Phylodynamic estimation of the within-host mutation rate of extended-spectrum beta-lactamase-producing Enterobacterales

Abstract

Despite their clinical relevance, the within-host evolution of extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE) is still poorly understood. To estimate the within-host mutation rates of ESBL-producing Escherichia coli and Klebsiella pneumoniae species complex, we fitted phylodynamic models to genomic sequence data of longitudinally collected rectal swabs from 64 colonized hospital patients. We estimated an average within-host mutation rate of 7.71e-07 [4.60e-07,1.10e-06] mutations/site/year for E. coli and 4.20e-07 [1.57e-07,7.14e-07] mutations/site/year for K. pneumoniae species complex, with limited variation observed across patients and sequence types. These estimates are presumably the most accurate reported so far and are useful for future epidemiological and evolutionary studies. Impact statementUnderstanding the within-patient mutation rates of extended-spectrum beta-lactamase (ESBL)-producing E. coli and K. pneumoniae species complex is critical for elucidating their evolutionary dynamics and transmission potential. In this study, we employed Bayesian phylodynamic models to analyze longitudinal isolates collected over a 10-year period from hospitalized patients. Our findings reveal limited variability in mutation rates across patients and sequence types, suggesting evolutionary stability within these pathogens in hospital settings. This work provides new insights into the persistence and evolutionary dynamics of ESBL-PE, offering valuable guidance for antimicrobial resistance surveillance and infection prevention strategies. Data summaryThe data used in this study are publicly available in the NCBI database under the BioProject number PRJNA910977. Supporting metadata are provided in Appendix 1. The code for the phylodynamic analyses, including the BEAST2 XML files, is available at https://github.com/EtthelWindels/esbl-pe_mutation. All supporting data, code and protocols have been provided within the article, supplementary data files or public repositories.