caa a22 4500 528785761 20190713030955.0 cr unu---uuuuu 180924s2014 xx s 000 0 eng 10.3929/ethz-b-000094815 doi 10.1038/ncomms5352 doi (ETHRESEARCH)oai:www.research-collection.ethz.ch:20.500.11850/94815 Genome-wide analysis captures the determinants of the antibiotic cross-resistance interaction network [Elektronische Daten] [Viktória Lázár, István Nagy, Réka Spohn, Bálint Csörgő, Ádám Györkei, Ákos Nyerges, Balázs Horváth, Andrea Vörös, Róbert Busa-Fekete, Mónica Hrtyan, Balazs; id_orcid 0000-0003-0253-7015 Bogos, Orsolya Méhi, Gergely Fekete, Balázs Szappanos, Balázs Kégl, Balázs Papp, Csaba Pál] Nat Commun Open access ethresearch 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. Creative Commons Attribution 4.0 International http://creativecommons.org/licenses/by/4.0 ethresearch Lázár Viktória joint author Nagy István joint author Spohn Réka joint author Csörgő Bálint joint author Györkei Ádám joint author Nyerges Ákos joint author Horváth Balázs joint author Vörös Andrea joint author Busa-Fekete Róbert joint author Hrtyan Mónica joint author Bogos Balazs; id_orcid 0000-0003-0253-7015 joint author Méhi Orsolya joint author Fekete Gergely joint author Szappanos Balázs joint author Kégl Balázs joint author Papp Balázs joint author Pál Csaba joint author Nature Communications London : Nature Publishing Group 5, p. 4352 2041-1723 http://hdl.handle.net/20.500.11850/94815 text/html WWW-Backlink auf das Repository (Open access) 1 Journal Article ethresearch ETHRESEARCH 856 40 http://hdl.handle.net/20.500.11850/94815 text/html WWW-Backlink auf das Repository (Open access) ETHRESEARCH 700 1- Lázár Viktória joint author ETHRESEARCH 700 1- Nagy István joint author ETHRESEARCH 700 1- Spohn Réka joint author ETHRESEARCH 700 1- Csörgő Bálint joint author ETHRESEARCH 700 1- Györkei Ádám joint author ETHRESEARCH 700 1- Nyerges Ákos joint author ETHRESEARCH 700 1- Horváth Balázs joint author ETHRESEARCH 700 1- Vörös Andrea joint author ETHRESEARCH 700 1- Busa-Fekete Róbert joint author ETHRESEARCH 700 1- Hrtyan Mónica joint author ETHRESEARCH 700 1- Bogos Balazs; id_orcid 0000-0003-0253-7015 joint author ETHRESEARCH 700 1- Méhi Orsolya joint author ETHRESEARCH 700 1- Fekete Gergely joint author ETHRESEARCH 700 1- Szappanos Balázs joint author ETHRESEARCH 700 1- Kégl Balázs joint author ETHRESEARCH 700 1- Papp Balázs joint author ETHRESEARCH 700 1- Pál Csaba joint author ETHRESEARCH 773 0- Nature Communications London : Nature Publishing Group 5, p. 4352 2041-1723 BK010053 XK010053 XK010000 ETHRESEARCH ETHRESEARCH ETHRESEARCH Journal Article Open access