Chromosomal integration of blaCTX-M redefines the evolutionary trajectory of antibiotic resistance in E. coli through lineage-structured expansion
Danjean, M.; Morel-Journel, T.; Berti, V.; Benhadid-Brahmi, Y.; Gueye, S.; Lougbegnon, H. C.; Jacquier, H.; Denamur, E.; Bonacorsi, S.; Siguier, P.; Cornet, F.; Campos, M.; Petitjean, M.; Birgy, A.; Armand-Lefevre, L.
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The global CTX-M pandemic is considered a plasmid-driven phenomenon, yet chromosomal integration of blaCTX-M has been reported in various settings. Screening 451,174 publicly available E. coli genomes and retaining 2,269 CTX-M-E. coli long-read or hybrid assemblies, we found that 33.5% carried at least one chromosomally integrated blaCTX-M. Chromosomal integration was strongly structured by E. coli lineage and CTX-M variant, reaching 68.5% in ST38 and 43.9% in ST131. In the latter, integration rates varied between subclades with modelling, suggesting recent acceleration within the ST131-C2 subclade. Additional resistance genes were frequently co-integrated with blaCTX-M (33%), with architectures largely inherited from plasmid-borne structures. Integrations were mainly ISEcp1- or IS26-mediated (77.3% and 18.9%, respectively) and occurred across the entire E. coli chromosome without spared zones. blaCTX-M chromosomal integration is a widespread, lineage-structured component of the CTX-M pandemic, providing stable vertical inheritance that complements or may supplant plasmid-mediated dissemination in successful ESBL-E. coli clones.
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