A plasmid with the bla CTX-M gene enhances the fitness of Escherichia coli strains under laboratory conditions.

Abstract

Antimicrobial resistance (AMR) is a major threat to global public health that continues to grow owing to selective pressure caused by the use and overuse of antimicrobial drugs. Resistance spread by plasmids is of special concern, as they can mediate a wide distribution of AMR genes, including those encoding extended-spectrum β-lactamases (ESBLs). The CTX-M family of ESBLs has rapidly spread worldwide, playing a large role in the declining effectiveness of third-generation cephalosporins. This rapid spread across the planet is puzzling given that plasmids carrying AMR genes have been hypothesized to incur a fitness cost to their hosts in the absence of antibiotics. Here, we focus on a WT plasmid that carries the bla _{CTX-M 55} ESBL gene. We examine its conjugation rates and use head-to-head competitions to assay its associated fitness costs in both laboratory and wild Escherichia coli strains. We found that the wild strains exhibit intermediate conjugation levels, falling between two high-conjugation and two low-conjugation laboratory strains, the latter being older and more ancestral. We also show that the plasmid increases the fitness of both WT and lab strains when grown in lysogeny broth and Davis-Mingioli media without antibiotics, which might stem from metabolic benefits conferred on the host, or from interactions between the host and the rifampicin-resistant mutation we used as a selective marker. Laboratory strains displayed higher conjugation frequencies compared to WT strains. The exception was a low-passage K-12 strain, suggesting that prolonged laboratory cultivation may have compromised bacterial defences against plasmids. Despite low transfer rates among WT E. coli, the plasmid carried low fitness cost in minimal medium but conferred improved fitness in enriched medium, indicating a complex interplay between plasmids, host genetics and environmental conditions. Our findings reveal an intricate relationship between plasmid carriage and bacterial fitness. Moreover, they show that resistance plasmids can confer adaptive advantages to their hosts beyond AMR. Altogether, these results highlight that a closer study of plasmid dynamics is critical for developing a secure understanding of how they evolve and affect bacterial adaptability that is necessary for combating resistance spread.