[Show abstract][Hide abstract] ABSTRACT: Human skin fatty acids are a potent aspect of our innate defences, 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 colonisation by pathogens such as Staphylococcus aureus. Harnessing skin fatty acids may also give a new avenue to explore in the generation of control measures against drug resistant organisms. Despite their importance the mechanism(s) whereby skin fatty acids kill bacteria have 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 at lower concentrations C6H is still able to kill, acting via disruption of the proton motif force, an increase in membrane fluidity and 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 rational design of new antistaphylococcal agents.
Antimicrobial Agents and Chemotherapy 04/2014; · 4.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The iron-regulated surface determinant proteins (Isd) of Staphylococcus aureus are expressed during iron limitation and have been proposed to be involved in the scavenging of iron from heme. In this study, the genes encoding the surface proteins IsdA, IsdB, and IsdH were inactivated in order to determine their combined role. The triple mutant was found to have no defect in growth under any conditions of iron limitation tested. Also using a mouse septic arthritis model of S. aureus systemic disease, no significant difference in bacterial load was observed for the triple mutant, compared with its otherwise isogenic parent.