti-BT-A sera neutralizes BT-A, not BT-B-G.
–Botulinum toxins A, B, E are most common natural forms.
–Food-borne, spores in infants, in wounds, can be inhaled in bioterrorism.
–Not contagious, but most potent protein toxin (1ug is lethal).
–Inhibits release of Acetylcholine at presynaptic membrane of peripheral neurons
resulting in flaccid paralysis.
–Treated with anti-A,B,E (army has anti-A-G) – made in horse.
–C. difficile – gastrointestinal disease.
 • About 10x more bacterial cells than human cells.
Staphylococcus → normal flora, skin is barrier, opportunistic bacteria inhabiting alimentary tract
(especially anterior nares), multi-drug resistance, Gram(+), nonmotile, pairs/short chains/cluster,
enterococcus.
–Over 20 different species.
–Direct contact by hands is the most important route of transmission (air-borne possible).
–Limit spread by hospital staff hygiene and disposal of contaminated material.
–Coagulase test separates S. aureus (+) from the rest – epidermidis, saprophyticus etc.
–Survive for weeks in pus/sputum because of tight cell wall structure.
–Techoic acid is required for cell growth (morphogenesis) – stimulates TLRs.
–Envelope: peptidoglycan, techoic acid, protein A (unique to S. aureus), polysaccharides
–Protein A is bound to PG and binds Fc region of IgG (can bind many antibodies)
–Tool for disease diagnosis if bound to agarose beads and antibodies.
–There is no vaccine, but humans are highly resistant if skin not breached (need billions).
–Skin breach is life threatening – multiple virulence factors, antibiotic resistance.
–Conjugate vaccine using P. aeruginosa has only transient immunity in 57%.
S. aureus – facultative anaerobe – makes acetate (O2) or lactate (no O2).
• Enzymes produced are: –Coagulase – clotting of plasma (fibrinogen → fibrin).
–Lipase – helps colonize. –Hyaluronidase – facilitates spreading of infection.
–Staphylokinase – dissolves clots (little contribution to pathogenicity).
–Nuclease – Unique to S. aureus – endo/exo nuclease on DNA or RNA.
• Toxins produced are: –Hemolysins – all β-hemolytic – tissue damage at focus of infection.
–Leukotoxins – 2 protein toxin – attacks polymorphonuclear leukocytes & macrophages
–Enterotoxins (Superantigens) – produced by 1/3 of isolates – heat stable – causes
diarrhea, cramping, nausea, vomiting – in contaminated foods, takes several hours at
room temp. for sufficient toxin – 2-6 hours of symptoms – recovery in 6-8 hours –
intoxication (massive cytokine production) is by enterotoxin, not infection.
–Toxic shock syndrome toxins – associated with tampons – released into circulation –
also a superantigen (bind MHC II & TCR independent of antigen –stimulate 20% Tcells)
–Exfoliative toxins – 2 forms (ETA/ETB) – proteases – lysis of intracellular attachment
between cells of epidermis (Scalded Skin Syndrome – has “Nikolsky sign” – referred to
as Ritter’s Syndrome or Lyell’s Syndrome in newborns or young infants).
• Disease are: ***refer to slide.
• Treatment procedures are:
–Drainage of wound – removal of foreign objects – antibiotic therapy.
–Test for sensitivity → (penicillinR(75%) → methicillinR(10%) → vancomycin)
–Methicillin resistance is due to mutation in PBPs.
–Vancomycin resistance from long treatment → changes in cell wall, not Enterococcus.
• Vancomycin resistant Enterococcus if difficult to treat and life-threatening
–Enterococcus – normal non-aggressive flora – nosocomial pathogen if compromised.
–Plasmid-mediated – VanH reductase (pyruvate→lactate) & VanA ligase (→D-ala-D-lac)
–Vancomycin normally binds D-ala-D-ala, but cannot bind D-ala-D-lac.
S. epidermidis – Coagulase(-) – low virulence – nosocomial from surgery (binds to plastic
catheters etc.) – problem treatment from multi-drug resistance.
–antibiogram (analysis of antibiotic sensitivity locally)
S. saprophyticus – Coagulase(-) – UTI from binding to cells in urinary tract.
Streptococcus → normal flora – used in industrial and dairy – Gram(+) – nonmotile,
nonsporulating – no catalase – hyaluronic acid capsule – needs complex medium – facultative
anaerobe and some obligate anaerobes, divide in one plane (pairs or chains) – central depression
in colony – names based on cell wall components (Lancefield typing) – clinically significant are:
Group A – S. pyogenes (chains) Group B – S. agalactiae
Group D – Enterococcus faecalis, S. bovis (nonenterococcus)
No Lancefiled group = Viridans, S. pneumoniae (pairs), Anaerobic streptococci.
• α-hemolysis – Group B S. pneumoniae (aerobic)
β-hemolysis – Group B S. pneumoniae (anaerobic) Group A S. pyogenes
γ-hemolysis – Group B some Group A
Group A – acute
• Streptococcal pharyngitis – red/swollen mucous membranes, fever, exudates, tosilitis.
• Scarlet fever – s. pharyngitis, erythematous punctiform rash (not on palms, soles, mouth).
• Impetigo – infection of superficial layers of skin in children.
• Erysipelas – infected skin/subcutaneous, edema, advancing induration with distinct border.
• Endocarditis – streptococcal bacteremia allows access to heart tissue, particularly valves.
• Streptococcal toxic shock – focal infection, bacteremia, hypotension, 2 or more of:
ARDS, renal impairment, liver abnormality, coagulopathy, rash w/ soft tissue necrosis.
Group A – late sequelae (does not occur with S. pneumoniae)
• Rheumatic fever – after respiratory infection, hypersensitivity, antigen against heart tissue:
fever, polyarthritis, and carditis – occurs 1-3 weeks after infection – attack rate is <1%.
• Glomerulonephritis – after pharyngeal or cutaneous infection, antigen-antibody complexes
in glomerular basement membrane: fever, blood in urine, edema, hypertension, ↑ BUN.
Group A – Antigenic Structure
• R and T proteins (markers) – M proteins (virulence factor, anti-phagocytic property) –
lipoteichoic acid (attachment), hyaluronic acid capsule (connective tissue cross-reaction),
antigenic mimicry (all types of muscle/neuronal tissue cross-reaction).
–Capsular polysaccharides → anti-phagocytic, major virulence factor in S. pneumoniae.
–Uncapsulated bacteria are avirulent.
Epidemiology
• Group A – 15-20% nasopharynx – peaks at age 6 and 13 – late winter, early spring.
–spread by respiratory droplets/fomites – follow varicella, burns, wounds, chronic illness.
• Group B – 15-20% nasopharynx – 15-40% vagina → 40-70% newborns (1-2% disease).
–2-8% mortality in full-term infants (up to 30% pre-term), pneumonia in the elderly.
• S. pneumoniae – 20-40% nasopharynx – infects only humans.
• Enterococci – antibiotic resistant nosocomial pathogens – advantage during heavy use.
• Infections more frequent at age extremes – pre-school kids get skin infections late summer or
early fall – medical students get around 1st exams or after Strep lab.
Extracellular Enzymes and Toxins – degradative enzymes help spread and pyrogenic exotoxins
trigger a non-specific cytokine production – (most antibodies don’t protect host).
• Leukotoxins – Streptolysin S (O2 stable hemolysin), Streptolysin O (O2 labile NADase)
• Hyaluronidase – host connective tissue and capsule. • Streptokinase – fibrin lysis.
