BACKGROUND: This study aimed to investigate the population heterogeneity on carbapenem susceptibility in Klebsiella pneumoniae strains that acquired a bla METHODS: A bla RESULTS: Introduction of pOXA-232 into carbapenem-susceptible K. pneumoniae strains resulted in two isogenic transformants with distinct resistance profiles: an unstable, high-level carbapenem-resistant (HCR), and highly virulent subpopulation
and a stable, low-level carbapenem-resistant (LCR), and low-virulence subpopulation. Whole genome and expression analyses revealed dysfunctionality of ompK36 in HCR subpopulations. Subculturing of HCR led to the re-emergence of heterogeneous populations with variations in carbapenem resistance and an additional compensatory mutation of 9,000 bp deletion in the genome. Thus, stable HCR strains featuring both mutations in ompK36 and compensatory mutations developed. CONCLUSION: This study demonstrated that underlying heterogeneity can promote the emergence of stable, high-level antibiotic resistance, even with the introduction of a plasmid carrying a low-level antibiotic resistance gene, such as bla