Staphylococcus aureus
Gram-positive, catalase-positive, coagulase-positive coccus forming characteristic grape-like clusters. A ubiquitous anterior nares commensal (persistent carriage 20–30% of adults) and one of the most clinically dangerous pathogens. MRSA (methicillin-resistant) carries mecA on SCCmec encoding PBP2a — a low-affinity penicillin-binding protein that maintains transpeptidase activity when conventional PBPs are inhibited by all beta-lactams. Virulence is orchestrated by the Agr quorum-sensing system: low-density → adhesins (colonisation); high-density → secreted toxins (invasion). Key toxins include PVL (pore-forming leukocidin killing neutrophils), α-toxin (endothelial lysis), and superantigens TSST-1/SEs (activate up to 20% of all T cells → toxic shock syndrome). Bacteraemia carries 20–30% case fatality despite modern intensive care and antibiotics.
Classification & Structure
| Gram reaction | Gram-positive; thick peptidoglycan (~20–40 nm); pentaglycine cross-bridges (unique to S. aureus); TLR2/NOD2 PAMP; β-lactam target site (PBPs 1–4) |
| Morphology | Spherical cocci ~0.5–1.5 µm; divide in multiple planes forming grape-like clusters (staphyle = bunch); non-motile, non-spore-forming; facultative anaerobe; golden carotenoid pigment (staphyloxanthin) on nutrient agar |
| Cell wall | Peptidoglycan + wall teichoic acids (WTA: ribitol-phosphate; colonisation adhesin, TLR2 PAMP) + lipoteichoic acid (LTA) + Protein A (SpA: IgG Fc and Fab binding → anti-opsonisation) + polysaccharide capsule type 5/8 (↓C3b deposition) |
| Key virulence factors | PBP2a/mecA (MRSA resistance); Protein A (IgG anti-opsonisation); PVL/LukSF-PV (pore-forming leukocidin; CA-MRSA tissue necrosis); α-toxin/Hla (endothelial/keratinocyte lysis); TSST-1/SEs (superantigens → TSS); coagulase/vWbp (fibrin shield); SCIN/CHIPS/Sbi (complement + chemotaxis inhibition); PNAG/biofilm (catheter/implant colonisation); staphyloxanthin (ROS quenching) |
| Genome | ~2.8–2.9 Mb; GC ~33%; SCCmec (11 types) carries mecA at orfX; SaPI pathogenicity islands encode TSST-1 and SEs; Agr quorum-sensing (4 allelic groups, AIP pheromone-controlled); USA300 CA-MRSA clone carries SCCmec IV + PVL + ACME |
Pathogenesis
1 · Nasal carriage and skin colonisation
The anterior nares is the primary reservoir: WTA mediates binding to SREC-I and other nasal epithelial receptors; ClfB and IsdA bind loricrin and cytokeratin-10. Persistent carriers (30% of adults) carry higher bacterial loads and face greater risk of auto-inoculation to surgical sites and skin wounds. Nasal decolonisation with mupirocin ointment ± chlorhexidine body wash before elective surgery significantly reduces MRSA surgical site infections.
2 · Skin breach, adhesion, and abscess formation
Trauma, eczema, or surgical incisions expose subepithelial matrix proteins. MSCRAMMs (FnBPA/B, ClfA, CNA) tether S. aureus to fibronectin, fibrinogen, and collagen. At high bacterial density, Agr switches virulence from adhesins to secreted toxins: α-toxin lyses keratinocytes and endothelial cells; leukocidins kill infiltrating neutrophils. Coagulase converts fibrinogen → fibrin clot around the colony, creating the fibrin-walled abscess (furuncle/boil), which protects bacteria from phagocytosis.
3 · Bacteraemia and deep infection seeding
FnBPA/B binds fibronectin on activated endothelium; α-toxin disrupts endothelial tight junctions. S. aureus invades non-professional phagocytes (endothelial cells, osteoblasts) via FnBP–α5β1 integrin interaction, adopting a small colony variant (SCV) metabolically dormant phenotype evading antibiotics and immune surveillance. Bacteraemia seeds endocardium (tricuspid valve in IV drug users; prosthetic valves), bone/joints, vertebrae, kidneys, brain, and liver.
4 · Superantigen-driven toxic shock
TSST-1 and staphylococcal enterotoxins (SEB–SEIRU) bind outside the MHC-II peptide groove and crosslink to TCR Vβ chains, activating ALL T cells bearing that Vβ family (5–20% of the entire T-cell repertoire simultaneously). This generates a tsunami of IL-2, TNF-α, IFN-γ → fever, hypotension, multi-organ failure (TSS). Subsequent T-cell exhaustion and Treg expansion impair specific anti-staph adaptive responses for months. Scalded skin syndrome (SSSS) arises from epidermolytic toxins ETA/ETB cleaving desmoglein-1 → superficial skin blistering.
