The Staphylococcus aureus Surface Protein IsdA Mediates Resistance to Innate Defenses of Human Skin

Abstract

Resistance to human skin innate defenses is crucial for survival and carriage of Staphylococcus aureus, a common cutaneous pathogen and nasal colonizer. Free fatty acids extracted from human skin sebum possess potent antimicrobial activity against S. aureus. The mechanisms by which S. aureus overcomes this host defense during colonization remain unknown. Here, we show that S. aureus IsdA, a surface protein produced in response to the host, decreases bacterial cellular hydrophobicity rendering them resistant to bactericidal human skin fatty acids and peptides. IsdA is required for survival of S. aureus on live human skin. Reciprocally, skin fatty acids prevent the production of virulence determinants and the induction of antibiotic resistance in S. aureus and other Gram-positive pathogens. A purified human skin fatty acid was effective in treating systemic and topical infections of S. aureus suggesting that our natural defense mechanisms can be exploited to combat drug-resistant pathogens.

Neutrophil Microbicides Induce a Pathogen Survival Response in Community-Associated Methicillin-Resistant Staphylococcus aureus

“…Moreover, the data suggest heme-uptake is important for resistance to H 2 O 2 and/or that absence of IsdA and IsdB, major protein components of the cell envelope (56,57), alter properties of the cell envelope such that the bacterium has increased sensitivity to H 2 O 2 and/or components of innate host defense. Consistent with this idea, recent studies by Clarke et al (58) demonstrated that IsdA reduces surface hydrophobicity of S. aureus, thereby, rendering the pathogen more resistant to bactericidal fatty acids and peptides.…”

“…Percent S. aureus survival during interaction with neutrophils was determined using the equation (CFU ϩPMN at t/CFU ϩPMN at t0). altered heme-uptake or modification of the surface characteristics of staphylococci (58), thereby conferring increased susceptibility to peroxides and possibly other components of innate host defense.…”

Cutaneous Wound Healing after Topical Application of <i>Pistacia atlantica</i> Gel Formulation in Rats

“…11,12 Linoleic acid has also been shown to participate in cell proliferation and inflammatory process, where in the latter it plays a role as a mediator of leukocyte function having chemotactic and stimulatory effects on neutrophils. 13 Free fatty acids (FFAs) are known to possess anti-Staphylococcus aureus (S. aureus) activity 14,15,16 and are important components of the innate immune system. 17 These FFAs, including oleic acid, can function as innate bactericides.…”

Innate barriers against skin infection and associated disorders

“…The SA surface anchored IsdA protein, first studied in the context of iron acquisition, is now also known to reduce the overall hydrophobicity of the bacterium, thereby blocking the action of AMPs including cathelicidins and defensins, as well as the antibacterial properties of fatty acids present in human serum [38]. IsdA is upregulated by SA in vivo and in response to encountering neutrophils and their release of effector molecules such as oxidants and AMPs through the respiratory burst and degranulation.…”