• Streptodornases A-D – DNases (B,D have RNase as well). • Protease
• Pyrogenic exotoxins SPEs A, B, C – superantigens, non-specifically binds MHC II and Vβ
of T cells, cytokine production, bacteriophage encoded (and B, C, F, G), necrotizing fasciitis.
Pathogenesis
• Soft tissue infections resulting in purulent lesions.
• S. pyogenes and S. pneumoniae may infect after change in flora or with viral infection.
–Predisposition to S. pneumoniae → alcoholism, age, splenectomy, chronic cardiac,
pulmonary, renal disease, sickle cell anemia, leukopenia, myeloma, cirrhosis, diabetes.
• Most associated with pharyngitis or bacterial pneumonia.
–Present with ↑ temp, ↑ heart rate, ↓ blood pressure, swelling and erythema.
–Can also cause sinusitis, otitis media, mastoiditis, empyema, joint and bone infections,
necrotizing fasciitis, myositis – endocarditis and meningitis are less frequent.
• Pyrogenic toxin A is associated with scarlet fever.
Other Streptococci
• Group C and G – similar spectrum to A and B, but less likely
• Group D – opportunistic enterococci – S. bovis associated with bowel disease.
• Viridans – normally inhabit oral, GI, urogenital tract – endocarditis, dental caries.
• Anaerobic – normal flora contribute to mixed infections.
Defenses → non-specific mucociliary movement cough, sneeze, and growth of normal flora, or
type specific antibodies to M proteins and capsular polysaccharides in S. pneumoniae.
–vaccines are polyvalent and there are too many M protein types for vaccines.
Treatment
• Penicillin is the drug of choice, but resistance is on the rise.
–Can use Erythromycin, Tetracycline, Clindamycin. (are also Bacitracin sensitive)
• Prophylaxis done for pregnant women with preterm labor etc.
• Group D infections require synergy between β-lactam to facilitate entry of aminoglycoside.
–Resistance from conjugation of plasmids/transposons, transduction, altering PBPs.
• Protein C (anticoagulant) helps by interrupting several pathophysiologic pathways of sepsis.
Enterobacteriaceae
• Gastroenteritis – incubation 12h to days.
• Food poisoning – GI symptoms within a few hours of eating.
• Diarrhea - >300g stool/day with ↑ liquidity and frequency.
–Secretory – water and ion loss, no damage.
–Malabsorptive – damage to mucosal cell → impairs water uptake.
• Desentery – multiple, bloody, mucoid stools.

Salmonella
• S. enterica is most common human isolate –serovariant is S. typhimurium. (0.8-3.7million/yr)
• Gastroenteritis is self-limiting, while systemic infection causes typhoid fever (humans only).
• Contaminates food and water with inhibitory dose (ID) or 10,000 (25%).
–Survives stomach acid to colonize small intestine by entering through M cells –
symptoms at 12-48hrs last 3-4 days → nausea, vomiting, cramps, diarrhea, fever <102°F
• S. typhimurium causes rearrangement and disruption of normal M cell membrane to destroy
these cells and neighboring enterocytes to make hole and gain access to lamina propria.
• Two Type III pathways mediate Salmonella virulence:
–SPI-1 – required to translocate effectors across plasma membrane.
Sops and Sips – ruffling using Rac, filopodia (Cdc42), crosslink actin (Rho, GTPases)
–SPI-2 – required for intracellular survival important for systemic infections.
–translocates effectors across vacuole containing Salmonella (SCV).
–maintains SCV integrity and inhibits SCV fusion with lysosomes.
• Early stages of typhoid fever are like gastroenteritis – fever, endotoxemia, bacteremia etc.
–hemorrhage fever can last for about 30 days (20%).
Shigella
• Invades colonic epithelium for bacillary dysentery.
• Five Invasion protein antigens are virulence factors → IpaA,B,C,D and IpgD
–Body makes antibodies to these antigens after Shigellosis.
–IpaB-IpaC complex – binds a5b1 integrin – mediates ruffling, actin polymerization,
internalization, and pore formation.
–IpaB – binds CD44.
–IpaC – activates the GTPases Rac and Cdc42.
–IpaA – bind vinculin at base of phagocytic structure→ induces F-actin depolymerization
–IpgD – associates with IpaA after bacterial infection.
• Internalized in large vacuole, but replication begins when bacterium escapes the vacuole.

Salmonella
–Diarrhea, gastroenteritis
–Typhoid, enteric fever (typhi)
–Broad host range (except typhi)
–Replicates in vacuoles
–Motile, flagella
–Poultry, eggs, immuno-suppressed
–2, type III systems (uptake, spread)
–High ID (106–108)
–Inflammation/prostaglandins
Shigella
–Diarrhea (sonnei, flexneri)
–Dysentery (dysenteriae)
–Limited host range
–Lyses vacuole
–Non-motile, uses actin inside cell to move
–Children, daycare
–type III system (bacterial uptake, remains localized)
–Low ID (10-100)
–Inflammation/Shiga toxin
Escherichia coli
• Predominately facultative anaerobe, Gram(–) rod, motile, 90% lactose(+), 99% indole(+) –
in colon within a few hours after birth.
–Kauffman (1944) serotyping uses antibodies that agglutinate bacteria:
–O = somatic antigen – LPS side chain. –H = flagellar antigen.
+
–K = capsular antigen, H polysaccharide. –F = fimbrial antigens (proteins).
• Normal E. coli can cause infections in immuno-suppressed or when GI barrier is breached.
• Pathogenic E. coli cause: UTIs, Sepsis/meningitis, Enteric diarhheal disease (6 known types).
–Uropathogenic (UPEC) – most from stool – periurethral/vaginal areas (90% of UTIs).
–Bacteria escape low pH by residing in cells → bladder responds by exfoliation.
–Catheters predispose (within 3-4days) – Bacteriuria if >105cfu/ml ↑ to bladder.
–P (Pap) pili bind to glycoplipids on RBCs and kidney cells → Pyelonephritis.
–Type I pili (FimH, adhesin) bind uroplakins in bladder mucosa → Cystitis.
–Type I fimbriae, pili are mannose sensitive.
–Neonatal Meningitis – 80% synthesize K1 capsular polysaccharide, antiphagocytic,
resistant to complement – 20-40% colonic flora.
–K1 = homopolymer of sialic acid – antigenically like neonatal neuronal tissue.
–Chemically same to capsular polysaccharide of N. meningitidis Group B.
–Bacteremia → 5% <103/ml< 55% – (S. pneumonia has 4% <100-500/ml< 86%).
• Properties determining disease potential are: Adherence, toxins, ability to alter host cell,
ability to invade and replicate, capsular material, ability to capture iron from host proteins,
resistance to normal flora, genetic flexibility (transposons, path. islands, plasmids).
–All E. coli causing diarrhea have at least one plasmid – transposons (ST), phage (Shiga).
• ETEC (Enterotoxigenic) – travelers diarrhea, LT & ST – enterotoxin production – fimbriae
are plasmid encoded – high infectious dose of 108 – mostly during warm, wet months.
–Colonize small bowel → abrupt onset, watery, no blood, hydration maintained.
–Shorten illness with cipro-, nor-, and o-floxacin antibiotics – diagnose w/ assays/probes.
–Labile toxin (LT) – 80% like cholera toxin – has 1 A catalytic and 5 B binding subunits.
–B binds GM1 → A then ADP-ribosylates Gs → ↑cAMP → CFTR ↑Cl secretion
and ↓NaCl absorption → watery efflux, osmotic diarrhea.
