Virulence and antimicrobial resistance in hypervirulent Klebsiella pneumoniae: molecular mechanisms and emerging therapeutic strategies

Klebsiella pneumoniae is a ubiquitous opportunistic pathogen distributed across diverse environments, ranging from natural ecosystems to clinical settings. It has emerged as a major global health threat due to the rapid spread of multidrug-resistant lineages through horizontal gene transfer. MDR K. pneumoniae is associated with both community and hospital-acquired infections with substantial morbidity and mortality. In recent years, carbapenem-resistant K. pneumoniae has been recognized as a critical priority pathogen by the World Health Organization (WHO). The mechanisms of antimicrobial resistance in K. pneumoniae are complex and are likely to be due to multiple resistance mechanisms or pathways simultaneously. Key contributors include enzymatic degradation of antibiotics by extended-spectrum beta-lactamases and carbapenemases, reduced membrane permeability due to alterations in outer membrane porins, and active efflux systems. Besides these, bacteria can transiently adjust gene expression to survive antibiotic and host-induced stress. In addition to resistance, hypervirulence further complicates the available treatment options. Hypervirulent K. pneumoniae (hvKP) strains possess a range of factors that enhance pathogenicity, including a robust capsule, hypermucoviscosity, adhesion molecules, efficient iron acquisition systems, and toxin expression. These features enable effective colonization, proliferation within host tissues, and evasion of host immune defences. Biofilm formation is another virulence factor that provides a protective niche from antimicrobial agents, particularly on indwelling medical devices. Moreover, co-transmission of virulence and drug-resistant genes substantially complicates the control of hvKP infections. This review provides an overview of the molecular basis of virulence and antimicrobial resistance in hvKP and explores emerging therapeutic approaches to combat these infections.