Genomic and phenotypic heterogeneity of Klebsiella aerogenes in a single host: plasmid loss and tissue-specific virulence gene expression during host adaptation.

Klebsiella aerogenes is an opportunistic pathogen increasingly associated with healthcare-associated infections and severe respiratory complications. However, it's in vivo adaptation during host colonization remains poorly understood. We characterized three clonal K. aerogenes ST93 isolates sequentially recovered on days 4, 14, and 19 of hospitalization from a patient with fatal viral pneumonia and concurrent abdominal sepsis. While initially identified generically as Klebsiella spp. by automated clinical systems, Whole-Genome Sequencing and Average Nucleotide Identity confirmed their identity at the species level. Genomic analysis revealed an in vivo plasmid curing event characterized by the loss of a 6.1 kb blaOXA-232-carrying plasmid in the final isolate (18281). Despite this plasmid loss, isolate 18281 sustained persistent carbapenem resistance due to a conserved ompK36 chromosomal mutation. Phenotypically, 18281 exhibited significantly higher lethality in Galleria mellonella larvae and induced progressive body weight loss in dexamethasone-treated mice compared to the other isolates. This enhanced virulence strongly correlated with a tissue-specific, compartmentalized transcriptional reprogramming, characterized by a marked 15.66-fold up-regulation of the yersiniabactin gene irp1 within hepatic tissues, whereas the colibactin gene clbA was consistently downregulated in vivo across both isolates and organs. Our findings demonstrate that intra-host microevolution of K. aerogenes involves structural plasmid instability and targeted transcriptional remodeling during host adaptation. This localized adaptive behavior underscores the clinical threat posed by transitional clonal variants in critically ill patients undergoing viral-mediated immune dysregulation.