–Stable toxin (ST) – monomeric, multi-Cys – encoded on plasmids/transposons.
–STa (18-19aa) → ↑cGMP → CFTR ↑Cl secretion → osmotic diarrhea as w/ LT.
–mimics guanylin (15aa) involved in gut homeostasis.
• EPEC (Enteropathogenic) – infants diarrhea (rotavirus), attaching-and-effacing lesion –
intimate adherence & membrane signaling – cytoskeletal changes – pedestal-like structure –
actin polymerization – high inf. dose of 108-1010 – mostly <2yrs age in developing countries
–In fecal-oral, water, food, fomites → still outbreaks in daycares.
–Pathogenesis – 1)local adherence → with plasmid encoded bundle forming pili (bfp).
2)signal transduction → Ca2+/IP3 → Pi of myosin light chain → PKC → ↑ permeability
of tight junctions → polymorphonuclear migration → ↑ NF-κB, inflammatory response.
3)intimate adherence → mediated by intimin membrane protein from eae gene → binds
to Tir by type III secretion system → Pi of Tir for EPEC, but not for EHEC.
–Fluorescent actin staining (FAS) is diagnostic → EPEC(green), DNA(blue), Actin(red)
–Shiga(–), EAF(+) – atypical strains of EPEC (EAF(–)) implicated in outbreaks.
–Rac, Rho, Cdc42 not involved in pedestal – WASP-Arp2/3 complex as part of base.
• EHEC (Enterohemorrhagic) – HUS, Shiga-like toxin (Stx) expression – intimate
adherence & membrane signaling – in cattle intestines – transmitted by food, water, person-
to-person – low inf. dose of 100-200 – cramps, watery then grossly bloody diarrhea, no fever.
–Hemorrhagic colitis associated with undercooked hamburgers (O157:H7).
–Sporadic HUS associated with fecal cytotoxin (Shiga-like).
–AB5 (A=catalytic, B=binding) → receptor is globotriaosylceramide or Gb3 →
remove adenine from 28S rRNA of host → toxic to endothelial cells, renal cells,
with contributions of LPS, cytokines → inflammatory response.
–can be neutralized with antibody to Shigella dysenteriae 1 toxin.
–Renal failure, thrombocytopenia, microangiopathic, hemolytic anemia – hemorrhage and
edema of lamina propria, thumbprinting pattern in barium enema, neutrophil infiltration.
–Treatment with antimotility drugs (loperamide).
• EIEC (Enteroinvasive) – invasive like Shigella – intracellular invasion – non-motile,
lactose(–), mistaken for and related to Shigella biochemically, genetically, pathogenetically –
watery diarrhea followed by stools with blood/mucus – infectious dose higher than Shigella –
transmit by food, water, person-to-person – ulceration of colonic mucosa.
–Penetrate epithelium → vacuole lysis → intracellular multiplication → moves through
cytoplasm → invasion into adjacent cells.
• EAEC – enterotoxin production – aggregative adherence and delivery of cytotoxin.
• DAEC – associated with elongated microvilli.
CAMPYLOBACTER/HELICOBACTER
• Spiral – Gram(–) – low GC content – cannot ferment/oxidize CHOs – diarrhea – gastric ulcer
Campylobacter
• Can grow at 42°C – microaerophilic – motile (single flagellum at one or each pole) –
infectious dose = 800-106 (500/drop) – found in 50-100% of supermarket chicken (C. jejuni).
• Incubation for 1-7 days with onset at 2-4 days – multiply in both small & large intestine.
–GI distress (24h), diarrhea, pain, fever, nausea, vomiting, bloody stool.
–Inflammatory response similar to ulcerative colitis.
• 10 O-serogroups are associated with 70% of human infections.
–10-20% cause relapsing colitis that mimics Crohn’s disease.
–Guillain-Barre syndrome 2-3wks later – demyelinating disorder.
–usually w/ virus/vaccine (measles, mumps, rubella, V-Z, vaccinia, swine influenza
• 2,000,000/yr in US – (3-14% diarrheal disease in developing countries) – most in summer
• CDT (cytolethal distending toxin) interrupts cell cycle progression.
–Genes also present in Shigella dysenteriae and E. coli.
• Treatment reserved for: ↑fever, bloody stool, pregnancy, >1wk, HIV, immuno-suppressed
–Drugs of choice: erythromycin, fluoroquinolones, tetracycline.
–↑ resistance to fluoroquinolones with use of enrofloxacin in food.
–Vertical transmission from gut, transformation, site specific integrase and
inverted repeat sequences.

→ Foodborne infections: Campylobacter > Salmonella > Shigella > E. coli O157:H7 > Yersinia

Helicobacter pylori
• Microaerophilic – multi-polar flagella – urease – in mucus layer overlaying gastric mucosa.
–No invasion, but motility important to swim below lumen at ↑pH (buffered by urease).
• Small genome (1.67Mb) → different genetic fingerprints in each individual.
–Different genes, but same proteins – (3rd base wobble, inversions, translocations).
–Mixed infection uncommon, but rather incoming contributing to colonizing diversity.
–Excision of cag pathogenicity island → horizontal transfer of new genes.
• 50% of humans infected – 90-95% of peptic ulcers – 70-80% are asymptomatic – associated
with chronic superficial gastritis and development of gastric carcinoma and lymphoma.
• Pathogenicity → Adheres to epithelium below mucus to replicate.
–BabA binds to Lewis b blood group antigens
–LPS has structures identical to fuscosylated Lewis x and y blood group antigens.
–NAP (neutrophil activating protein) – recruits neutrophils to infected area.
–VacA – disrupts cytoskeleton/vesicle trafficking, vacuole formation – gastric erosion.
–CagA – cytotoxin (VacA) associated gene on pathogenicity island for type IV secretion.
–Cag+ strains are strongly correlated with peptic ulcers and cancer.
–Inflammatory infiltrates are: neutrophils, lympocytes, eosinophils.
• Acquired at childhood and same organism can persist for decades.
–Families are often colonized with the same strain – (unknown mode of transmission).
• Diagnosis with: phase contrast microscopy on fresh biopsy – urea breath test – antibodies –
enzyme immunoassay → 96% sensitivity and 96% specificity.
• Treatment: Dual – (H+ pump inhibitor, amoxicillin or clarithromycin), Triple – (bismuth,
metronidazole, tetracycline) → 4% recurrence after eradication or 80% without eradication.
Bacterial Interactions with Macrophages
• Alveolar, Histiocytes, Kupffer, Mesangial, Microglial, Osteoclasts.
• Macrophages are accessory cells in lymphocyte activation.
–Effector cells in cell-mediated immunity and also participate in humoral immunity.
• Recognition → Uptake → Maturation → Killing → Antigen presentation
• Recognition uses pattern recognition receptors (PRR’s) → LPS (Gram–), LTA (Gram+).
–Plasma-derived (collectins, pentraxins, complement) or membrane-derived (C-type
lectins, Leu-rich proteins, scavenger receptors, integrins).
–Intracellular pathogens may recognize multiple receptors whereas extracellular
pathogens avoid recognition-capsules.
• Uptake involves actin polymerization and depolymerization and can be active or passive.
–Effectors can modulate host – TTSS (Salmonella), Coiling phagocytosis (Legionella)
• Maturation involves budding and fusion with last step being phagosome-lysosomal fusion.
–State defined by membrane markers – microtubules facilitate movement toward nucleus.
–pH progressively drops until fusion with lysosome.
–Organisms can alter fate of phagosome, but activated macrophages are more resistant.
