Cefotaxime Exposure Selects Mutations within the CA-Domain of <i>envZ</i> Which Promote Antibiotic Resistance but Repress Biofilm Formation in Salmonella
Eleftheria Trampari, Chuan-Zhen Zhang, Kathryn Gotts, George M. Savva, Vassiliy N. Bavro, Mark Webber
Abstract
Understanding mechanisms of antibiotic resistance is crucial to guide how best to use antibiotics to minimize emergence of resistance. We used a laboratory evolution system to study how Salmonella responds to cefotaxime in both planktonic and biofilm conditions. In both contexts, we observed rapid selection of mutants within a single hot spot within envZ. The mutations selected altered EnvZ which in turn triggers changes in porin production at the outer membrane. Emergence of mutations within this region was repeatedly observed in parallel lineages in different conditions. We used a combination of genetics, biochemistry, phenotyping and structural analysis to understand the mechanisms. This data show that the changes we observe provide resistance to cefotaxime but come at a cost to biofilm formation and the fitness of mutants changes greatly depending on the presence or absence of a selective drug. Studying how resistance emerges can inform selective outcomes in the real world.