Dynamic genomic constraints reveal fitness trade-offs underlying bacterial resistance evolution

Postdoc Lucy Dillon, with James McInerney and Chris Creevey, combined pangenomic and machine-learning analyses of over 16,000 E. coli and Pseudomonas aeruginosa genomes to test whether antimicrobial resistance simply accumulates gene by gene. Instead, they found sets of resistance genes that are mutually exclusive within a species, evidence of fitness trade-offs that constrain which combinations of resistance mechanisms can coexist, and gene pairings that cooperate in E. coli but actively work against each other in P. aeruginosa. The findings reframe multidrug resistance evolution as following genomically constrained pathways rather than open-ended accumulation, highlighting new targets for follow-up work on resistance-associated fitness costs. Preprint available on bioRxiv.