Staphylococci: Colonizers and Pathogens of Human Skin

Rosanna Coates; Josephine Moran; Malcolm J Horsburgh

Disclosures

Future Microbiol. 2014;9(1):75-91. 

In This Article

Sensing & Repelling Cationic AMPs

Although the human epidermis secretes an arsenal of AMPs to prevent infection, the colonizing and pathogenic bacteria have evolved countermeasures (Figure 2). The ApsSR sensing system of S. epidermidis is specific to cAMPs. The presence of a negatively charged extracellular loop domain in the ApsS sensor is required for selectivity and gene deletion mutants have reduced survival to hBD3.[60] The cAMP response induces resistance in S. epidermidis through regulation of the dlt and mprF operons.[60,61] The homologous APS system of S. aureus, GraRS, has a substitution of a serine for a proline residue in the extracellular loop, leading to altered expression of the dlt and mprF operons.[62] This potentially accounts for the different responses to AMPs by S. aureus and S. epidermidis.[62] Sensing and resistance of cAMPs through the GraRS system in S. aureus requires the contribution of GraX and the VraFG ABC transporter.[48,63–65]

Figure 2.

Proposed skin survival mechanisms of Staphylococcus aureus.
Selected factors of Staphylococcus aureus that are known or proposed to contribute to human skin survival.
+ve: Positive; AFA: Antimicrobial fatty acid; AMP: Antimicrobial peptide; CL: Cardiolipin; FAME: Fatty acid-modifying enzyme; PIA: Polysaccharide intercellular adhesion; PNAG: Poly N-acetyl glucosamine; WTA: Wall teichoic acid.

MprF modulates cell surface charge by the addition of lysine to the membrane lipid via lysyl-phosphatidylglycerol synthetase activity.[66,67] An mprF mutant of S. aureus has an increased susceptibility to killing by cAMPs,[68] owing to perturbation of the cell surface charge, which reduces its ability to repel the cAMPs.[69] Similarly, the dlt operon protects S. aureus from AMPs by modifying cell surface charge via covalent attachment of D-alanine to wall teichoic acids.[70] Mutations in dltA increase susceptibility to defensins and cathelicidins owing to the greater negative charge of the cell surface.[71]

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....