Position title: Integrated Program in Biochemistry
- Katherine Henzler-Wildman
Inducing susceptibility with a Small Multidrug Resistance Transporter in P. aeruginosa
The Small Multidrug Resistance transporters are among the smallest known multidrug efflux pumps, and remove toxic compounds including many antiseptics from multidrug-resistant pathogens. SMRs may induce susceptibility to some compounds rather than resistance, either through direct influx/symport or by rundown of the proton-motive force (PMF) through uncontrolled proton uniport. PAsmr, an SMR from P. aeruginosa, has been shown to confer resistance to some known SMR substrates in vivo and in vitro, but has not been further investigated as a potential mechanism to induce susceptibility. I hypothesize that the phenotype of PAsmr in vivo is substrate-dependent, potentially conferring susceptibility to some compounds. I have demonstrated that PAsmr displays both resistance and susceptibility phenotypes, depending on substrate, in vivo. This constitutes an advance in our understanding of underlying resistance mechanisms in P. aeruginosa, and prompts further investigation into the role that SMRs play in antibiotic resistance in pathogens.