Bactericidal activity of the human skin fatty acid cis-6-hexadecanoic acid on Staphylococcus aureus.
Human skin fatty acids are a potent aspect of our innate defenses, giving surface protection against potentially invasive organisms. They provide an important parameter in determining the ecology of the skin microflora, and alterations can lead to increased colonization by pathogens such as Staphylococcus aureus. Harnessing skin fatty acids may also give a new avenue of exploration in the generation of control measures against drug-resistant organisms. Despite their importance, the mechanism(s) whereby skin fatty acids kill bacteria has remained largely elusive. Here, we describe an analysis of the bactericidal effects of the major human skin fatty acid cis-6-hexadecenoic acid (C6H) on the human commensal and pathogen S. aureus. Several C6H concentration-dependent mechanisms were found. At high concentrations, C6H swiftly kills cells associated with a general loss of membrane integrity. However, C6H still kills at lower concentrations, acting through disruption of the proton motive force, an increase in membrane fluidity, and its effects on electron transfer. The design of analogues with altered bactericidal effects has begun to determine the structural constraints on activity and paves the way for the rational design of new antistaphylococcal agents.
The Krebs Institute, Department of Molecular Biology and Biotechnology, University of Sheffield, Western Bank, Sheffield, United Kingdom.
Michaël L
ML
Cartron
Department of Chemistry, University of Sheffield, Brook Hill, Sheffield, United Kingdom.
Simon R
SR
England
Institute of Microbiology, Immunology and Parasitology, Medical Faculty, University of Bonn, Bonn, Germany.
Alina Iulia
AI
Chiriac
Institute of Microbiology, Immunology and Parasitology, Medical Faculty, University of Bonn, Bonn, Germany.
Michaele
M
Josten
The Krebs Institute, Department of Molecular Biology and Biotechnology, University of Sheffield, Western Bank, Sheffield, United Kingdom.
Robert
R
Turner
The Krebs Institute, Department of Molecular Biology and Biotechnology, University of Sheffield, Western Bank, Sheffield, United Kingdom.
Yvonne
Y
Rauter
The Krebs Institute, Department of Molecular Biology and Biotechnology, University of Sheffield, Western Bank, Sheffield, United Kingdom.
Alexander
A
Hurd
Institute of Microbiology, Immunology and Parasitology, Medical Faculty, University of Bonn, Bonn, Germany.
Hans-Georg
HG
Sahl
Department of Chemistry, University of Sheffield, Brook Hill, Sheffield, United Kingdom.
Simon
S
Jones
The Krebs Institute, Department of Molecular Biology and Biotechnology, University of Sheffield, Western Bank, Sheffield, United Kingdom s.foster@sheffield.ac.uk.
Simon J
SJ
Foster
D000255:Adenosine Triphosphate / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D024881:Drug Resistance, Bacterial; D004579:Electron Transport / Q000187:drug effects; D006801:Humans; D008081:Liposomes; D008560:Membrane Fluidity / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D019308:Palmitic Acid / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000494:pharmacology*; D058105:Polymerization; D012867:Skin / Q000737:chemistry*; D013211:Staphylococcus aureus / Q000187:drug effects*
D008081:Liposomes; D019308:Palmitic Acid; D000255:Adenosine Triphosphate