Viktória Lázár1, Gajinder Pal Singh1, Réka Spohn1, István Nagy2, Balázs Horváth2, Mónika Hrtyan1, Róbert Busa‐Fekete3, Balázs Bogos1, Orsolya Méhi1, Bálint Csörgő1, György Pósfai1, Gábor Fekete1, Balázs Szappanos1, Balázs Kégl3, Balázs Papp1, Csaba Pál1
1Synthetic and Systems Biology Unit, Institute of Biochemistry. Biological Research Center, Szeged. Hungary
2Genomics Unit, Institute of Biochemistry, Biological Research Center Szeged Hungary
3Linear Accelerator Laboratory, University of Paris-Sud, CNRS, Orsay, France
Tóm tắt
The evolution of resistance to a single antibiotic is frequently accompanied by increased resistance to multiple other antimicrobial agents. In sharp contrast, very little is known about the frequency and mechanisms underlying collateral sensitivity. In this case, genetic adaptation under antibiotic stress yields enhanced sensitivity to other antibiotics. Using large‐scale laboratory evolutionary experiments with Escherichia coli, we demonstrate that collateral sensitivity occurs frequently during the evolution of antibiotic resistance. Specifically, populations adapted to aminoglycosides have an especially low fitness in the presence of several other antibiotics. Whole‐genome sequencing of laboratory‐evolved strains revealed multiple mechanisms underlying aminoglycoside resistance, including a reduction in the proton‐motive force (PMF) across the inner membrane. We propose that as a side effect, these mutations diminish the activity of PMF‐dependent major efflux pumps (including the AcrAB transporter), leading to hypersensitivity to several other antibiotics. More generally, our work offers an insight into the mechanisms that drive the evolution of negative trade‐offs under antibiotic selection.
