Rapid Evolution of Colistin Resistance in a Bioreactor Model of Infection of Klebsiella pneumoniae

Colistin resistance remains an important antibiotic for the therapeutic management of drug-resistant Klebsiella pneumoniae. Despite the numerous reports of colistin resistance in clinical strains, it remains unclear exactly when and how different mutational events arise resulting in reduced colistin susceptibility. Using a bioreactor model of infection, we modelled the emergence of colistin resistance in a susceptible isolate of K. pneumoniae. Genotypic, phenotypic and mathematical analyses of the antibiotic challenged and un-challenged population indicates that after an initial decline, the population recovers within 24h due to a small number of “founder cells” which have single point mutations mainly in the regulatory genes encoding crrB and pmrB and whose phenotype exhibits colistin MICs up to 100-fold higher than the parental strain. Our work underlines that development of colistin resistance during treatment of susceptible K. pneumoniae infections is readily achieved having implications for the use of cationic antimicrobial peptides as a monotherapy. The dataset is related to the paper 'Rapid Evolution of Colistin Resistance in a Bioreactor Model of Infection of Klebsiella pneumoniae' (https://doi.org/10.1101/2022.10.03.510619).