Lecture 4

Gram-positive cocci
Staphylococcus,. Streptococcus,

Eka Jaiani
EEU
2024
 INTRODUCTION
• Staphyloccocci - derived from Greek “stapyle”
(bunch of grapes)
• Gram positive cocci arranged in clusters
• Hardy organisms surviving many non
physiologic conditions
• Include a major human pathogen and skin
commensals
 Cell Morphology

• Spherical cells about

1µm in diameter
• Single cocci, pairs,
tetrads, clusters
•Young cultures
strongly gram positive
Cell Morphology
Staph vs. Strep
 Staphylococci
Staphylococcus aureus
• Major human pathogen

• Habitat - part of normal flora in some humans and

animals

• Source of organism - can be infected human host,

carrier, fomite or environment
 Staphylococcus aureus
Virulence Factors Antigenic structure

• Staphylococci contain antigenic

polysaccharides and proteins of the cell wall
• Capsule or slime layer (glycocalyx)
• Peptidoglycan (PG)- endotoxin like activity
 Staphylococcus aureus
Cell-Associated Virulence Factors- antigens
• Teichoic acid is covalently linked to PG and is
species specific:
– S. aureus ribitol teichoic acid
(polysaccharide A)
– S. epidermidis glycerol teichoic acid
(polysaccharide B)
– Can be antigenic ( antibodies found in patients)
• Protein A is covalently linked to PG
• Clumping factor (bound coagulase)
Protein A
 Virulence Factors
Extracellular Enzymes

• Coagulases (bound or free)

– Antigenic
• Hyaluronidase
– “spreading factor” of S. aureus
• Nuclease
– Cleaves DNA and RNA
• Protease
– Staphylokinase (fibrinolysin)
• Lipases
• Esterases
 Virulence Factors: Exotoxins
Cytolytic (cytotoxins, cytolysins)

•Alpha toxin - hemolysin • Delta toxin

Reacts with red blood cells ( RBCs) – Cytopathic for:
»RBCs
• Beta toxin »Macrophages
Sphingomyelinase - toxic for many »Lymphocytes
kind of cells, including RBSs »Neutrophils
»Platelets
• Gamma toxin Hemolytic – Enterotoxic activity
activity
three proteins
 Virulence Factors: Exotoxins

• Exfoliative toxin (epidermolytic toxins)

- two distinct proteins with same Mol.weight
- epidermolytic toxin A- chromosomal gene product ,
heat -stable
- epidermolytic toxin B- plasmid-mediated,
heat –labile
- dissolve mucopolysacharide matrix of epidermis
- cause staphylococcal scalded skin syndrome
- these toxins are superantigens
 Toxic shock syndrome toxin

• found in 20% of S. aureus isolates

• TSST-1 is the prototypical superantigen
- Yields T-cell stimulation
- Promotion of protein manifestation for toxic shock syndrome
( fever, shock, multisystem disoreders, skin rash)

Leukocidin
• Kill white blood cells ( human and rabbit)
• Panton- Valentine leukocidin interacts with γ-toxin and forms
six potential toxins
 Enterotoxins
• Mutiple Enterotoxins ( A-E, G-I, K-M)
• 50% od S.aureus strains produce one or more
enterotoxins
• Superantigens, heat stable , resistant to
action of gut enzymes
• Acts on neural receptors of the gut –
stimulates CNS( vomiting center)
• Food poisoning – when S. aureus grows in
carbohydrate and protein foods
 S.aureus
infections
 SKIN LESIONS
• Boils
• Furuncles (infection of hair follicle)
• Carbuncles (infection of several hair follicles)
• Wound infections (progressive appearance of
swelling and pain in a surgical wound after about
2 days from the surgery)
• Impetigo (skin lesion with blisters that break and
become covered with crusting exudate)
 Clinical Manifestations

• Toxin mediated infections

– Food poisoning vs. foodborne disease
– Toxic shock syndrome

• Systemic Infections
- Bacteremia
- Osteomyelitis
- Pulmonary and cardiovascular infection
 Staphylococcus epidermidis
• Skin commensal
• Has predilection for plastic material
• Ass. with infection of IV lines, prosthetic heart
valves, shunts
• Causes urinary tract infection in cathetarized
patients
• Has variable antibitotic sensititvity(ABS) pattern
• Treatment should be aided with ABS testing
 Stapylococcus saprophyticus

• Skin commensal
• Cause of UTI in sexually active young women
• Usually sensitive to wide range of antibiotics
 Treatment of Staph infections
• Serious skin infections occur mostly in adolescents or in patients
receiving prolonged course of corticostperiods
- Tetracyclins are used for long- term treatment
• Abscesses are treated by drainage and antimicrobial therapy (in vitro
testing)
• Hematogenous osteomyelitis
- Acute infection well responsive to antimicrobial therapy
- In chronic osteomyelitis eradication is difficult– drainage and
prolonged administration of proper drugs, also hyperbaric oxygen
• S. aureus Bacteriemia, endocarditis, pneumonia– severe diseases to
be treated with prolonged intravenous β lactamase –resistant
penicillin
-Vancomycin for nafcillin- resistant staphylococci
• S.epidermidis infections difficult to cure because of
- formation of biofilms ( on prosthetic devises)
- high resistance to antibiotics
• Newer durgs such linezolide, daptomycin are reserved for patients
with serious Staph and Strep infections who are failing clinically and/or
are highly allergic
 Streptococci
FAMILY Streptococcaceae