–Survive in phagolysosome → Coxiella (accelerate maturation to phagolysosome)
–Escape phagosome to cytosol → Rikettsia, Shigella, Escherichia coli, Listeria
–Cell-to-cell spread with Shigella and Listeria
–Modulate endocyte pathway (arrest at early stage)→Mycobacterium, Salmonella
–No H+ for Mycobacteria – survive H+ for Salmonella (spacious vacuole).
–Alternative membrane trafficking → Legionella, Brucella, Chlamydia
–No interaction with phagosomal pathway, but with ER and Golgi.
• Killing is done using products made by phox (NADPH Oxidase) and iNOS.
–Superoxide, hydroxyl radical, H2O2, hypochlorite - & - NO, NO2, HNO2, peroxynitrite
–Inhibition of DNA, lipids, Fe-S proteins, thiols.
–Defensins, lysozymes, hydrolytic enzymes → ion-perm. channels, cell wall degradation
–Also secrete an array of cytokines to recruit immune system:
–IL-1 → activates endothelium, lymphocytes, local tissue destruction, fever, IL-6.
–TNF-α → activates endothelium, ↑ permeability, IgG, complement, fever, shock
–IL-6 → activates lymphocytes, ↑ antibody production.
–IL-8 → chemotactic factor recruits neutrophils, basophils, T-cells to infection.
–IL-12 → activates NK cells, induces differentiation of CD4 T-cells to TH1 cells.
–Detrimental responses are: tissue injury, fever (IL-1 & TNF-α), chronic inflammation,
autoimmunity, “Trojan Horse” effect to disseminate pathogens.

• Macrophages are major players in innate immunity.

• Phagocytosis is a multi-step process – numerous cytotoxic activities and products.
• Intracellular pathogens alter phagosome maturation.
Mycobacteria: Tuberculosis and Leprosy
• Tuberculosis (M. tuberculosis), Leprosy (M. leprae), Pulmonary disease (M. avium).
• Weakly Gram(–), non-motile, acid fast, aerobic, non-sporulating rods, mycolic acid in wall.
–Resistant to disinfectants, detergents, common anti-bacterials, and stains.
–Cell wall is 60% dry weight, hydrophobic, impermeable, and involved in virulence.
• Mycobacterium tuberculosis is spread by respiratory droplets (1-3 bacilli) and survive in
unactivated macrophages – symptoms are primarily due to host response.
–Human is only reservoir (2 mil in world) –leading cause of death by microbe and in HIV
–Mostly infected in Africa > Asia > South America etc. – (10% annual risk with HIV)
–Steady ↑ in incidence due to: HIV, overcrowding, poor TB programs.
–Initiates in lungs before spread to whole body – delayed-type hypersensitivity (Type IV).
–Acquired immunity halts bacteria in 3-6wks – 5% w/ acute disease within 1-2yrs
–Latent infection → granuloma, controlled growth, lifelong noncontagious carrier
–Immuno suppression induces rapid growth from latent foci – (TNFα, INFγ, iNOS)
–10% lifetime risk if healthy – 10% annual risk if compromised.
–Mantoux test cannot establish presence of active disease.
Active Latent
–Cough –No symptoms
–Weight loss –Do not feel sick
–Highly infectious –Non-contagious
–PPD+ skin test (Mantoux) –PPD+ skin test (Mantoux)
–Abnormal X-ray/sputum test + –Normal X-ray/sputum test
–Daily antibiotic (or 2x/wk), isoniazid, –Standard isoniazid treatment
ethambutol, rifampin, pyrazinamide, streptomycin
–Prevention with DOTS, BCG vaccine (live vaccine against overt disease, not infection)
• Mycobacterium leprae manifestations depend on immune status – spread person-to-person or
through respiratory secretions.
–Tuberculoidal leprosy → strong cell-mediated and weak humoral response.
–Lepromatous leprosy → strong humoral and weak cell-mediated response.
–Abundance of bacilli in macrophages and Schwann cells of peripheral nerves.
–6 million cases in world – common in Africa/Asia, but rare in US
Tuberculoid Lepromatous
–Few erythromatous plaques –Many erythromatous plaques
–Peripheral nerve damage/sensory loss –Extensive tissue damage, diffuse
enlargement of nerves involvement w/ little sensory loss
–Few acid-fast bacilli –Numerous acid-fast – skin lesions
–Not very infectious –Highly infectious
–Reactive to lepromin –Not reactive to lepromin
–Dapsone alone or with rifampin –Dapson, clofazimine, rifampin
–Recommend lifelong treatment to prevent relapse – (no multidrug resistance reported).
• Mycobacterium avium complex from common isolates in water and soil – often in HIV
patients – acquired by ingestion, but not person-to-person – disseminated infection.
• Mycobacterium bovis – TB in cattle – can be highly virulent in man – from unpasteurized
milk or dairy products – inhaled organisms cause disease indistinguishable from tuberculosis.
• Mycobacterium marinum – opportunistic – associated with skin lesions – tuberculosis-like
disease in fish and frogs – commonly obtained from swimming pools and hot tubs.
Legionella
• Gram(–) rod (unencapsulated) – motile, polar flagella – aerobic – poor Gram stain-fuschin –
need complex medium (BCYE), L-Cys and Fe – energy from AAs (not CHOs) – 39 species.
• Legionella pneumophila – facultative intracellular parasite in phagocytes that resists killing
by active O2 and releases a variety of cytotoxins, hemolysins, proteases, endotoxins, lipases.
–Legionaire’s disease – acute pneumonia → 10-20% fatality – 25% nosocomial
–2-10 day incubation – headache, muscle pain, fever, dry cough, hard to breath
–Can progress to multi-organ disease (GI, CNS, liver, kidneys).
–Pontiac fever – acute influenza → symptoms within 12hrs and persists 2-5 days.
–Fever, chills, malaise, headache – no pneumonia – ↓severity –minimal morbidity
–14 serological types based on OMP’s + LPS (serogroup I is major cause of disease).
–In soil and water (natural or man-made), but not part of normal bacterial flora.
–Transmitted by inhaled aerosols, not from water or person-to-person.
–Risk factors: age, male, surgery, bronchitis, cirrhosis, ↓ renal, smoking, immuno-comp.
–Disease rarely spread past lungs → destructive pneumonia obliterates air spaces.
–Influx of monocytes, PMN’s, antibodies, lymphocytes – IL-1 (fever), TNF-α
(systemic symptoms) – activated phagocytes restrict multiplication.
–Diagnosis effective using microscopy with DFA – culture is slow and antigen unreliable
–Treat with azithromycin or levofloxacin in hospital or for immuno-compromised.
–Erythromycin or tetracycline if from community and no therapy for Pontiac fever
–Prevention by H2O treatments: hyperchlorination, superheating, identify infected supply
Pseudomonas aeruginosa
• Gram(–) rod (polysaccharide capsule) – motile, polar flagella – ubiquitous in water and soil –
opportunistic nosocomial pathogen – resistant to chemical disinfection – strongly hemolytic
– produces to pigments pyoverdin and pyocanin – is oxidase(+).
• Can grow at 42°C on simple medium and uses CHOs.
–Oxidizes glucose, xylose, fructose, galactose, but not lactose or maltose.
• Pathogenesis: adhesins (pili/non-pilin) – proteases (elastase & alkaline) – endotoxin (lipid A)
– exotoxins (ExoA,S,T, others) – hemolysins (phospholipase, rhamnolipid, etc.) –
polysaccharide capsule (alginate coat) – pyocyanine and pyochelin (make O2 radicals).
