Virulence factor and Infections Caused by Staphylococcus aureus

Staphylococcus aureus

Introduction	Staphylococcus aureus is Gram-positive,non-motile, coagulase-positive bacterium arranged in grape-like clusters. According to CDC, about 30% of the people carry them in their nose. Although being a commensal, it also causes a health-care-associated infection.
Strains associated with different infections	The Staphylococcus genus includes 52 species and 28 subspecies (List of Prokaryotic names with Standing in Nomenclature) and is most common isolate in clinical specimen. Strains of Staphylococcus aureus associated with different infections include: 1. Methicillin-resistant Staphylococcus aureus (MRSA) 2. Methicillin-susceptible Staphylococcus aureus (MSSA) 3. Vancomycin-intermediate Staphylococcus aureus (VISA) 4. Vancomycin-resistant Staphylococcus aureus (VRSA)
1. Methicillin-resistant Staphylococcus aureus (MRSA)	Methicillin-resistant Staphylococcus aureus (MRSA) is resistant to certain antibiotics called beta-lactams (methicillin and other antibiotics such as oxacillin, penicillin and amoxicillin). MRSA was first emerged in England during 1960s. It has now become a leading cause of bacterial infection in both health-care and community settings. Most of the infections caused by MRSA are skin infections that often appear as a bump, a boil, or area that is red, tender and swollen. Most severe infections occur most frequently among patients in health care settings. The spread of MRSA occurs by two mechanisms: i) spread of existing resistant clones ii) acquisition of staphylococcal cassette chromosome mec (SCCmec) by a methicillin-sensitive S. aureus (MSSA) The mecA gene encodes penicillin-binding protein 2a (PBP2a) responsible for crosslinking the peptidoglycan in the bacterial cell wall. There are limited reports on details of mechanism of horizontal transfer of SCCmec. However, epidemiological evidence elucidated that this resistance mechanism has spread to most clones of pathogenic strains of S. aureus associated in both human and animal [2,3]. Although there are limited therapeutic option for MRSA but several new antibiotics are under development [4].
2. Methicillin-susceptible Staphylococcus aureus (MSSA):	Methicillin-resistant Staphylococcus aureus (MRSA) is suceptible to beta-lactam antibiotics.
3. Vancomycin-intermediate Staphylococcus aureus (VISA)	Staphylococcus are classified as VISA if the MIC for vancomycin is 4-8 µg/mL.
4. Vancomycin-resistant Staphylococcus aureus (VRSA)	Staphylococcus are classified as VRSA if the MIC is ≥16 µg/mL.
Virulence factors of Staphylococcus aureus are listed below [4]	Type of Virulence Factors 1. Microorganism-associated molecular pattern (MAMPs) A. Chemotactic MAMPs *Formylated peptides *Phenol-soluble modulins (PSMs) B. Non-chemotactic MAMPs *Lipoproteins *DNA *Peptidoglycan 2. Adhesins A. Surface Proteins *Fibronectin-binding protein A (FnBPA) and FnBPB *Collagen adhesin (Cna) *Iron-regulated surface determinant protein A (IsdA) B. Glycopolymers *Wall teichoic acid (WTA) 3. Evasins A. MAMP receptor inhibitors *Chemotaxis inhibitory protein of S. aureus (CHIPS) *FPR-like 1 (FPRL1) inhibitory protein (FLIPr) *FLIPr-like Staphylococcal superantigen-like protein 3 (SSL3) *SSL5 B. Chemokine receptor inhibitors *SSL5 *SSL10 C. PMN extravasation inhibitors *SSL5 *Extracellular adherence protein (Eap) D. Coagulation factors *Coagulase (Coa) *Secreted von Willebrand factor binding protein (vWbp) *Clumping factor A (ClfA) *ClfB E. Anticoagulants *Staphylokinase F. Complement inhibitors *Zinc metalloproteinase aureolysin *Staphylococcal complement inhibitor (SCIN) *Fibrinogen-binding protein (Efb) *Extracellular complement-binding protein (Ecb, also known as extracellular fibrinogen-binding protein) *SSL7 *Immunoglobulin-binding protein Sbi G. Opsonophagocytosis inhibitors *Staphylococcus protein A (SpA) *Immunoglobulin-binding protein Sbi *Microcapsule *FLIPrb H. Synthases of anti-phagocytic mediators *Adenosine synthase (AdsA) I. Inhibitors of PMN killing *Catalase *Superoxide dismutase [Mn] 1 (SodA) *Staphyloxanthin *Eap *Staphylococcal peroxidase inhibitor (SPIN) *O‑Acetyltransferase A (OatA) *Multiple peptide resistance factor (MprF) *D‑alanine transfer protein A (DltA), DltB, DltC and DltD *Thermonuclease (Nuc) 4. Toxins A. Pore-forming protein toxins *α‑Toxin *Bi-component γ‑Haemolysin (Hlg) AB *Bi-component HlgCB *Leukocidin (Luc) ED *LucAB *Panton–Valentine leukocidin (PVL) B. Pore-forming peptide toxins *PSMα1–PSMα4 *PSMβ1 and PSMβ2 *SCCmec-encoded PSM (PSMmec *δ‑Toxin (also known as δ‑haemolysin, Hld) C. Superantigen toxins *Toxic shock syndrome toxin 1 (TSST1) *Enterotoxins types (SE) A‑Q *Staphylococcal enterotoxin-like X (SEIX) D. Sphingomyelinase *β‑Haemolysin (Hlb) *E. Proteolytic toxins *Exfoliative toxins (Etx)

