Decreased susceptibility of Staphylococcus aureus small-colony variants toward human antimicrobial peptides.
Staphylococcus aureus is a frequent resident of human nose and skin in many individuals, but it is also able to cause a variety of serious infections including those of the skin and soft tissue. There is increasing evidence that particularly persistent, relapsing, and difficult-to-treat infections caused by S. aureus are associated with the formation of the small-colony variant (SCV) phenotype. The aim of this study was to investigate the hypothesis that (i) skin-derived antimicrobial peptides (AMPs) exhibit a reduced activity against SCVs and (ii) that switching into the SCV phenotype may endow S. aureus with a decreased susceptibility toward the killing activity of human stratum corneum. Here, we show that clinically derived S. aureus SCVs are less susceptible to the bactericidal activity of different human skin-derived AMPs as compared with their isogenic corresponding wild-type strains. Similarly, a S. aureus hemB mutant displaying the SCV phenotype was less susceptible to the antimicrobial activity of AMPs than its hemB-complemented mutant. These findings were accompanied by a higher resistance of SCVs to the killing activity of human stratum corneum. Switching into the SCV phenotype may help S. aureus to subvert cutaneous innate defense, thus contributing to the establishment and persistence of infection.
Department of Dermatology, University of Kiel, Kiel, Germany.
Regine
R
Gläser
Institute of Medical Microbiology, University Hospital of Münster, Münster, Germany.
Karsten
K
Becker
Institute of Medical Microbiology, University Hospital of Münster, Münster, Germany; Pfizer Pharma GmbH, Berlin, Germany.
Christof
C
von Eiff
Department of Dermatology, University of Kiel, Kiel, Germany.
Ulf
U
Meyer-Hoffert
Department of Dermatology, University of Kiel, Kiel, Germany. Electronic address: jharder@dermatology.uni-kiel.de.
Jürgen
J
Harder
D001426:Bacterial Proteins / Q000235:genetics* / Q000276:immunology*; D054804:Cathelicidins / Q000276:immunology / Q000378:metabolism; D023082:Defensins / Q000276:immunology* / Q000378:metabolism; D004198:Disease Susceptibility / Q000276:immunology; D004817:Epidermis / Q000276:immunology / Q000382:microbiology; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D010641:Phenotype; D012260:Ribonucleases / Q000276:immunology / Q000378:metabolism; D013207:Staphylococcal Skin Infections / Q000276:immunology* / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000235:genetics* / Q000276:immunology*; D023083:beta-Defensins / Q000276:immunology / Q000378:metabolism
D001426:Bacterial Proteins; D054804:Cathelicidins; C422950:DEFB103A protein, human; C106641:DEFB4A protein, human; D023082:Defensins; C585197:LL-37 peptide (17-32), human; D010446:Peptide Fragments; D023083:beta-Defensins; D012260:Ribonucleases; C470000:Ribonuclease 7