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Gram Negative Pathogenic

bacteria
Shimelis Teshome (BSc MLS)
Helicobacter
•There are 22 species
•Three species are currently considered to be human pathogens
–Helicobacter pylori (human; no animal reservoir)
–H. cinaedi (male homosexuals; rodents)
–H. fenneliae (male homosexuals; rodents)
–In humans, enterohepatic helicobacters, such as H. canadensis, H.
canis, H. pullorum and H. winghamensis, have been isolated

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Helicobacter cont…

• Enterohepatic helicobacters have been linked to


severe inflammatory lesions in the lower bowel, gall
bladders, and livers of infected humans
H. pylori
• Commonly associated with
Gastritis
peptic ulcers
gastric adenocarcinoma, lymphoma
• Highly motile (polar flagella)
• Young culture spiral shaped
• Old culture assume coccoid shape
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Helicobacter cont…
• Produce abundance urease (isolate which colonize stomach)
• Don't oxidize or ferment CHO
• The principal means of energy production and biosynthesis
is believed to occur via glycolysis and gluconeogenesis
• Microaerophilic and need high CO2
 Pathogenicity
• Virulent factors are responsible for
– Gastric inflammation
– Alteration of gastric acid production
– Tissue destruction

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Helicobacter cont…
Initial colonization is facilitated by:-
A. Blockage of acid production (acid inhibitory proteins)
B. Neutralization of gastric acid by ammonia
C. The bacteria penetrate (active motile) and pass the
gastric mucosa and adhere to epithelia cells (Cork
screw type motility)
D. Localized tissue damage will occur by urease,
mucinase, phospholipase, vacuolating cytotoxins
E. Produces catalase and superoxid dismutase which
prevents intracellular killing

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Entrobacteriaceae
(enteric bacteria)

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Enterobacteriaceae….

• Live in the intestinal tracts of animals in health and


disease.
• Gram-negative, oxidase-negative, rod-shaped, motile by
peritrichous flagella, facultative anaerobes, ferment glucose
producing acid and gas.
• Escherichia, Enterobacter, Klebsiella, Proteus, Morganella,
Providencia, Salmonella, Shigella and Yersinia
• Enterobacteriaceae are distributed worldwide.
– They are found in water, soil , insects, fruits, vegetables, grains,
flowering plants, trees and as normal intestinal flora in humans
and many animals.

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Enterobacteriaceae….
Human Pathogens
• Enterobacteriaceae are divided into pathogens and
nonpathogens based on their ability to cause diarrheal
disease of humans.
– The pathogenic genera were Salmonella, Shigella , E.
coli and Yersinia
• E. coli causes at least five types of gastrointestinal disease
in humans.
– Pathogenicity in E. coli strains is due to the presence of one
or more virulence factors, including
• invasiveness factors (invasins),
• heat-labile and heat-stable enterotoxins, and
• colonization factors or adhesins.

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Feces from humans or animals
containing pathogenic microbes or
their toxins

Food Fluid(milk or
water) Finger

Ingestion of
organism and/or
toxin

Gut

Organism multiply and toxin produced Organism invade or


but infection remains to localized in GIT toxin absorbed

Diarrhea Dissemination

Symptoms of systemic
Pathogen excreted in feces infections
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1. Escherichia coli Infections
E. coli is part of the normal flora of the colon in humans and
other animals
Can be pathogenic both within and outside of the GI tract
The differences in the degree of virulence of different E. coli
strains are caused by
 The individual plasmid and
 Integrated prophage repertoire associated with each strain
E. coli has fimbriae or pili that are frequently
important for adherence to host mucosal surfaces
Different strains of the organism may be motile or non
motile.

