Bactericidal Activity of the Human Skin Fatty Acid cis-6-Hexadecanoic Acid on Staphylococcus aureus

• Published in: Antimicrobial agents and chemotherapy Vol. 58; no. 7; pp. 3599 - 3609
• Main Authors: CARTRON, Michaël L, ENGLAND, Simon R, CHIRIAC, Alina Iulia, JOSTEN, Michaele, TURNER, Robert, RAUTER, Yvonne, HURD, Alexander, SAHL, Hans-Georg, JONES, Simon, FOSTER, Simon J
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for Microbiology 01.07.2014
• Subjects: Adenosine Triphosphate - metabolism; Antibiotics. Antiinfectious agents. Antiparasitic agents; Bacterial diseases; Biological and medical sciences; Cell Membrane Permeability - drug effects; Drug Resistance, Bacterial; Electron Transport - drug effects; Human bacterial diseases; Humans; Infectious diseases; Liposomes; Mechanisms of Action: Physiological Effects; Medical sciences; Membrane Fluidity - drug effects; Membrane Potentials - drug effects; Microbial Sensitivity Tests; Palmitic Acid; Palmitic Acid - antagonists & inhibitors; Palmitic Acid - chemistry; Palmitic Acid - pharmacology; Pharmacology. Drug treatments; Polymerization; Skin; Skin - chemistry; Staphylococcal infections, streptococcal infections, pneumococcal infections; Staphylococcus aureus; Staphylococcus aureus - drug effects; Human; Lipids; Fatty acids; Biological activity; Infection; Bacteriosis; Bacteria; Micrococcales; Micrococcaceae; Skin; Antibacterial agent; Staphylococcal infection; Staphylococcus aureus
• ISSN: 0066-4804; 1098-6596
• DOI: 10.1128/AAC.01043-13

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.