Viktória Lázár 1 , 5 , István Nagy 2 , 5 , Réka Spohn 1 , 5 , Bálint Csörgő 1 , Ádám Györkei 1 , Ákos Nyerges 1 , Balázs Horváth 2 , Andrea Vörös 2 , Róbert Busa-Fekete 3 , Mónika Hrtyan 1 , Balázs Bogos 1 , Orsolya Méhi 1 , Gergely Fekete 1 , Balázs Szappanos 1 , Balázs Kégl 4 , Balázs Papp a , 1 , Csaba Pál a , 1
08 July 2014
Understanding how evolution of antimicrobial resistance increases resistance to other drugs is a challenge of profound importance. By combining experimental evolution and genome sequencing of 63 laboratory-evolved lines, we charted a map of cross-resistance interactions between antibiotics in Escherichia coli, and explored the driving evolutionary principles. Here, we show that (1) convergent molecular evolution is prevalent across antibiotic treatments, (2) resistance conferring mutations simultaneously enhance sensitivity to many other drugs and (3) 27% of the accumulated mutations generate proteins with compromised activities, suggesting that antibiotic adaptation can partly be achieved without gain of novel function. By using knowledge on antibiotic properties, we examined the determinants of cross-resistance and identified chemogenomic profile similarity between antibiotics as the strongest predictor. In contrast, cross-resistance between two antibiotics is independent of whether they show synergistic effects in combination. These results have important implications on the development of novel antimicrobial strategies.
Understanding how evolution of antimicrobial resistance increases resistance to other drugs is of key importance. Here, Lazar et al. build a map of cross-resistance interactions between antibiotics in Escherichia coli and show that chemical and genomic similarities are good predictors of bacterial cross-resistance.