• Prefer moist environments (sinks, toilets, dialysis equipment, catheters, respiratory devices).
• Colonizes → respiratory and GI tracts – burn/trauma wounds – contact lenses.
–Infections → pulmonary, skin, urinary tract, ear, eye, bacteremia and endocarditis.
• Diagnosis is most effective with culture → size, pigmentation, hemolytic activity, odor.
• Treatment with combination of antibiotics (strains vary in sensitivity).
–Tobramycin + antipseudomonal β-lactam (azlocillin, piperacillin, ceftazidime).
–Oral quinolones (ciprofloxacin) in chronic or mild infections.
Burkholderia
• B. cepacia → colonize moist surfaces (UTI’s with catheter, septicemia with IV’s, respiratory
infections with CF or CGD) – low virulence – sensitive to trimethroprim-sulfamethoxazole.
• B. pseudomallei → saprophytic-soil and water – opportunistic, but ↑ infectious – colonize
asymptomatically – cutaneous infection, fever, lymphadenitis – mild bronchitis to necrotizing
pneumonia – some chronic pulmonary – trimethroprim-sulfamethoxazole & cephalosporin.

• Nosocomial = not present at admission (3-5% w/ 90% bacteria) –Community = 48hr before adm.
***Dr. Zahrt, 10/15/03, p.14-15 for rest of stats.
• Man is the only known reservoir for Haemophilus & Bordetella → immunization can control
Haemophilus
• Small Gram(–) rod – facultative anaerobe – requires only one or both of Factors V and X.
–X-factor → heat stable, protoporphyrin IX (hemin precursor).
–V-factor → heat labile, nicotinamide mononucleotide (NAD presursor).
–H. influenzae need both V and X, whereas H. parainfluenzae need only V.
• Haemophilus influenzae – isolated in 1892 (Pfeiffer) and erroneously thought to cause flu.
–Most important human pathogen among Haemophilus - usually associated with disease.
–Isolated from healthy upper respiratory tract (most not encapsulated nor virulent).
–Serotyped according to polysaccharide in capsule.
–Serovar b (Hib) unique w/ pentoses in capsule – cause most invasive infections
–Transmitted via respiratory tract from active, recovering, or carriers.
–In nasopharynx is asymptomatice, but bad in sinuses, middle ear, bronchi
–Virulence due to invasion in blood (expression of capsule).
–Primary cause of meningitis under age 1,
–More than N. meningitidis or S. pneumonia.
–↓ incidence with ↑ antibody – maternal Ab protect <3mos. - ↑risk <3yrs.
–1st generation vaccines were purified capsular polysaccharide (PRP).
–90% effective >24mos. – ineffective <18mos.
–Problems: Poor antigens, T-independent Ab, poor memory.
nd
–2 generation vaccines are PRP conjugates.

Bordetella
• Gram(–) coccobacilli (pleomorphic on subculture) – strict aerobes.
–Disease are: whooping cough (B. pertussis), mild infection (B. parapertussis),
respiratory disease in animals (B. bronchoseptica).
• B. pertussis differs with respect to others by production of pertussis toxin – highly infectious
with >90% unimmunized households infected (asymptomatic carrier → unvaccinated child).
–Vaccine→formalin inactivated whole cell (DTP) –effective, but locally react due to LPS
–local reactivity associated with encephalopathy.
–Adults contract the disease, but it is not recognized as pertussis.
–Non-invasively colonize ciliated cells of upper respiratory tract (tropism) – release toxin.
–Acquired through respiratory droplets → symptoms begin within 10 days.
–3 stages of infection:
–Catarrhal – 1-2wks – mild infection (uncomplicated).
–Paroxysmal – 1-6wks – cough, hacking 15-20s, mucus/vomiting final inspiration
–Convalescence – several months – persistent coughing.
–Pertussis toxin→ 6 noncovalent subunits (A:5B) – A = catalytic (S1), B = binding (S2-5)
–ADP-ribosylates (transferase) Gi protein to negatively regulate (↓cAMP)
–Treamtment is erythromycin to eliminate within 3-4 days.
–Also administered to siblings of patient.
–Prevention via vaccines→ (DTP) Formalin, (DTPa) Component = chemically toxoided PT
Anaerobic Infections
• Anaerobic bacteria found in – breast (85%), pneumonia (80%), necrotizing fasciitis (75%),
bacteremia (10-20%) and abcesses – very little in meningitis and urinary tract.
–Abcesses→ 100% periodontal, 95% intra-abdominal, 90% lung, 80% genitourinary, 75% brain.
Genera
–Actinomyces –Enterobacterium –Mobiluncus –Prevotella
–Bacteroides –Fusobacterium –Peptostreptococcus –Propionibacterium
–Clostridium –Lactobacillus –Porphyromonas –Veillonella
• [logCFU/gm] → Stomach= 1-3 Small intestine= 3-5 Large intestine= 10-12
Lactobacilli Lactobacilli Aerobic + Anaerobic
Streptococci microbial populations
Enterobacteriaceae
• Bacteroides Clostridium Fusobacterium Peptostreptococcus
Head and Neck Wounds – trauma GI tract Ocular discharge
Pulmonary Food borne Nonpuerperal breast abscess
Intra-abdominal Lumen of colon Intra-abdominal discharge
Soft tissue Vaginal purulent discharge
• Predisposition factors → disruption of epithelial barrier, compromised blood supply (↓ Eh),
compromised host defense mechanisms (diabetes, alcoholism etc.).
• Pathogenesis – Trauma → Tissue devitalization (↓perfusion) → ↓O2 → ↓phagocytic
activity → enhanced growth
–Alters microenvironment by: ↓pH, hypoxia, fibrin deposition, LPS→PCA-procoagulant
–Virulence factors: Capsule (abscess & antiphagocytic) – Butyrate (cytotoxicity) –
Mesothelial adherence (peritonitis) – Superoxide dismutase/Catalase (O2 tolerance) –
LPS (inflammation) – Volatile short chain acids (altered inflammatory response).
• Aerobic bacteria can participate in microbial synergism with anaerobic bacteria.
–Copathogens – cometabolic dependence – alter microenvironment – transfer factors.
–Synergistic infections → necrotizing gingivitis/fasciitis, aspiration pneumonia, lung
abscess, intra-abdominal (abscess, peritonitis), perirectal, nonpuerperal breast infections
• Clues → foul odor/discharge – tissue necrosis – abscess – gas in tissue – infection after bites
– blackish or red exudate – sulfur granules in discharge – chronic tissue infection – unique
Gram smear morphology – positive Gram smear-negative aerobic cultures.
• Acceptable specimens: Wound/abscess, pus, tissue biopsy, blood and bone marrow, body
fluid (CSF, synovial, pleural), lung aspiration → exceptions are small bowel and stool.
• Unacceptable specimens: Throat/nasopharyngeal, sputum, fecal/rectal swab, voided urine,
vaginal/cervical swabs.
Head and Neck Infection – or – Biliary Track and Intra-Abdominal Infections
Bacteroides spp Fusobacterium nucleatum Prevotella melaninogenicus
Biophila wadsworthii Hemophilus influenza Proteus spp
Citrobacter spp Klebsiella pneumoniae Pseudomonas aeruginosa
Clostridium spp Morganella morganii Serratia marcescens
Enterobacter spp Neisseria spp Staphylococcus aureus
Enterococcus spp Peptostreptococcus magnus Staphylococcus epidermidis
Escherichia coli Peptostreptococcus micros Streptococcus pyogenes
Eubacterium spp Porphyromonas spp Viridans Streptococcus
• ↓Aerobic bacteria from proximal to distal GI, ↑Anaerobic bacteria from proximal to distal GI
• Bacterial growth after surgery jumps up at 2-6 hours.

