Staphylococcus aureus: Virulence, Toxins & Syndromes
How one skin colonizer makes abscesses, toxins, and resistant infections
The organism and its structural defenses
Identity. S. aureus is a gram-positive coccus that divides in several planes to form grape-like clusters. It is catalase-positive and coagulase-positive and grows as golden, β-hemolytic colonies; the carotenoid pigment staphyloxanthin also neutralizes oxidants and helps it survive the neutrophil oxidative burst. It tolerates high salt, so mannitol-salt agar (7.5% NaCl) selects for it, and mannitol fermentation turns the medium yellow. About 30% of people carry it in the anterior nares, and carriers are at higher risk after surgery, dialysis, or catheter placement.
Protein A. This cell-wall protein binds the Fc region of IgG, so antibodies attach in the wrong orientation. Opsonization, phagocytosis, and classical complement activation all fail.
Coagulase and clumping factor. Free coagulase activates prothrombin, converting fibrinogen to fibrin; cell-bound clumping factor binds fibrinogen directly. The resulting fibrin shield hides the bacteria from phagocytes and forms the wall of the abscess, the organism's signature lesion.
Microcapsule and biofilm. A thin polysaccharide microcapsule resists phagocytosis, and biofilm on catheters, prosthetic joints, and heart valves protects bacteria from antibiotics and host defenses. Patients with chronic granulomatous disease, whose neutrophils cannot kill catalase-positive organisms, suffer recurrent staphylococcal abscesses.
Toxins
| Toxin | Mechanism | Disease |
|---|---|---|
| TSST-1 | Superantigen: links MHC II and TCR Vβ outside the peptide groove → polyclonal T-cell activation | Toxic shock syndrome |
| Exfoliative toxins A and B | Serine proteases that cleave desmoglein-1 in the granular layer | Scalded skin syndrome; bullous impetigo (localized form) |
| Enterotoxins | Heat-stable, preformed superantigens that trigger vomiting | Food poisoning |
| Panton-Valentine leukocidin | Pore-forming toxin that kills neutrophils and macrophages | Recurrent furuncles, necrotizing pneumonia (community MRSA) |
| α-Toxin | Pore-forming toxin lysing RBCs, platelets, leukocytes, epithelial and endothelial cells | Tissue necrosis; β-hemolysis; severity of pneumonia and skin infection |
Superantigens. Ordinary antigens are processed and displayed in the MHC class II groove, activating the few T cells specific for them. TSST-1 and the enterotoxins instead bridge MHC class II and the Vβ region of the T-cell receptor from the outside, activating a large fraction of all T cells at once. The resulting flood of IL-1, IL-2, TNF-α, and IFN-γ causes fever, capillary leak, and shock.
Toxin-mediated syndromes
Toxic shock syndrome. Toxin is produced at a colonized, often closed site: a retained tampon, nasal packing, a surgical or postpartum wound. Features are high fever, diffuse macular sunburn-like erythroderma, hypotension, and involvement of three or more organ systems (vomiting and diarrhea, myalgias with high CK, mucosal hyperemia, renal and hepatic injury, thrombocytopenia, confusion). Palms and soles desquamate 1–2 weeks later. Blood cultures are usually negative because disease reflects toxin absorbed from a local site; streptococcal TSS, by contrast, usually has positive blood cultures and a painful soft-tissue focus.
In toxic shock, remove the source (tampon, packing, infected wound) and add clindamycin to an antistaphylococcal agent, because clindamycin suppresses toxin synthesis at the ribosome.
Staphylococcal scalded skin syndrome. Exfoliative toxin from a localized infection circulates and cleaves desmoglein-1, splitting the epidermis high in the granular layer. It affects neonates and young children, who clear the toxin poorly and lack antitoxin antibodies, and occasionally adults with kidney failure. Fever and tender erythema are followed by flaccid bullae and sheet-like peeling with a positive Nikolsky sign. Mucous membranes, which rely on desmoglein-3, are spared, and the skin heals without scarring. Bullous impetigo is the localized form of the same toxin effect.
| Feature | Scalded skin syndrome | Toxic epidermal necrolysis |
|---|---|---|
| Cause | S. aureus exfoliative toxin | Drug reaction (sulfonamides, anticonvulsants, allopurinol) |
| Patients | Neonates, young children | Mostly adults |
| Level of split | Granular layer (desmoglein-1) | Full-thickness epidermal necrosis at the dermal-epidermal junction |
| Mucosa | Spared | Involved |
| Outcome | Heals without scarring | High mortality; scarring possible |
Food poisoning. Food handlers contaminate custards, cream pastries, mayonnaise-based potato or egg salads, and ham, and the organism multiplies and releases enterotoxin when the food sits at room temperature. The toxin is preformed and heat-stable, so reheating kills the bacteria but not the toxin. Nausea, vomiting, and cramps begin abruptly 1–6 hours after the meal, usually without fever, and resolve within about a day. Bacillus cereus emetic toxin in reheated fried rice causes a similar rapid-onset illness.
