Topic 3: Gram-Positive Cocci — Staphylococcus & Streptococcus

Introduction

Gram-positive cocci are among the most clinically significant bacterial pathogens. Staphylococcus and Streptococcus species cause a wide spectrum of diseases ranging from minor skin infections to life-threatening sepsis, meningitis, and endocarditis. For FMGE, mastering the identification, pathogenicity, and laboratory diagnosis of these organisms is mandatory.

Staphylococcus

Classification and Key Species

The genus Staphylococcus contains over 40 species, but only a handful are clinically significant:

• Staphylococcus aureus — most pathogenic; coagulase-positive; causes pyogenic infections, food poisoning, toxic shock syndrome
• Staphylococcus epidermidis — coagulase-negative; normal skin flora; major cause of prosthetic device infections
• Staphylococcus saprophyticus — coagulase-negative; second most common cause of UTI in young sexually active women

Virulence Factors of S. aureus

S. aureus possesses an impressive array of virulence factors:

• Coagulase — converts fibrinogen to fibrin;的唯一 characteristic of S. aureus
• Protein A — binds Fc portion of IgG, preventing opsonization and phagocytosis
• Catalase — converts H₂O₂ to water and oxygen; protects against oxidative killing
• Beta-lactamase — degrades penicillin and ampicillin; widespread in clinical isolates
• Panton-Valentine leukocidin (PVL) — associated with necrotizing pneumonia and skin/soft tissue infections; community-associated MRSA often carries PVL
• Exfoliative toxins (ETA, ETB) — cause staphylococcal scalded skin syndrome (SSSS) and bullous impetigo
• Toxic Shock Syndrome Toxin-1 (TSST-1) — causes toxic shock syndrome (TSS) associated with superabsorbent tampon use and nasal packing
• Enterotoxins (A–E, G–J) — heat-stable toxins causing staphylococcal food poisoning (emetic form, incubation 1–6 hours)

Diseases Caused by S. aureus

Disease	Mechanism
Folliculitis, furuncles, carbuncles	Pyogenic skin infections
Acute bacterial endocarditis	IV drug users, prosthetic valves
Osteomyelitis	Often hematogenous in children
Pneumonia	Post-influenza, aspiration
Septic arthritis	Direct inoculation or hematogenous
Food poisoning	Preformed enterotoxin (emetic)
Toxic shock syndrome	TSST-1 superantigen
Scalded skin syndrome	Exfoliative toxins

Laboratory Diagnosis

• Gram stain: Gram-positive cocci in clusters
• Culture: Golden yellow (pigmented), beta-hemolytic colonies on blood agar
• Catalase test: Positive (distinguishes from Streptococcus)
• Coagulase test: Positive (definitive for S. aureus)
• Mannitol salt agar: Ferments mannitol (yellow); selective for Staphylococci
• DNase test: Positive — another identifying feature of S. aureus

MRSA (Methicillin-Resistant S. aureus)

MRSA possesses the mecA gene encoding PBP2a, which has low affinity for beta-lactam antibiotics. MRSA is resistant to all penicillins, cephalosporins, and carbapenems. Treatment options include vancomycin, linezolid, daptomycin, and clindamycin (if susceptible). HA-MRSA (hospital-associated) and CA-MRSA (community-associated) are epidemiologically distinct.

Streptococcus

Classification

Lancefield grouping (based on carbohydrate antigen on cell wall) is the classical classification system:

• Group A Streptococcus (GAS) — Streptococcus pyogenes — most pathogenic strep
• Group B Streptococcus (GBS) — Streptococcus agalactiae — neonatal meningitis, sepsis
• Group D — Streptococcus bovis — associated with colorectal cancer
• Viridans group — S. mutans, S. sanguinis — normal oral flora; cause subacute bacterial endocarditis
• Pneumococcus — Streptococcus pneumoniae — lancet-shaped diplococci

Streptococcus pyogenes (GAS)

Key characteristics:

• Beta-hemolytic (complete RBC lysis) on blood agar
• Bacitracin-sensitive (zone of inhibition around bacitracin disc) — used for presumptive identification
• PYR (pyrrolidonyl arylamidase) test positive

Diseases:

Category	Examples
Pyogenic	Pharyngitis, impetigo, cellulitis, erysipelas
Toxic	Scarlet fever (pharyngitis + rash + strawberry tongue)
Immunological	Rheumatic fever, post-streptococcal glomerulonephritis (PSGN)

Post-streptococcal sequelae (occurs 1–4 weeks after infection):

• Acute rheumatic fever (ARF) — follows pharyngitis; Jones criteria (major: carditis, polyarthritis, chorea, erythema marginatum, subcutaneous nodules; minor: fever, arthralgia, elevated ESR/CRP)
• PSGN — follows skin infection (impetigo) more than pharyngitis; results in hematuria, proteinuria, hypertension

Anti-streptolysin O (ASO) titer — elevated in ARF; Anti-DNase B — elevated in PSGN

Streptococcus pneumoniae

Morphology: Gram-positive, lancet-shaped diplococci (pointed ends); bile soluble; alpha-hemolytic on blood agar; optochin-sensitive

Diseases: Pneumonia (lobar, rust-colored sputum), meningitis, otitis media, sinusitis, bacteremia

Capsule: The polysaccharide capsule is the primary virulence factor. Quellung reaction (capsular swelling with specific antisera) is the gold standard for identification. The capsule is also the basis of pneumococcal vaccines (PCV13, PPSV23).

Laboratory Differentiation of Streptococci

Test	S. pyogenes	S. pneumoniae	S. viridans
Hemolysis	Beta	Alpha	Alpha
Bacitracin	Sensitive	Resistant	Resistant
Optochin	Resistant	Sensitive	Resistant
Bile solubility	Insoluble	Soluble	Insoluble
Bile esculin	Negative	Negative	Variable

FMGE High-Yield Points

• Coagulase-positive = S. aureus; coagulase-negative staphylococci = S. epidermidis, S. saprophyticus
• Food poisoning with short incubation (1–6 hours) = S. aureus enterotoxin (preformed toxin)
• Scarlet fever = GAS pharyngitis with rash and strawberry tongue
• Rheumatic fever follows pharyngitis; PSGN follows skin infection (impetigo)
• Strep pneumoniae = lancet-shaped diplococci, alpha-hemolytic, optochin-sensitive, bile-soluble
• Viridans streptococci = alpha-hemolytic, optochin-resistant, bile-insoluble; cause subacute endocarditis
• Group B Strep (S. agalactiae) = major cause of neonatal sepsis and meningitis; screened in pregnant women with rectal/vaginal swab

⚡ Exam tip: If USMLE/FMGE asks about a patient with a “sandpaper-like rash, strawberry tongue, and recent pharyngitis” — the answer is scarlet fever caused by Streptococcus pyogenes.