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E.Coli Cont…
Clinical significance: intestinal disease
Transmission of intestinal disease is commonly by the fecal/oral
route
At least five types of intestinal infections that differ in pathogenic
mechanisms have been identified
Enterotoxigenic (ETEC)
enteropathogenic (EPEC)
enterohemorrhagic (EHEC)
enteroinvasive (EIEC) and
enteroaggregative (EAEC)
All are basically the same organism, differing only by the
acquisition of specific pathogenic traits
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E.Coli Cont…
Clinical significance: extra-intestinal disease
• The source of infection for extra-intestinal
disease is frequently the patient's own flora
• in which the individual's own E. coli is
nonpathogenic in the intestine.
• However, it causes disease in that individual
when the organism is found in the bladder or
bloodstream (normally sterile sites)

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E.Coli Cont…
Urinary tract infections (UTI):
E. coli is the most common cause of UTI, including cystitis and
pyelonephritis.
Uncomplicated cystitis (the most commonly encountered UTI)
is caused by uropathogenic strains of E. coli
Characterized by
 P fimbriae (an adherence factor)
 hemolysin,
 colicin V and
 Resistance to the bactericidal activity of serum complement.
Complicated UTI (pyelonephritis) occurs in settings of
obstructed urinary flow, which may be caused by
nonuropathogenic strains
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E.Coli Cont…

Neonatal meningitis:
• E. coli is a major cause of this disease occurring within the
first month of life.
• The K1 (capsular) antigen is particularly associated with
such infections.
The most common causes of neonatal meningitis:
• Group B streptococcus, E. coli and Listeria
• The most common causes of neonatal sepsis with or
without meningitis: Group B streptococcus and E. coli
Nosocomial (hospital-acquired) infections:
These include sepsis/bacteremia, endotoxic shock, and
pneumonia.

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2. Salmonella

• Salmonella adopted in honor of Dr. Salmon, who


discovered Salmonella from infected pig in 1885.
• Contaminated animal products
• Salmonellosis - mild
• Typhoid fever – severe
• Normal flora in animals
• A major health problem
Non-typhoidal salmonellosis
– Mainly due to S. Enteritidis, S. Typhimurium
– 1.3 billion cases and 3 million deaths/y
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Salmonella

 Typhoid fever/Enteric fever


– Mainly due to S. Typhi
– >21 million cases and 700,000 deaths/y
 Salmonella:-
Gram negative, facultative anaerobes bacilli, Glucose fermenters,
oxidase –ve, motile (most), non capsulated except, S. Typhi, S.
Paratyphi C and S. Dublin.
 Antigens
A. O (somatic antigen) used for Serogrouping
Represented by letters or numbers
B. H (flagellar) antigen
C. Vi antigens
Found in S. Typhi, S. Paratyphi and some strains of S. Dublin.

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Salmonella
Clinical disease
Salmonella infection results:-
a. Gastroenteritis
b. Septicemia/ systemic infection
c. Enteric fever
d. Asymptomatic colonization
 G/E
Symptoms appear after 6 to 48 hrs
Nausea, vomiting, non-bloody diarrhea, fever,
abdominal crump, myalgias and head ache
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Salmonella
 Septicemia
 Can be caused by all serotype, commonly caused by
S. Choleraesuis, S. Paratyphi, S. Typhi
 Common in children, geriatric patient and in immuno-
compromized patient
 Enteric fever
 Caused by:- A. S. Typhi_ typhoid fever
B. S. paratypi A, B, C- paratypoid (mild
typhoid)
 Bacilli pass lining of SIengulfed by macrophage 
bld  liver, spleen, bone marrow, replicate  gall
bladder and SI  perforation and hemorrhage
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3. Shigella
• Discovered by Japan microbiologist Shiga 100 years
ago
• The genus consists of four species( biochemical,
serology) : S. dysentriae, S. flexneri , S. bpydii, S.
sonnei
• All Cause Shigellosis or bacillary dysentery
• Shigella dysenteriae: causes most serious form of
bacillary dysentery
• Shigella flexneri: most common cause of shigellosis in
underdeveloped countries
• Shigella sonnei: most common cause of shigellosis in
developed countries
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Shigella
Clinical features
Incubation time is 1 to 3 days
Characterized by:-
Abdominal crump, diarrhea, fever
Pus and blood in stool (due to colonic invasion)
Epidemiology
Human is the only host
Transmitted by feco-oral route
Shigellosis is common in communities with low
sanitation and personal hygiene
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Shigella
• 200 bacilli can initiate the disease (contagious)
• Epidemic is common in closed communities like,
daycare centers, nurseries, etc.
 Treatment
Guided by susceptibility tests
Empirical therapy can be initiated with fluroquinolones or
SxT(cotrimoxazole, trimethoprim-sulfamethoxazole)
 Prevention
1. Sanitary control of food and water/personal hygiene
2. Detection of carriers particularly in food handlers
3. Rx of infected individuals

