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Foundational Sciences · Microbiology

Gram-Positive Cocci: Staph & Strep

A high-yield STEP 1 microbiology lesson on Gram-positive cocci that walks the boards' lab algorithm (morphology → catalase → coagulase/hemolysis → confirmatory tests) and maps each Staphylococcus and Streptococcus species to its virulence factors, classic vignette buzzwords, diseases, and treatment. Includes a full comparison table, vignette drills, a toxin deep-dive, post-strep sequelae, and only genuine, standard mnemonics (no fabricated acronyms).

15 min readHigh yield

The Big Picture: Running the Gram-Positive Coccus Algorithm

Every organism in this lesson is a Gram-positive coccus — a purple sphere on Gram stain. The boards rarely just hand you the name; they hand you lab clues and expect you to run the branching algorithm:

  1. Morphology on Gram stain. Grape-like clusters → Staphylococcus. Chains or pairs (diplococci) → Streptococcus / Enterococcus.
  2. Catalase test (add H₂O₂). Bubbles = catalase positive = *Staphylococcus. No bubbles = catalase negative = Streptococcus/Enterococcus*.
  3. For Staph, do the coagulase test. Coagulase positive = *S. aureus (converts fibrinogen → fibrin, forming a clot). Coagulase negative = S. epidermidis vs S. saprophyticus*, split by novobiocin.
  4. For Strep, read the hemolysis on blood agar. β-hemolysis (complete, clear zone), α-hemolysis (partial, green), or γ (none) — then confirm with optochin, bacitracin, bile-esculin, CAMP, and PYR tests.

Learn the algorithm and most "unknown organism" vignettes solve themselves before you even reach the disease.

Staphylococcus (Catalase Positive) — Must Knows
  • All staph are catalase positive — this is the single feature that separates them from strep.
  • S. aureus: catalase +, coagulase +, β-hemolytic, golden/yellow colonies, ferments mannitol (yellow on mannitol salt agar).
  • Protein A is S. aureus's key virulence factor: binds the Fc region of IgG, blocking opsonization and complement fixation.
  • S. aureus diseases: skin/soft-tissue infections & abscesses, acute bacterial endocarditis (tricuspid valve in IV drug users), osteomyelitis (most common cause overall), septic arthritis, post-influenza pneumonia (patchy/bronchopneumonia pattern, can cavitate), toxic shock syndrome (TSST-1), scalded skin syndrome, and rapid-onset food poisoning (preformed enterotoxin).
  • MRSA resistance = mecA gene → altered penicillin-binding protein PBP2a → resistant to all β-lactams except the anti-MRSA cephalosporin ceftaroline.
  • Coagulase-negative staph split by novobiocin: S. epidermidis is novobiocin *sensitive* → biofilms on prosthetic devices, catheters, and prosthetic valves (common blood-culture contaminant). S. saprophyticus is novobiocin *resistant* → UTI in young, sexually active women (2nd most common cause after E. coli).
  • Treatment: MSSA → nafcillin / oxacillin / dicloxacillin or cefazolin. MRSA → vancomycin (alternatives: linezolid, daptomycin, ceftaroline); community-MRSA SSTI → TMP-SMX, doxycycline, or clindamycin.
Gram stain of Staphylococcus aureus showing gram-positive cocci arranged in grape-like clusters
Staphylococcus aureus on Gram stain: gram-positive cocci in grape-like clusters — the morphology that flags Staphylococcus before the catalase test. · Wikimedia Commons — Y Tambe — CC BY-SA 3.0, via Wikimedia Commons
Streptococcus & Enterococcus (Catalase Negative) — Must Knows
  • All strep are catalase negative. Subgroup them by hemolysis, then confirm with a specific test.
  • α-hemolytic (green):
  • *S. pneumoniae* — optochin sensitive, bile *soluble*, lancet-shaped diplococci, encapsulated (positive Quellung reaction), IgA protease. #1 cause of the MOPS diseases. Rusty sputum, lobar pneumonia.
  • Viridans group (S. mutans, S. sanguinis, S. mitis) — optochin resistant, bile *insoluble*, no capsule. S. mutans → dental caries; S. sanguinis → subacute endocarditis on previously damaged valves (dextran-mediated adherence after dental work).
  • β-hemolytic (clear):
  • Group A — *S. pyogenes* — bacitracin sensitive, PYR +. M protein, streptolysin O (→ ASO titers), pyrogenic exotoxins.
  • Group B — *S. agalactiae* — bacitracin resistant, CAMP test +, hippurate +. Colonizes the vagina → neonatal meningitis, pneumonia, sepsis; screen mothers at 35–37 weeks and give intrapartum penicillin/ampicillin.
  • Group D:
  • Enterococcus (E. faecalis / faecium) — bile-esculin + and grows in 6.5% NaCl; PYR +. UTI, biliary infection, subacute endocarditis after GI/GU procedures. VRE → linezolid or daptomycin.
  • S. gallolyticus (bovis) — bile-esculin + but does NOT grow in 6.5% NaCl. Bacteremia/endocarditis → work up for colon cancer (colonoscopy).
Photomicrograph of Streptococcus pyogenes bacteria arranged in chains
Streptococcus pyogenes (Group A strep) in chains — the classic strep morphology; catalase negative, bacitracin sensitive, PYR positive. · Wikimedia Commons — Photo Credit: Content Providers(s): — Public domain, via Wikimedia Commons