• Widely distributed in nature

• G+ spherical bacteria, form pairs and chains
• Some part of the normal flora, some- cause serious diseases
• Classification based on :
- colony morphology and hemolytic reactions;
- serologic specificity of cell wall substances
and /or capsular antigens
- biochemical properties
-ecologic features
- molecular genetics
 Streptococcus: Natural Habitats
• Streptococci are resident colonizers of mucous
membranes of
- mouth, nasopharyngeal cavity,
- gastrointestinal tract
- urogenital tract
• Streptococci are
transient colonizers
of the skin
 Enterococcus: Natural Habitats

• Enterococci can survive in harsh environments

(extremes of temperature, salinity, and pH)
• Ubiquitous in soil, water, plants, animals, birds, and
insects
• Enterococcus faecalis and E. faecium normally
inhabit the gastrointestinal and female genital tract
 Streptococci characterization - hemolysis

• Grouping streps by their ability to lyse RBCs

– Beta hemolysis( ): complete lysis of RBCs
– Alpha hemolysis ( ): resulting in an opaque
greenish-brown zone around colonies
– Gamma hemolysis ( ): no effect on RBCs
“gamma hemolysis” is synonymous to “no effect” -
“non-hemolytic streptococci”
Classification of Streptococci
Group specific substance ( Lancefeld)
Group A: -hemolytic Streptococcus pyogenes
Group B: -hemolytic (occasionally  or ) S. agalactiae
Group C, G: -hemolytic ( or ) S. dysgalactiae subspecies
equismilis
Group D:  or  hemolytic () Enterococci
Group F: -hemolytic S. anginosus
Viridans streptococci: (no group specific antigen)
 or  hemolytic S. mutans and
S. salivarius, S. sanguis, S. mitis and S. milleri groups
Streptococcus pneumoniae (no group antigen)(-hemolytic)

REVIEW
Group A Streps (GAS)
Streps of Clinical Significance
 Sore throat
• Streptococcal pharyngitis
Red swollen tonsils and pharynx
Purulent exudate on the tonsils
High temperature
Swollen lymph nodes.

Erysipelas
Infection of the superficial skin,
the dermis only. A raised, bright
red rash with a sharp border that
advances erysipelas from the site
of infection.
Erythema and celullitis
An acute spreading inflammation
of the skin and subcutaneous
tissues, usually results from
infection of burns, wounds, or
surgical incisions, but may also
follow mild trauma.
Bacteria attack the skin, the
tissue just beneath the skin
(subcutaneous tissue), tissues
are necrotized (Streptoccocal
gangrene ).
 Scarlet fever
• The first signs of scarlet fever
can be flu-like symptoms,
including a high temperature,
a sore throat and swollen neck
glands (a large lump on the
side of your neck).
• A rash appears 12 to 48 hours
later. It looks looks like small,
raised bumps and starts on
the chest and tummy, then
spreads. The rash makes your
skin feel rough, like
sandpaper. A white coating also appears on the tongue.
This peels, leaving the tongue red, swollen and
covered in little bumps (called "strawberry
tongue").
Delayed Antibody-Mediated Diseases
Rheumatic fever
• results in damage to heart muscle and valves.
• Joint swelling
• Rash
• Subcutaneous nodules
• Certain strains of group A streptococci contain
cell membrane antigens that
cross-react with human heart
tissue antigens.

Acute Glomerulonephritis
blood and protein in the urine, edema,
high blood pressure, and urea nitrogen
retention; chronic glomerulonephritis
with ultimate kidney failure; and the
majority recover completely.
S. agalactiae (GBS – Group B streptococci)
clinical Significance

– Neonatal meningitis / septicemia

– Cystitis and pyelonephritis
– Postpartum endometritis
– Postpartum septicemia
– Infections in women following caesarian section
– Pneumonia, endocarditis, arthritis, cellulitis in
adults.
 Streptococcus pneumoniae
Clinical Significance

– Community acquired typical bacterial

pneumonia
– Meningitis (any age group but predominates
in adults over 60)
– Sinusitis and otitis media
– Bacteremia and septicemia (usually
associated with meningitis and pneumonia)
 Enterococcus sp.
Clinical Significance
– Upper and lower urinary tract infections (mainly
nosocomial & nursing homes)
– Native valve and prosthetic valve endocarditis
– Intra-abdominal and pelvic infections
– Wound infections
– Septicemia and meningitis in neonates and rarely
other age groups
– Bacteremia third most common with ~2-9%
associated with endocarditis
 Clinical Significance
• Viridans streptococci

– A leading cause (#1 strep) of bacterial native valve

and prosthetic valve endocarditis
– Dental caries: capsule allows the bacterium (mainly
S. mutans & S. sobrinus) to adhere firmly to the
teeth. Adherent bacteria produce acid
fermentation products that dissolve the enamel of
the teeth
Streptococci treatment
Enterococci treatment
• Jawetz, Chapters 13, 14
• Levinson, Chapter 15