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4. Pseudomonas aeruginosa
Morphology: Gram stain of P. aeruginosa
 Gram-negative rod
 Motile (single
polar Flagellum)
 Some are
encapsulated
 Non fermenative
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Pseudomonas aeruginosa……
 Pathogenesis
It is an opportunistic pathogen
 Need some breach in Io host defense to
initiate an infection
P. aeruginosa has many virulence factors
1. Structural components
2. Toxins
3. enzymes
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5. Vibrio
•Genus Vibrio contains 60 species
•Primarily found in water and cause G/E
•10 species are related to human infections
•V. cholera, V. parahaemolyticus, C.
vulnificus are medically important
General characteristics
Gram negative curved rods, motile (polar
flagella), oxidase positive,
 Grow B/n 14-40oC,
 Grow best at alkaline pH
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Vibrio cholera…….
• Individuals with low HCL are susceptible
• Found in fresh and marine water and associated
with aquatic animals.
• Posses polar flagella, pili

• O polysaccharide in LPS used for serogrouping


• Has over 140 identified serotypes based on O-
antigen(O1-O139)
• Only O1 and O139 are toxigenic(produce cholera
toxin) and cause epidemic Cholera disease
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Vibrio cholera…….
• Vibrio O1 divided into
3 serotypes:- Inaba, Ogawa, Hikojima
Virulence factors (O1, O139)
Cholera toxin:- Hyper secretion of electrolyte and water
 A-B type of toxin
 Encoded on a filamentous phage (ctxΦ) that is capable of
transducing the ctx gene into other cholera strains
Pili:- adherence to intestinal cells and binding site for
phages
Neuraminidase:- cleaves sialic acid from some cell
that can be used as receptor for pili
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Neisseria
Neisseria spp are Gram negative cocci
Neisseria spp Sub divided in to two

1. N. Gonorrhoeae (gonococcus)

2. N. meningitidis(meningococci)

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N. Gonorrhoeae….
 Morphology and physiology
Aerobic Gram-negative diplococci, non spore former,
non motile, oxidase and catalase positive, usually
seen in pairs with adjacent flattened sides
Frequently found intracellularly in polymorphonuclear
leukocytes
Fimbriae, which play a major role in adherence, extend
several micrometers from the cell surface

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N. Gonorrhoeae….
• Possesses a typical Gram-negative outer membrane
composed of proteins, phospholipids, and
lipopolysaccharide (LPS).
• Distinguished from enteric LPS by its
– Highly-branched basal oligosaccharide structure
– The absence of repeating O-antigen subunits.
– Thus neisserial LPS is referred to as lipooligosaccharide
(LOS).
• The bacterium characteristically releases outer
membrane fragments called "blebs" during growth.
– Blebs contain LOS and probably have a role in pathogenesis if
they are disseminated

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N. Gonorrhoeae….
Infections caused by N. gonorrhoeae
• Gonorrheal infection is generally limited to
superficial mucosal surfaces lined with
columnar epithelium.
– The areas most frequently involved are the
urethra, cervix, rectum, pharynx, and
conjunctiva.
• Mucosal infections are usually characterized
by a purulent discharge.
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N. Gonorrhoeae….
• Uncomplicated gonorrhea symptom in the adult male is
– a discharge that may range from a scanty, clear or cloudy
fluid to one that is copious and purulent.
– Dysuria and intense burning and pain upon urination.
– Inflammation of the urethral tissues results in the
characteristic redness, swelling, heat, and pain in the region.
• Endocervical infection is the most common form of
uncomplicated gonorrhea in women.
• Usually characterized by
• vaginal discharge and sometimes by dysuria.
• About 50% of women with cervical infections are
asymptomatic.

