Evolution of antibiotic resistance

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

We have evolved several independent populations of methicillin-sensitive as well as methicillin-resistant S. aureus (MRSA) to multiple fluoroquinolones, and identified the adaptive trajectories leading to antibiotic resistance. We found that mutations in, and genomic amplifications of, a less-well characterized efflux pump lead to antibiotic resistance. The presence of the efflux pump increases the frequency of antibiotic resistance, and hitchhiking of additional efflux pumps in the amplification also leads to cross-resistance. We are currently characterizing the pathways required for the genomic amplifications, as well as the environmental factors that affect the selection of genomic amplifications upon antibiotic exposure.