Publication Details
Abstract
Multidrug-resistant (MDR) Klebsiella pneumoniae has developed into an alarming public health concern worldwide, especially in hospitals, where its ability to resist treatment leads to increased morbidity and mortality. Here, we performed comprehensive characterizations of the genomic determinants and resistance mechanisms contributing to the emergence of multidrug resistant (MDR) K. pneumoniae, with particular attention on resistance islands (RIs). RIs are genomic regions that contain multiple antimicrobial resistance (AMR) genes, which is critical to the parasite adaptation mechanism to respond to antibiotic pressure. K. pneumoniae isolates undergoing whole-genome sequencing (WGS) to identify and characterize RIs, antimicrobial resistance (AMR) genes, and mobile genetic elements, including transposons and integrons, associated with horizontal gene transfer. A comparative genomic analysis showed a diverse repertoire of RIs encoding resistance to β-lactams, aminoglycosides, fluoroquinolones and carbapenems. Importantly, integrative and conjugative elements (ICEs) were commonly identified as vehicles for the dissemination of RIs, underscoring their crucial contribution to the rapid uptake of resistance determinants. Functional assays validated phenotypic resistance, correlating with genomic predictions. In addition, phylogenetic analysis demonstrated a sufficiently high clonal diversity to highlight the complexity of MDR K. pneumoniae epidemiology and dynamics of resistance development. This study highlights the significance of genomic surveillance for detection of central resistance determinants in addition to monitoring the spread of MDR K. pneumoniae. Our results provide insight into RI architecture and mobility and inform targeted antimicrobial stewardship efforts and where to develop innovative therapies to counter this daunting pathogen.