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

AMPs Protect the Mammalian Epidermis

In concert with gaining a foothold on the epidermis, staphylococci are challenged to maintain colonization in the face of antimicrobial defense mechanisms. The cationic and anionic AMPs, together with lysozyme and RNases (see section below) form part of the host's first line of defense, the innate immune system.

Epithelial tissues produce the two major classes of cationic AMPs (cAMPs), the defensins and cathelicidins. The largest reservoir of which is in the terminal layers of skin, potentially owing to the calcium gradient in human epidermis allowing the function of kallikrein, a cathelicidin processing enzyme in differentiated keratinocytes.[38] Human β-defensins (HBDs) 1 and 2 were found localized to sweat glands through immunohistochemistry;[39,40] however, there is uncertainty over their activity and relevance in this environment.[41] Cathelicidins are secreted from sweat glands, where they are active at very low concentrations despite low pH and high salt conditions.[40] Defensins and cathelicidins are amphipathic peptides that bind to the negatively charged cell membrane of staphylococci owing to electrostatic interactions. Subsequent aggregation of the peptides results in the formation of channels affecting membrane permeability.[42] Activity of the anionic dermcidin is independent of both staphylococcal membrane charge and peptide charge; dermcidin inhibits synthesis of RNA and protein.[41,43] The mechanism was proposed to depend on ion channel formation in the bacterial membrane stabilized by zinc ions.[44,45]

Lysozyme is present in many human fluids and secretions, and is produced by epithelial cells.[46] Many staphylococcal species are resistant to its N-acetylmuramoylhydrolase activity, including S. aureus, S. epidermidis, S. xylosus and S. lugdunensis. This resistance may be important for colonization of the skin.[47] Mutagenesis studies determined that the enzyme OatA, which O-acetylates peptidoglycan, is the major factor contributing to lysozyme resistance.[47] Moreover, oatA and dltA double mutants are highly sensitive to lysozyme and other cAMPs owing to the additional lack of D-alanine bound to teichoic acids.[48]

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