title: 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.
authors.affiliation: Department of Molecular Biology and Biotechnology, University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN, UK.
authors.forename: Simon R
authors.initials: SR
authors.lastname: Clarke
authors.forename: Ramlan
authors.initials: R
authors.lastname: Mohamed
authors.forename: Li
authors.initials: L
authors.lastname: Bian
authors.forename: Alexander F
authors.initials: AF
authors.lastname: Routh
authors.forename: John F
authors.initials: JF
authors.lastname: Kokai-Kun
authors.forename: James J
authors.initials: JJ
authors.lastname: Mond
authors.forename: Andrej
authors.initials: A
authors.lastname: Tarkowski
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Foster
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000942:Antigens, Bacterial / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology; D015169:Colony Count, Microbial; D005227:Fatty Acids / Q000302:isolation & purification / Q000494:pharmacology; D006460:Hemolysin Proteins / Q000096:biosynthesis; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D050296:Microbial Viability; D012629:Sebum / Q000276:immunology / Q000382:microbiology; D012867:Skin / Q000737:chemistry / Q000276:immunology* / Q000382:microbiology; D013207:Staphylococcal Skin Infections / Q000188:drug therapy / Q000276:immunology*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D037521:Virulence Factors / Q000096:biosynthesis
chemical_list: D000900:Anti-Bacterial Agents; D000942:Antigens, Bacterial; D023181:Antimicrobial Cationic Peptides; D005227:Fatty Acids; D006460:Hemolysin Proteins; C512791:IsdA protein, Staphylococcus aureus; D037521:Virulence Factors