The mechanisms of evolution of antibiotic resistance in Staphylococcus aureus

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Staphylococcus aureus is one of the major resistant pathogens and, so far, it was able to acquire resistance to all antibiotics introduced into clinical practice. This grant application is focussed on the mechanisms involved in the evolution of resistance. Preliminary work has shown that exposure to antibiotics will not only select for resistant bacteria but may activate mutative mechanisms: In presence of ciprofloxacin and – to a lesser degree also in the presence of vancomycin – an increase in mutation frequency and an activation of mobile elements, e. g. IS-elements, was observed. The experiments proposed here will address the mechanisms involved in these processes. The major players include the SOS response and the response to cell wall inhibitory agents, the induction of error-prone polymerases, the regulation of the activity of stress sigma factor B and the regulation of transposition by antisense RNA. In addition, possible mutative effects of daptomycin and linezolid will be tested. The ultimate goal is to gain a detailed insight into these processes and thereby to increase the life-span of existing antibiotics.