Invasive and suppurative syndromes
- Skin and soft tissue: bullous and nonbullous impetigo, folliculitis, furuncles, carbuncles, abscesses, and purulent cellulitis. Incision and drainage is the key treatment for an abscess; antibiotics are added for large or multiple lesions, systemic signs, or immunocompromise.
- Endocarditis: S. aureus is the leading cause of infective endocarditis and follows an acute, destructive course even on normal valves. In people who inject drugs it favors the tricuspid valve (murmur louder on inspiration) and throws septic pulmonary emboli, seen as multiple peripheral cavitary nodules.
- Bone and joint: the most common cause of osteomyelitis (metaphyseal hematogenous disease in children, vertebral osteomyelitis in adults, contiguous spread from diabetic foot ulcers) and of septic arthritis in adults, except that N. gonorrhoeae predominates in young, sexually active adults. Salmonella is a classic association in sickle cell disease and Pseudomonas after a nail puncture through a shoe.
- Pneumonia: cavitating, necrotizing pneumonia after influenza, ventilator-associated pneumonia, empyema, and pneumatoceles in children.
- Bacteremia: often from intravascular catheters, with seeding of bones, joints, and heart valves.
Panton-Valentine leukocidin. Community-acquired MRSA strains usually carry PVL, which kills neutrophils and macrophages. They cause recurrent furuncles and abscesses, spreading in households, sports teams (for example, wrestlers), prisons, and the military, and a necrotizing, hemorrhagic pneumonia after influenza in previously healthy young people.
S. aureus in a blood culture is never dismissed as a contaminant: remove infected lines, repeat cultures until negative, and obtain an echocardiogram to look for endocarditis.
MRSA: resistance and treatment
Mechanism. Most S. aureus strains make penicillinase, so penicillin G is rarely useful. Methicillin resistance is different: the mecA gene, carried on the mobile staphylococcal cassette chromosome mec (SCCmec), encodes PBP2a, a transpeptidase with low affinity for β-lactams that keeps building cell wall when the native PBPs are blocked. MRSA is therefore resistant to penicillinase-resistant penicillins, most cephalosporins, and carbapenems; ceftaroline is the β-lactam designed to bind PBP2a.
| Drug | Main use | Key caveat |
|---|---|---|
| Nafcillin, oxacillin, cefazolin | Methicillin-susceptible S. aureus | Better than vancomycin for MSSA; inactive against MRSA |
| Vancomycin | Serious MRSA infection | Nephrotoxicity; infusion-related flushing |
| Daptomycin | MRSA bacteremia and endocarditis | Inactivated by surfactant, so not for pneumonia; CK elevation, myopathy |
| Linezolid | MRSA pneumonia, skin infection; oral option | Thrombocytopenia; serotonin syndrome with SSRIs |
| Ceftaroline | MRSA skin infection and pneumonia | Only β-lactam class active against PBP2a |
| TMP-SMX, doxycycline, clindamycin | Oral therapy of MRSA skin infection | Clindamycin can have inducible resistance |
Decolonization. Intranasal mupirocin, often with chlorhexidine washes, reduces carriage in patients with recurrent infection or before certain surgeries.
Coagulase-negative staphylococci
S. epidermidis. This novobiocin-sensitive skin commensal produces a biofilm of extracellular polysaccharide that lets it colonize catheters, prosthetic joints and heart valves, pacemakers, and CSF shunts, causing indolent device infections. It is the most frequent blood culture contaminant: one positive bottle among several sets suggests contamination, whereas repeated positive sets in a patient with a device suggest true infection. Many strains are methicillin-resistant, so vancomycin plus removal of the device is typical.
S. saprophyticus. This novobiocin-resistant organism colonizes the genitourinary tract, adheres to uroepithelium, and is second only to E. coli as a cause of uncomplicated cystitis in sexually active young women.