Virulence factors of Klebsiella pneumoniae: Insights into canonical and emerging mechanisms driving pathogenicity and drug resistance

Klebsiella pneumoniae used to cause nosocomial urinary tract infections, ventilator-associated pneumonia, surgical wound infections and bloodstream infections. Recently, it has emerged as a priority pathogen due to extensive drug resistance worldwide. These infections are a serious threat to neonates and immunocompromised patients, leading to substantial mortality and morbidity. Due to the parallel accumulation of multiple virulence factors, hypervirulent lineages of K. pneumoniae have emerged. These hypervirulent strains can cause community-acquired infections like pyogenic liver abscesses, meningitis, ophthalmitis, necrotizing fasciitis etc. With the development of advanced molecular technologies, next-generation sequencing, and the increasing availability of animal models of pathogenesis, a deeper understanding of the virulence factors and mechanisms of K. pneumoniae has become feasible. Some canonical virulence factors of this priority pathogen include capsular polysaccharides, lipopolysaccharides, iron-scavenging siderophores, outer membrane proteins, fimbriae, etc. which are largely defensive virulence factors allowing increased survival and immune evasion during various stages of the infection. In this review, we provide updated information on the canonical virulence factors of K. pneumoniae and also on the newly identified, non-canonical virulence factors of this pathogen, with an emphasis on the molecular mechanism of virulence. 1. Klebsiella pneumoniae causes severe infections including nosocomial urinary tract infections, ventilator-associated pneumonia, and surgical wound infections etc. 2. The drug resistance strains of K. pneumoniae is increasing worldwide. 3. A deeper understanding of the virulence factors and mechanisms of K. pneumoniae has been explained. 4. The molecular biology tools such as genomics and transcriptomics approach could be used to deeply study the K. pneumoniae host interactions to identify the potential candidates of virulence-related genes and their functional characterization • The updated information on the canonical and non-canonical virulence factors of K. pneumoniae has been described. • A clear understanding on the on the molecular mechanism of virulence. • Immunotherapy including active and passive immunization. • The emergence of antibiotic resistance strains. • The role of type VI secretion system in K. pneumoniae pathogenesis.