Comparison Table: Organism → Key Feature → Disease → Treatment

OrganismKey lab featureClassic diseaseTreatment
S. aureusCatalase +, coagulase +, β-hemolytic, mannitol +; protein ASSTI/abscess, acute endocarditis (IVDU, tricuspid), osteomyelitis, TSS, scalded skin, food poisoningMSSA: nafcillin/cefazolin; MRSA: vancomycin
S. epidermidisCatalase +, coagulase −, novobiocin sensitive; biofilmProsthetic device/catheter & prosthetic-valve infectionVancomycin + remove device
S. saprophyticusCatalase +, coagulase −, novobiocin resistantUTI in young sexually active women (2nd most common)Nitrofurantoin or TMP-SMX
S. pneumoniaeα-hemolytic, optochin sensitive, bile soluble, encapsulated lancet diplococciLobar pneumonia (rusty sputum), adult meningitis, otitis media, MOPSAmoxicillin/penicillin; meningitis: ceftriaxone + vancomycin
Viridans strepα-hemolytic, optochin resistant, bile insolubleDental caries (mutans); subacute endocarditis on damaged valve (sanguinis)Penicillin (± gentamicin)
S. pyogenes (GAS)β-hemolytic, bacitracin sensitive, PYR +Pharyngitis, impetigo, erysipelas, necrotizing fasciitis, scarlet fever, TSS; sequelae RF & PSGNPenicillin
S. agalactiae (GBS)β-hemolytic, bacitracin resistant, CAMP +, hippurate +Neonatal sepsis, meningitis, pneumoniaAmpicillin/penicillin; intrapartum prophylaxis
EnterococcusCatalase −, bile-esculin +, grows in 6.5% NaCl, PYR +UTI, biliary infection, subacute endocarditis (post-GI/GU)Ampicillin; VRE: linezolid/daptomycin
S. gallolyticus (bovis)Bile-esculin +, no growth in 6.5% NaClBacteremia/endocarditis → colon cancerPenicillin + colonoscopy workup
Vignette Buzzwords → Organism → Treatment
  • "Menstruating woman with a tampon (or post-op nasal packing): fever, diffuse macular rash, hypotension, then desquamation of palms/soles." → S. aureus toxic shock syndrome (TSST-1 superantigen). → Remove source, fluids/pressors, clindamycin + vancomycin.
  • "IV drug user, fever, new tricuspid regurgitation murmur, septic pulmonary emboli." → S. aureus acute endocarditis. → Nafcillin (MSSA) or vancomycin (MRSA).
  • "2–6 hours after a picnic (potato salad/mayonnaise, custard): sudden vomiting, no fever, resolves in a day." → S. aureus food poisoning (heat-stable preformed enterotoxin). → Supportive only.
  • "Rusty-colored sputum, lobar consolidation, Gram-positive lancet-shaped diplococci." → S. pneumoniae pneumonia. → Amoxicillin/ceftriaxone.
  • "Man 2 weeks after a dental cleaning: low-grade fever, splinter hemorrhages, vegetation on a previously damaged mitral valve." → Viridans (S. sanguinis) subacute endocarditis. → Penicillin + gentamicin.
  • "Rapidly spreading, exquisitely painful skin infection with pain out of proportion to exam, dusky skin/hemorrhagic bullae, tissue necrosis, and systemic toxicity." → S. pyogenes (Group A strep) necrotizing fasciitis ("flesh-eating"). → Emergent surgical debridement + penicillin + clindamycin (clindamycin suppresses toxin production).
  • "Sandpaper rash, strawberry tongue, circumoral pallor after a sore throat." → Scarlet fever (S. pyogenes, erythrogenic/pyrogenic exotoxin). → Penicillin.
  • "5-day-old neonate: fever, lethargy, bulging fontanelle; mother had no prenatal screening." → Group B strep (S. agalactiae) meningitis. → Ampicillin.
  • "Elderly man with Streptococcus gallolyticus/bovis bacteremia or endocarditis." → Colonoscopy — screen for colon cancer.
Virulence Factors & Toxins the Boards Love
  • Superantigens (TSST-1 of S. aureus and SPE-A of S. pyogenes): bridge MHC II to the T-cell receptor outside the antigen groove → nonspecific, polyclonal T-cell activation → massive IL-1, IL-2, IFN-γ, TNF-α release → toxic shock.
  • Protein A (S. aureus): binds Fc of IgG → antiphagocytic (blocks opsonization/complement).
  • Exfoliative toxins (S. aureus): proteases that cleave desmoglein-1 → scalded skin syndrome / bullous impetigo (positive Nikolsky sign).
  • Staph enterotoxin: heat-stable, preformed → rapid-onset food poisoning (also a superantigen).
  • M protein (S. pyogenes): antiphagocytic; shares epitopes with myocardium → molecular mimicry → rheumatic fever.
  • Streptolysin O: oxygen-labile, antigenic hemolysin → anti-streptolysin O (ASO) titers rise (evidence of recent GAS infection). Streptolysin S is oxygen-stable and non-antigenic.
  • Streptokinase: activates plasminogen → plasmin → dissolves clots. Also hyaluronidase, DNase B, C5a peptidase.
  • S. pneumoniae: the polysaccharide capsule is the main virulence factor (antiphagocytic) — hence severe disease in asplenic / sickle-cell patients; plus IgA protease and pneumolysin.
Scanning electron micrograph of vancomycin-intermediate Staphylococcus aureus (VISA) with thickened cell walls
Vancomycin-intermediate S. aureus (VISA) by scanning EM — a reminder that S. aureus resistance drives the MSSA (nafcillin) vs MRSA (vancomycin) treatment split. · Wikimedia Commons — Content Providers(s): CDC/ Matthew J. Arduino, DRPH Photo Credit: Janice Haney Carr — Public domain, via Wikimedia Commons

