Carleton University

Purpose

Antimicrobial resistance (AMR) is a serious and growing problem in the treatment of infectious disease. Broadly, the potential to use combat AMR using collateral sensitivity, a phenomenon whereby resistance to one antimicrobial results in sensitivity to other drugs will be examined. The hypothesis that collateral sensitivities can be used to slow the emergence of AMR will be tested. The central premise of this hypothesis is that the use of one drug will select against mutations that confer resistance to a second drug. For example, if streptomycin resistance mutations confer sensitivity to chloramphenicol, then treatment of a sensitive population of bacteria with chloramphenicol should slow the emergence of streptomycin resistance by selecting against specific, collaterally sensitive mutations. The team will test this hypothesis using a combination of conventional mutation rate assays and sequencing. This work will provide crucial tests of the central logic of using collateral sensitivity to fight AMR; such tests have not thus far been carried out.