5 · MRSA mechanism: mecA and PBP2a
The mecA gene on SCCmec encodes PBP2a (PBP2′) — a low-affinity penicillin-binding protein that retains transpeptidase activity when conventional PBPs (1–4) are inhibited by all β-lactams including anti-staphylococcal penicillins and cephalosporins. VRSA (<20 cases ever) acquires vanA from VRE, adding glycopeptide resistance. Biofilm-associated infections require device removal plus rifampicin (biofilm-penetrating) combination therapy.
Host Immune Response
Disease Spectrum
| Disease | Key features | Mortality / outcome |
|---|---|---|
| Impetigo | Superficial skin; honey-crusted lesions; ETA/ETB cleave desmoglein-1 | Excellent; topical/oral antibiotics |
| Furuncle/carbuncle | Deep folliculitis/abscess; PVL strains in CA-MRSA; fluctuant | Excellent with incision and drainage ± oral antibiotics |
| Necrotising fasciitis type II | Rapidly spreading fascial necrosis; PVL + α-toxin; emergency debridement required | 30–70%; surgical emergency |
| Necrotising pneumonia | CA-MRSA (PVL+) post-influenza; haemoptysis; rapid respiratory failure | 60–75%; ICU, IV vancomycin + linezolid |
| Bacteraemia | Fever; positive blood cultures; 14-day minimum treatment; always evaluate for endocarditis | 20–30% |
| Infective endocarditis | Tricuspid (IVDU) or left-sided (prosthetic valve, healthcare); embolic phenomena; vegetation on echo | 20–40% (native valve); 45–60% (prosthetic valve) |
| Toxic shock syndrome (TSS) | Fever >38.9°C; hypotension; diffuse macular rash → desquamation; multi-organ dysfunction; TSST-1 (menstrual) or SE (non-menstrual) | 5–15%; IVIG neutralises toxins in severe cases |
| Scalded skin syndrome (SSSS) | ETA/ETB toxaemia → widespread superficial blistering; Nikolsky sign positive; neonates/immunocompromised | <5% children; 30–60% adults |
Treatment & Prophylaxis
| MSSA first-line | Anti-staphylococcal penicillins: flucloxacillin IV (UK/Europe) or nafcillin/dicloxacillin (US); OR cefazolin (equivalent efficacy, better tolerability for bacteraemia/endocarditis). Superior to vancomycin for MSSA bacteraemia. |
| MRSA first-line | Vancomycin (glycopeptide; inhibits transglycosylase/transpeptidase by binding D-Ala-D-Ala; AUC/MIC target ≥400–600 µg·h/mL); Daptomycin (cyclic lipopeptide; depolarises Gram-positive cell membrane; NOT for pneumonia — inhibited by surfactant); Linezolid (oxazolidinone; 50S ribosome inhibitor; excellent oral bioavailability). |
| Newer agents | Ceftaroline (5th-gen cephalosporin with MRSA activity; binds PBP2a); tedizolid; dalbavancin/oritavancin (long-acting lipoglycopeptides; single-dose for ABSSSI). |
| Biofilm/implant infections | Device removal is often necessary; rifampicin (biofilm-penetrating, always in combination) when device cannot be removed. Prolonged treatment courses required (6+ weeks for endovascular/osteoarticular infection). |
| Surgical site prophylaxis | Intranasal mupirocin ointment + chlorhexidine body wash for MRSA carriers before elective surgery; reduces SSI rates by ~60% in carriers. Cefazolin IV within 60 min of incision for MSSA prophylaxis; vancomycin for MRSA carriers. |
Cross-Atlas Connections
References
- Lowy FD. Staphylococcus aureus infections. N Engl J Med. 1998;339(8):520–32. doi:10.1056/NEJM199808203390806 · PubMed 9709046
- Gordon RJ, Lowy FD. Pathogenesis of methicillin-resistant Staphylococcus aureus infection. Clin Infect Dis. 2008;46 Suppl 5:S350–9. doi:10.1086/533591 · PubMed 18462090
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This entry covers S. aureus virulence mechanisms, MRSA resistance, and clinical management. Planned expansions: anti-virulence therapeutics (anti-α-toxin mAbs, anti-WTA phage endolysins), S. aureus vaccine pipeline, and host-directed therapy for persistent bacteraemia.