Clostridial Infections
• Clues to recognize are: source of infection, Gram smear, spores, motility.
• Enzymes and toxins are: lipase, lecithinase, gelatinase, α,β,ε,θ toxins.
• Gas gangrene is a synergistic gangrene that can occur 1-2 weeks post surgery.
–Facultative anaerobe interactions with 80-95% caused by Clostridium perfringens.
–Also caused by C. novyi or C. septicum.
• Clostridium botulinum occurs in infected wounds and releases a neurotoxic protein.
–Toxin is heat labile, found in patient or food – 1ng is fatal – antitoxin only to type E.
• Clostridium tetani survives for years as spores and enters through wounds or trauma.
–Neurotoxin binds gangliosides in CNS – incubation of 1-15 days.
• Clostridium difficile is indigenous colonic flora with volatile fatty acids.
–Growth is deterred from other bacteria - ↑risk of infection with long antibiotic use etc.
–Prevent with microflora supplementation→ Saccharomyces boulardii, Lactobacillus spp
–Diagnose from stool culture, cell toxicity assay, toxin detection, latex test for antigens.

• Anaeobic Lung Infections with aspiration pneumonia, lung abscess, empyema.

–Peptostreptococcus, Bacteroides, Prevotella, Fusobacterium
• Zoonoses are diseases transmitted from vertebrate animals to humans.
• Humans can intrude in on animal-to-animal chain (Tularemia) or transmit the agent to people
or animals → Mycobacterium bovis (cattle TB), Yersinia pestis (plague), Salmonellosis.
• Symptoms depend on portal of entry – inhalation, penetration of skin, ingestion.
Francisella tularensis
• Gram(–) rod – encapsulated – infectious dose = 1-10 bacteria (10-50 aerosolized) –
facultative intracellular parasite. – (possible for biowarfare)
–Type A → fulminant infections/sepsis –Type B → less severe, fever respiratory
• From: rabbits, muskrats, ticks or deer flies (extremely rare in humans).
• Transmitted by: skinning infected carcass, skin penetration, inhalation of dried excreta.
–Most frequent form of transmission is bites from arthropods.
• Vaccine is multiple skin punctures → partial immunity and only large-scale in Russia.
–Treatment: streptomycin, gentamicin, tetracycline (can have relapse with tetracycline).
Yersinia pestis
• Gram(–) rod – Enterobacteriaceae – causes plague – first recorded occurrence of biowarfare.
• Pandemic → Egypt/Ethiopia (542AD, 100mil) –East Europe (14th C., 25mil) –Burma (1890s)
–Endemic in urban rats and wild rodents.
• From: rodents, mice, rats, squirrels, prairie dogs.
• Transmitted by: fleas → Bite infected host → replicates in GI → produce coagulase to clot
→ replication within ingested clot → blockage of GI → regurgitation into wound of another.
–Humans interrupt the natural cycle of Y. pestis.
• Pneumonic plague from inhalation and bubonic plague in lymph node (from flea on skin).
–Black Death = diffuse hemorrhagic changes in skin and cyanosis caused by pneumonia.
• First TTSS (Type III) and toxin w/o B subunit – thermally regulated –virulence determinants:
–1)Pla = plasminogen activator protease (at ↓ temp) – 2)Fraction 1 = inhibits PMNs –
3)pH 6 antigen = adhesin – 4)V antigen (LcrV) = regulates TTSS, needed for Yop
translocation – 5)Yops = prevent phagocytosis → YopE (cytotoxin, Rho, GAP), YopH
(Tyr phosphatase – disrupts signal transduction in mammals).
Bacillus anthracis
• Gram(+) rod – endospore – in soil – death by septicemia – symptoms only hours before death
• From: sheep, cattle, goats, horses, hogs.
• First to have definitive etiology using Koch’s postulates:
–1)Organism in diseased, but not in healthy. –2)Can be isolated and grown in culture.
–3)Isolate can reproduce disease in another. –4)Organism can be isolated from new host.
• 1/yr (past 10yrs) – 18 in 20th century – 10,000 of cutaneous anthrax in Zimbabwe (1978-80)
–Inhalation cases mostly related to woolen workers.
• Cutaneous Anthrax – small cuts – 95% of anthrax in humans – often mistaken for S. aureus.
–Bluish-black fluid in papule (2-5 days) – ruptures for malignant pustule (2-3 wks)
–Most common on hands, forearms and head – Mortality <1% if treated.
• Pulmonary Antrhax – need 8,000-10,000 spores inhaled – incubation 1-6 days.
–Minimal symptoms (2-3 days) followed by respiratory distress, cyanosis, chest pain.
–Widening of mediastinum – pleural effusions – seizures – 50% with meningitis.
–Rapid shock/death (24-36hrs) – Mortality 100% despite treatment.
• Gastrointestinal Anthrax – ingest uncooked meat – incubation 2-5 days.
–Oropharyngeal disease (sore throat, tonsillar ulcer, neck swelling, lymphadenitis, etc.)
–May be dysphagia, poor breathing, nausea, vomiting, diarrhea – Mortality up to 50%.
Bacillus anthracis (cont’d)
• Virulence determinants are:
–Glutamyl polypeptide capsule – interferes with phagocytosis (110kb plasmid)
–Exotoxins (60kb plasmid)
–Lethal toxin – Zn metalloprotease – (A = lethal factor)
–Edema toxin – Calmodulin-dependent adenylate cyclase – (A = edema factor)
–Both share same B subunit = Protective antigen or PA
–PA binds cellular receptor → cleaved → can now bind LF or EF
–PA + LF = lethal toxin –PA + EF = edema toxin
• Vaccine is a filtrate from unencapsulated strain – mostly PA – small amounts of LR and EF.
–Subcutaneous 0, 2, 4 weeks → booster at 6, 12, 18 months.
• Treatment with penicillin or ciprofloxacin → work only on growing organisms, not spores.

Summary – Zoonosis
• Animal to person.
• Entry by:
–Penetration of skin – animal/arthropod bite or abrasions.
–Ingestion
–Inhalation
–Clinical outcome depends on mode of entry.
• Francisella tularensis – multiple modes of entry – low infectious dose.
• Yersinia pestis – bubonic/pneumonic plague – fleas or aerosols – 1st TTSS – toxins.
• Bacillus anthracis – in soil – protein capsule lethal toxin (protease) & edema toxin (cyclase)
Intracellular Pathogens
• Obligate Intracellular pathogen – Coxiella, Rickettsia, Chlamydia, Chlamydophila,
Ehrlichia, Mycobacterium leprae.
• Facultative Intracellular pathogen – Legionella, Enteroinvasive E. coli, Salmonella,
Shigella, Mycobacterium tuberculosis.
• Epicellular – Bartonella, Mycoplasma.
• The more host adapted, the smaller the genome.
Rickettsiae
• Small Gram(–) rod – zoonoses transmitted by arthropods (tick, mite, flea, louse, chigger)
–Exception is Q fever.
–Epidemiology linked to distribution of infected arthropod.
–Spotted Fever Group
–Rocky Mountain spotted fever – R. rickettsii – ticks
–Boutonneuse Fever – R. conorii – ticks
–Rickettsial pox – R. akari – mites
–Typhus Group
–Epidemic Typhus – R. prowazekii – lice
–Murine Typhus – R. typhi – fleas, rats
–Scrub Typhus – O. tsutsugamushi – chiggers
• Pathology includes: 1)endothelial injury, 2)loss of intravascular fluid, 3)low blood volume.