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N. Gonorrhoeae….
– In the male, the organism may invade the
prostate resulting in prostatitis, or extend to the
testicles resulting in orchitis.
• In the female, cervical involvement may extend
through the
– uterus to the fallopian tubes resulting in
salpingitis, or to the ovaries resulting in ovaritis.
• The involvement of testicles, fallopian tubes or
ovaries may result in sterility.

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N. Gonorrhoeae….
• Rectal infections with N. gonorrhoeae occur in
about one-third of women with cervical infection.
• They most often result from autoinoculation with
cervical discharge and are rarely symptomatic.
• Ocular infections by N. gonorrhoeae can have
serious consequences of corneal scarring or
perforation.
• Ocular infections (ophthalmia neonatorum) occur
most commonly in newborns who are exposed to
infected secretions in the birth canal .
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N. meningitidis(meningococci)

• N. meningitidis posses capsules which is used for


serogroupings.
– There are12 serogroups (A, B, C, H, I, K, L,
W-135, X, Y,Z, 29E)
– Different serogroup responsible disease in
different areas
– Group A is common in Africa, Group C and A
are associated with epidemic disease
– Proteins and antigens in LOS used for
serotyping
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Haemophilus
• Pasteurellaceae has three genera
Haemophilus
 Actinobacillus
Pasteurella
Haemophilus (blood loving)
gram-ve, short rods, pleomorphic bacteria
Spcies
H. influnzae- more pathogenic
H. aegyptius- acute purulent conjunctivitis
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H. influnzae
• It is a free-living, humanadapted organism without another reservoir
• Its principal habitat is the nasopharynx, but it is found inhabiting
other mucosal surfaces including the genital tract and occasionally
the intestinal tract
some strains are capsulated
a. Serotypes a to f ( based on capsular antigens)
Hib is most virulent
b. biotypes I to VIII( biochemical)
 Encapsulated, Hib(biotype I) most pathogenic
 May present in small no. in URT of healthy people
 Cause meningitis , epiglottitis, cellulites (unvaccinated child)

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Chlamydiae
Definition and classification

• Small, obligate cell parasites with a Gram-negative cell wall.


• The reproductive cycle of the chlamydiae comprises two
developmental stages:
– The elementary bodies are optimally adapted to survival outside
of host cells.
– Reticulate bodies, are the form in which the chlamydiae
reproduce inside the host cells by means of transverse fission.

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Chlamydiae

• Three human pathogen species of chlamydiae are


known:
– C. psittaci
– C. trachomatis (with the biovars trachoma and
lymphogranulomavenereum), and
– C. pneumoniae.

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C. trachomatis

It is a pathogen that infects only humans

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Bordetella
• Extremely small aerobic gram negative cocco bacilli
• Contain seven species and 3 are associated with
human disease
• B. pertussis- whooping cough
• B. paraprtusis- Mild form of pertussis
• B. bronchiseptica- 10 disease of animal may cause
bronchopneumonia
• Species classification is based
1. Growth characteristic
2. Biochemical reaction
3. Antigenic properties

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B. pertussis
• Colonize respiratory epithelium
• Gram negative aerobic coccobacillus
• Oxidize only as not CHO
• Virulent factors
a. attachment proteins
1.Pertactin(P69) and filamentous hemagglutinis
Has receptors on membranes of ciliated respiratory
cells
Binds on CR3( glycoprotien receptor on macrophage)
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