RT Journal Article
SR Electronic
T1 Chance favors the prepared genomes: horizontal transfer shapes the emergence of antibiotic resistance mutations in core genes
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2023.06.20.545734
DO 10.1101/2023.06.20.545734
A1 Charles Coluzzi
A1 Martin Guillemet
A1 Fanny Mazzamurro
A1 Marie Touchon
A1 Maxime Godfroid
A1 Guillaume Achaz
A1 Philippe Glaser
A1 Eduardo PC Rocha
YR 2023
UL http://biorxiv.org/content/early/2023/06/22/2023.06.20.545734.abstract
AB Bacterial lineages vary in the frequency with which they acquire novel traits, like antibiotic resistance or virulence. While previous studies have highlighted the impact of the genetic background on the successful acquisition of novel traits through horizontal gene transfer, the impact of the latter on the subsequent evolution of bacterial genomes by point mutations remains poorly understood. Here, we studied the evolution of resistance to quinolones in thousands of Escherichia coli genomes. Resistance-conferring point mutations in the core genes are frequent and accumulate very quickly. We searched for gene gains and losses significantly associated with the subsequent acquisition of these resistance mutations. This revealed 60 groups of genes in genetic linkage whose gain or loss induced a change in the probability of subsequently becoming resistant to quinolones by point mutations in gyrA and parC. Although some of these chronologies may reflect epidemiological trends, most of these groups encoded functions that were previously associated with antibiotic resistance, tolerance, or persistence, often specifically under quinolone treatment. A lot of the largest groups were found in prophages or plasmids, and they usually increased the likelihood of subsequent resistance mutations. Conversely groups of lost genes were typically small and chromosomal. Quinolone resistance was among the first resistances acquired in the extant lineages of E. coli and its acquisition was associated with an increased likelihood of acquiring other types of resistances, including to aminoglycosides and beta-lactams. Our findings suggest that gene flow shapes the subsequent fixation rate of adaptive mutations in core genes. Given the substantial gene flow within bacterial genomes, interactions between horizontal transfer and point mutations in core genes may be key to the success of adaptation processes.Competing Interest StatementThe authors have declared no competing interest.