Staphylococci: Colonizers and Pathogens of Human Skin

Rosanna Coates; Josephine Moran; Malcolm J Horsburgh


Future Microbiol. 2014;9(1):75-91. 

In This Article

AFA Defense

Wall teichoic acids and the MSCRAMM IsdA contribute to AFA resistance of S. aureus by reducing hydrophobicity to limit AFA interaction (Figure 2).[102,104,105] The reduction of cell surface hydrophobicity is a response to AFAs.[106] Challenge with AFAs increased transcription of capsule and peptidoglycan genes,[106] which might contribute to the reduced hydrophobicity in response to AFAs. In addition to IsdA, the homologous MSCRAMMs SasF and SssF contribute to protection from AFAs.[106,107] In S. aureus, SasF transcription was upregulated 30-fold following exposure to linoleic acid (18:2Δ9,Δ12) and a replacement mutant had reduced AFA survival.[106] SssF complemented a S. aureus sssF mutant and clinical isolates of S. saprophyticus bearing SssF were more resistant to linoleic acid (18:2Δ9,Δ12) compared with those without SssF.[107] No discrete enzyme activity has yet been reported for these proteins.

S. aureus biosynthesis of the carotenoid staphyloxanthin aids survival from AFA-generated membrane disorder.[108] Staphyloxanthin also contributes to antioxidant defense and counteracts AMP-mediated membrane fluidity.[109,110] The inactivation of crtM decreases S. aureus survival from AFAs and transcriptomic studies revealed upregulated crtM transcription after linoleic acid (18:2Δ9,Δ12) exposure.[106]

The exoprotein fatty acid-modifying enzyme (FAME) is produced by S. aureus and S. epidermidis and esterifies lipids with cholesterol or primary alcohols to reduce their cellular toxicity.[111,112] Of 51 S. epidermidis isolates tested, the majority (88.2%) expressed FAME activity, demonstrating that FAME is widespread but potentially inessential for skin survival.[111] FAME activity is inhibited by triglycerides and diglycerides, which may explain why most staphylococci isolated from skin have lipase activity.[112] Lipases hydrolyze triglycerides and diglycerides releasing free fatty acids as substrates for FAME. Lipase and FAME are expressed by other staphylococcal species, being found particularly frequently in strains of S. aureus, S. saprophyticus, S. schleiferi and S. cohnii, but less often in strains of S. warneri, S. epidermidis, S. caprae, S. hominis, S. simulans and S. capitis. Neither activity was present in assays of S. lugdunensis or S. haemolyticus.[113] Notably, FAME was found frequently in S. simulans strains in the absence of lipase activity,[113] which might indicate community interactions.

FAME could represent just one of several staphylococcal enzymes to detoxify AFAs. Campbell et al. observed S. aureus activity for the saturation of linoleic acid (18:2Δ9,Δ12) into the less-toxic oleic and stearic acids; other strains converted linoleic acid (18:2Δ9,Δ12) to mysteric and steric acids.[114] Recent studies identified that the myosin cross-reactive antigen protein of S. pyogenes is a fatty acid hydratase and a myosin cross-reactive antigen homolog is encoded by S. aureus.[115] Additional factors reported to contribute to AFA survival include the arginine deiminase pathway, VraE permease, and an Mmpl-like transporter (SAR2632) (Figure 2);[106] however, the contributing mechanisms increasing survival have not been investigated.