• Rocky Mountain Spotted Fever – Rickettsiae rickettsii – mainly Southeast US (no Rockies)
– Apr-Sep – mostly children - ↑ severe in elders and African Americans w/ G6PD.
–Transovarial transmission → female tick to infected ova.
–Damages blood vessels – invade vascular SM – consume platelets (thrombocytopenia)
–Highly cytotoxic → few accumulate in cell and leave by filopodia to many other cells.
• Rickettsialpox – R. akari – in NY (1940s) – mite-infested mice –fever, rash like chicken pox
• Boutonneuse fever – R. conorii – papular rash – synonyms based on geographic region.
–Mediterranean spotted fever, Kenya tick typhus, South African tick bite fever.
• Epidemic Typhus and Brill-Zinsser Disease – R. prowazekii – significant during war and
disaster – reservoir in human, but spread by lice – becomes latent and can re-emerge later.
–Little cellular pathology → massive quantities accumulate before lysis.
⇒ Enter skin → bloodstream → endothelial phagocytosis → escape → reproduce intracellularly.
–Endothelium in skin, brain, heart, liver, lung, kidneys, gastrointestinal tract.
Ehrlichia
• Inhibition of phagosome-lysosome fusion → lysis of cell and phagosome.
• Ehrlichiosis –Ehrlichia chaffeensis –fever, leukopenia –Lone Star tick –↑risk w/ ↓golf score
Coxiella
• Survival of phagosome-lysosome fusion → lysis of call and phagolysosome.
Chlamydia/Chlamydophila
• Obligate intracellular parasites – cannot make own ATP – chronic infection & atherosclerosis
⇒ Vacuole (dormant) → elementary body → reticulate body development/maturation → release
• ↑ blood vessels, connective tissue, lymphocytes → chronic inflammatory response.
• Antibodies don’t work & vaccines make worse –use tetracycline, erythromycin, sulfanomides
• Chlamydia trachomatis – ocular infections or sexually transmitted diseases.
–Ocular – conjunctiva, cornea vascularized/cloudy (fibroblasts), inward lashes, opaque
–Serotypes D, E, F, G, H, I, J, K
–In Africa, Asia, hot dry climates or with low hygiene.
–Spread by flies, fingers, towels, cosmetics.
–STD – lymphogranuloma venereum, chronic cervicitis, nongonococcal urethritis.
–Serotypes A, B, Ba, C –Spread by sex.
• Chlamydophila psittaci – psittacosis, pneumonia – serotypes L-1, L-2, L-3, unidentified.
–Spread by wild and domestic fowl.
• Chlamydophila pneumoniae – pneumonia, bronchitis, sinusitis – serotype TWAR.
–Atypical – first found in Taiwan – also in Scandinavia, Japan, Panama, North America.
Mycoplasma
• Smallest free-living prokaryotes – no cell wall (Mollicutes or soft skin) – cocci w/ elongated
filamentous forms – fried egg appearance on agar – require sterols for growth (↑ cholesterol
in membrane) – slow growth in vitro – Ureaplasma unique for needing urea to grow
–Surface parasitism → host receptor = sialoglycoprotein/lipid, Mycoplasma adhesin = P1
–Escape immunity with antigenic variation → may be involved in autoimmunity.
• Mostly age 5-9yrs – 8-15% of all school age pneumonia (15-50% adults) – incubation 2-3wk
–Rare pneumonia in infants (maternal antibodies)
• Co-factor in development of AIDS → M. fermentans, M. penetrans, M. pirum
• Treat with tetracylines, macrolides, quinolones – must treat sexual partner for Ureaplasma
• Mycoplasma pneumonia – upper respiratory disease limited to one lower lobe (gradual onset)
–Pneumonia is interstitial or bronchopneumonic.
–Cold agglutinins (Ab to RBCs) – Eaton’s agent (filterable) – grows cell-free (not virus)
• Nongonococcal Urethritis – in men (w/o C. trachomatis) from Ureaplasma urealyticum –
also associated in women with chorioamnionitis, habitual spontaneous abortion, ↓ birth wgt.
–M. genitalium may also play role in male urethritis.
• Salpingitis – M. homonis – in vagina of healthy women – can invade genital organs and
contribute to PID or tubo-ovarian abscesses.
Spirochetes
• Gram(–) – thin, long, helical – motile (endoflagella or axial filament) – reproduce by
transverse fission.
Treponema
• Treponema pallidum – subspecies pallidum (syphilis) / endemicum (bejel) / pertenne (yaws)
• Treponema pallidum-pallidum
–Strict human pathogen – cannot grow cell-free - ↓ biosynthesis – microaerophillic –
sensitive to drying and disinfectants – lacks loop shape.
–Antigens → no LPS, ↑ cardiolipin, glucosaminoglycan in outer sheath, weakly antigenic
–Can survive in blood or plasma >24hrs.
–Hyaluronidase breaks down tissue – fibronectin protects against phagocytosis.
–Primary → local lesions - spread to LNs/bloodstream (1-4wks) – ↑ infectious – painless.
–Secondary → disseminated – flu-like – rash – 2-12wks after 1° – ↑ contagious – painful.
–Tertiary → inflammation – mos./yrs after – not infectious – CNS/cardio, Gummas
–Congenital → vert. trans. – spont. abortion, still birth, premature – 70-100% from 1°
–Treatable with antibiotics – symptoms similar to secondary syphilis.
–Sexual contact (~60%) – transplacental – transfusions – >12mil in world, <105 in US/yr
–Diagnosis by visualization (dark field) or serological tests – culture assays not possible.
–Treatment with penicillin (stage determines dose and duration).
–No vaccine → practice safe sex and treat infected partner.
• Treponema pallidum-endemicum
–Spread person-to-person – 1° oral lesion rare – 2° oral lesions common – rash-gummus
of skin – endemic in Africa, Asia and Australia.
• Treponema pallidum-pertenue
–Granulomatous disease with primary leasion – destruction of skin, LNs, bone
–Endemic in tropical regions → S. America, C. Africa, S.E. Asia
• Treponema carateum – pinta.
–Spread by direct contact with infected lesions – rash may last months-years –
disfigurement from recurrent lesions – prevalent in Central and South America.
Leptospira interrogans
• Hooked at one or both ends – obligate aerobes – 2 flagella at opposite ends – fatty acids and
alcohols as C and E sources.
• Worldwide (rare in US) → common in warm months – also in rats, cattle, and dogs.
• Leptospirosis – from animals via urine-contaminated water → breach mucosa or ingestion.
–Often mistaken for viral infection (subclinical).
–Incubation 1-2 weeks – flu-like for 1 week – found in CSF.
–Second phase for 2-3 weeks → aspectic meningitis, headache, rash, hepatic/renal
–Congenital disease can occur with similar symptoms.
–Diagnosis serology or culture – not effective by microscopy.
–Culture from blood or CSF (0-10 days) – or – from urine (1st week to 3 months).
–Treatment:
–Oral for mild disease → doxycycline, ampicillin, amoxicillin.
–IV for severe disease → penicillin or ampicillin.
–Vaccines for cattle and pets, otherwise rodent control & drainage of contaminated water.
Borrelia
• Weakly Gram(–) – spirochete (larger) – microaerophillic – highly flagellated – linear
chromosome and plasmids – complex nutrient needs.
