Rapid evolution bacteria reveal pathogenic mechanisms and clinical risk

Abstract

Bacteria continually evolve, as postulated in Darwin’s theory of evolution1-3. Previous studies have evaluated bacterial evolution in retrospect, but this approach is based on only speculation4-6. Cohort studies are reliable but require a long duration7-11. Here, using hypermutable strains, we established a rapid and integrated bacterial evolution analysis, RIBEA, based on serial passaging experiments, whole-genome and transposon-directed sequencing, and in vivo evaluation to monitor bacterial evolution for one month in a cohort. RIBEA enabled the elucidation of the mechanism of clinical progression and the potential clinical risk associated with the development of invasive ability and antimicrobial resistance in the major respiratory pathogen Klebsiella pneumoniae12. RIBEA also revealed novel bacterial factors (via the identification of gene mutations that occurred during evolution) contributing to serum and antimicrobial resistance. Our results demonstrate that RIBEA enables the prediction of bacterial evolution and identification of clinically high-risk bacterial strains, clarifying the associated mechanisms of pathogenicity and antimicrobial resistance development.