Non-Suppurative Sequelae of Group A Strep: RF vs PSGN

Two immune-mediated complications follow S. pyogenes — distinguish them because the boards test the differences hard.

Acute rheumatic fever (ARF) follows pharyngitis only and is a type II hypersensitivity (antibody/molecular mimicry against M protein cross-reacting with heart tissue). Diagnose with the JONES criteria. Late complication: mitral stenosis. Prevented by promptly treating strep throat with penicillin.

Post-streptococcal glomerulonephritis (PSGN) follows either pharyngitis OR skin infection (impetigo) and is a type III (immune-complex) disease. Classic vignette: a child ~2 weeks after infection with cola-colored (hematuric) urine, periorbital edema, hypertension, and low serum C3. On EM: subepithelial "humps"; on IF: granular ("lumpy-bumpy") IgG/C3 deposits. Usually self-limited in children — and, unlike ARF, antibiotic treatment does NOT prevent it.

The Real Micro Classics (Only Genuine Ones)
  • Optochin — "O-p-tochin": the p reminds you Pneumococcus is optochin-sensitive (and bile-soluble); viridans strep are optochin-resistant (and bile-insoluble). This one split separates the two α-hemolytic groups.
  • MOPS — the top S. pneumoniae diseases: Meningitis, Otitis media (children), Pneumonia, Sinusitis.
  • JONES (♥) — major criteria for rheumatic fever: Joints (migratory polyarthritis), the O is a heart = carditis, subcutaneous Nodules, Erythema marginatum, Sydenham chorea.
  • Sensitivity directions worth memorizing straight (no gimmick needed): Group A strep = bacitracin sensitive, PYR +; Group B = bacitracin resistant, CAMP + / hippurate +. S. epidermidis = novobiocin sensitive; S. saprophyticus = novobiocin resistant.
  • Bile-esculin positive and growth in 6.5% NaCl = *Enterococcus; S. gallolyticus (bovis*) is bile-esculin positive but fails the salt test — the one-line way to separate the two group-D bugs.

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