• Antigenic variation is 103-104/generation using “mini-chromosome” shuttle mechanism.
–Gene conversion is between silent and expressed genes.
• Epidemic Relapsing Fever – Borrelia recurrentis – humans are only reservoir – not
disseminated by louse – associated with overcrowding, poverty, war.
–E. and C. Africa, China, Andes
–Incubation 7 days - ↑ fever, severe headache, muscle pains, weakness (3-7 days) –
milder symptoms redevelop after 1 week (afebrile period). → 1-2 relapses.
–Diagnosis using Giemsa stain – serological tests ineffective due to antigenic variation.
–Treat with tetracycline or erythromycin. –No vaccines → rodent control, insecticides.
• Endemic Relapsing Fever – Borrelia spp. – disseminated infection in ticks (Ornithodorus)
–Most of world, but associated with Western states in US.
–Clinically similar to epidemic version except → 3-4 relapses.
• Lyme Disease – Borrelia burgdorferi – tick (Ixodes sp) – chronic erythematous skin rash and
fever – chronic arthritis from disseminated disease.
–Leading vector-borne disease in US → primarly in NE, upper Midwest, Pacific West
–Reservoirs are mice (larval/nymph) & deer (adult) → ticks transmit to human via saliva.
–Primary stage – incubation 3-30 days – skin lesions (erythema migrans) at infection site.
–Severe fatigue, fever, malaise, muscle pain (lasts 4 weeks).
–Secondary & Tertiary stages – weeks/months after primary – neurological symptoms or
cardiac dysfunction – persistent arthritis.
–Diagnosis by serological tests, ELISA, Western blot – not by microscope or culture.
–Treatment:
–Early infection → oral deoxycycline or amoxicillin.
–Second/third stage → ceftriaxone, deoxycycline or amoxicillin (prolonged time).
–Chronic arthritis → antibiotics not effective.
–Prevent with → protective clothing, deticking, repellants – no vaccine.
Neisseria, Moraxella, Kingella and Eikenella
• Gram(–) diplococci – oxidase(+) – catalase(–).
• Moraxella – conjunctivitis (poor hygiene), secondary respiratory infections, otitis media, sinusitis.
• Kingella – infections of bones, joints, and tendons.
• Eikenella – infections caused by human bites.
Neisseria
• Infection follows mildly symptomatic or asymptomatic nasopharyngeal carrier state.
–↑ carriers in older children/young adults → most epidemics associated with group A.
–Transient bacteremia, fever, malaise (may resolve in 1-2 days).
–Acute bacterial meningitis → chills, fever, servere headache – abrupt/insidious onset.
–Petechiae or purpura on skin (days 1-3 in 30-60%)
• Waterhouse-Friderichsen syndrome – fulminant meningococcemia - ↑ mortality rate
–5-15% of those with meningococcal disease
–Abrupt onset of fever, chills, headache, vomit, muscle ache
–Within hours → apprehension, delerium, purpuric skin lesions, ↓ pulmonary
–Within 24 hours → death regardless of therapy
–Meningococcal meningitis is sporadic with ↑ incidence in late winter/early spring.
• Neisseria meningitis – serogroups defined by capsular polysaccharides (A,B,C,Y,W135)
–Transmitted by respiratory droplets → attaches to non-ciliated columnar via pili.
–Internalized, but remain apically localized → enter bloodstream and cross BBB.
–Local cytokine production, inflammation – lipooligosaccharide is highly toxic.
–Defend with intact pharyngeal and respiratory epithelium & antibodies IgG, IgM.
–Concurrent viral or mycoplasma infection leaves more susceptibility.
–Abs are against surface/capsular proteins –also induced by N. lactamica & others
–IgA induced by other strains to block IgG and IgM (↓ protection).
–Vaccines for all except serogroup B
–Identical to E. coli K1 antigen → homopolymer of sialic acid (on brain cells).
• Neisseria gonorrhea – infect cervix, urethra, pharynx, and conjunctiva → purulent discharge
–Outer membrane proteins: Por (opaque phenotype) – Rmp (blocks Abs to Por & LOS) –
transferrin, lactoferrin, heme, Hb receptors – Por (porin) – LOS (inflammatory response)
– IgA1 proteases (block Fc-mediated functions of antibodies).
–Pili have phase variation (pilin ↔ pilin-expression) and antigenic variation (recomb.)
–Attachment mediated by pili, surface charge/hydrophobicity – GC is autocatalytic.
–Asymptomatic women are reservoir – transmitted almost exclusively by sexual contact.
–Dysuria in both men and women (urethritis)
–Gonococcal proctitis → burning, itching, defecation
–Disseminated gonococcal infection → dermatitis, arthritis, septic joint with effusion.
–Pelvic Inflammatory Disease → endometriosis to salpingitis (f. tubes) to peritonitis
–Pelvic and abdominal pain, fever, chills, cervical motion tenderness
–Complications → tubo-ovarian abscesses, ectopic pregnancy, pelvic peritonitis.
–Ophthalmia neonatorum – eye infection acquired at birth
–Non-specific defense (pH, hormones) – No vaccines
–Most frequent reported infection disease in US, but low in Europe
–Highest rates in women 15-19yrs – men 20-24yrs. → risk from multiple partners
–90% men and <50% women have urethral GC within 5 days.
–Most cases concentrated in SouthEastern states.
Sexually Transmitted Infections
• HIV = >$6.7bil/yr • Other STDs = >$10bil/yr
• New cases per year:
–HPV 5,500,000
–Trichomoniasis 5,000,000
–Chlamydia 3,000,000
–Herpes 1,000,000
–Gonorrhea 650,000
–Hepatitis B 77,000
–HIV 20,000
• High risk for → adolescent, young adult, African-American, gay
• STIs can be → asymptomatic, latent, persistent, recurrent
–Can cause → overt infection, neonatal infection, long-term disease/disability, cancer, death.
Chlamydia trachomatis
Women – cervicitis, urethritis, salpingitis, chronic tubal disease/pelvic pain, infertility.
Men – urethritis.
Neonates – conjunctivitis, pneumonia.
• ↑ in adolescents – usually asymptomatic – most common upper genital tract infection
Neisseria gonorrhea
Women – cervicitis, urethritis, salpingitis, chronic tubal disease/pelvic pain, infertility.
Men – urethritis, arthritis.
Neonates – conjunctivitis, rhinitis, arthritis, sepsis, meningitis, vaginitis.
• Common co-infection with C. trachomatis.
Upper Genital Tract Infection – PID
• Typically polymicrobial → Chlamydia, gonorrhea, facultative anaerobes, anaerobes.
• Abdominal pain, fever, pelvic tenderness, ↑ WBCs
–Late sequelae→ Infertility (10-20%) – Ectopic pregnancy (7-10x) – tuboovarian abscess
Genital Herpes
• Painful labial lesions – latent in dorsal ganglia of sensory nerves – asymptomatic shedding.
• HSV-2 most common (15-20% HSV-1) – No cure – No vaccine
• Neonatal primary infection (30-50%) or from perinatal transmission (3-10%)
HPV – Human Papilloma Virus
• Most common STI in the US.
• Infects basal cells in squamous epithelium of cervix, vagina, vulva, anus, penis.
–Present in >95% of squamous cervical cancers.
–May be etiologic agent in adenocarcinoma of cervix.
• More than 80 subtypes affecting genitalia.
–Type 6, 11 – anogenital warts, rarely oncogenic.
–Type 16, 18, 31, 33, 35 – anogenital squamous intraepithelial neoplasia and cancer.
–Occasionally associated with visible warts.