Infections caused by Staphylococcus aureus

1. Bacteraemia and endocarditis

2. Pneumonia

3. Osteomyelitis: Osteomyelitis is an infection of bone. It resutls in inflammatory destruction of bones, bone necrosis, and new bone formation.The Waldvogel classification system [5] describes three types of OM: hematogenous OM, contiguous-focus OM, and OM with vascular insufficiency. Hematogenous OM generally involves the ends of long bones in children and adolescents and the axial skeleton in older adults [6], partly due to the blood supply to vertebrae in adults being more extensive than that to the long bones. Contiguous-focus OM originates from adjacent structures such as joint spaces or soft tissues or from trauma or surgery with direct implantation of organisms. OM with vascular insufficiency most commonly affects patients with diabetes or peripheral vascular disease and generally involving the foot.

4. Prosthetic joint infection

5. Skin and soft tissue infection (SSTIs) : S. aureus causes a variety of SSTIs, ranging from the benign to life-threatening. The benign forms are impetigo and uncomplicated cellulitis. It is the most common pathogen isolated from surgical site infections (SSIs), cutaneous abscesses, and purulent cellulitis.[7]

6. OTHER STAPHYLOCOCCAL CLINICAL SYNDROMES Epidural Abscess Meningitis Toxic Shock Syndrome Urinary Tract Infection

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References

1. Jevons, M. “Celbenin”-resistant staphylococci. BMJ 1, 124–125 (1961).

2. Enright, M. C., Day, N. P., Davies, C. E., Peacock, S. J. & Spratt, B. G. Multilocus sequence typing for characterization of methicillin-resistant and methicillin-susceptible clones of Staphylococcus aureus. J. Clin. Microbiol. 38, 1008–1015 (2000).

3. Monecke, S. et al. A field guide to pandemic, epidemic and sporadic clones of methicillin-resistant Staphylococcus aureus. PLoS ONE 6, e17936 (2011).

4. Lee, A., de Lencastre, H., Garau, J. et al. Methicillin-resistant Staphylococcus aureus. Nat Rev Dis Primers 4, 18033 (2018). https://doi.org/10.1038/nrdp.2018.33

5. Waldvogel FA, Medoff G, Swartz MN. 1970. Osteomyelitis: a review of clinical features, therapeutic considerations and unusual aspects. N Engl J Med 282:198–206. http://dx.doi.org/10.1056/NEJM197001222820406.

6. Espersen F, Frimodt-Moller N, Skinhoj P, Bentzon MW. 1991. Changing pattern of bone and joint infections due to Staphylococcus aureus: study of cases of bacteremia in Denmark, 1959-1988. Rev Infect Dis 13: 945–948.

7. http://cmr.asm.org