Elucidating the role of fimbriae in Klebsiella pneumoniae-mediated liver abscess formation

Classical Klebsiella pneumoniae (cKp) isolates are typically associated with hospital-acquired infections such as pneumonia, bacteremia, and urinary tract infections (UTIs) in immunocompromised patients. Over the past thirty years, a distinct pathotype known as hypervirulent Klebsiella pneumoniae (hvKp) has emerged, recognized for causing severe infections, including liver abscesses, in otherwise healthy individuals. Despite the availability of targeted antibiotic therapies, hvKp infections can escalate into severe complications such as endophthalmitis and meningitis. Previous mouse infection models have demonstrated that hvKp evades clearance by Kupffer cells in the liver sinusoids, highlighting a critical gap in our understanding of hvKp virulence mechanisms. However, due to rapid mortality in experimental models, the bacterial factors required for liver abscess formation remain underexplored. We have established a novel mouse hvKp wound infection model which progresses to systemic infection, including the formation of macroabscesses in the liver. Initial findings indicate that a mutant deficient in both the type 1 and type 3 fimbriae is unable to form liver abscesses but retains virulence in the wound and the kidney. Fimbriae are surface expressed protein appendages that play a crucial role in the infection process. Type 1 fimbriae in cKp strains bind mannose residues on uroepithelial cells to mediate urinary tract infections (UTIs). Type 3 fimbriae mediate biofilm formation and facilitate attachment to abiotic catheters in a UTI model. However, Klebsiella fimbriae are dispensable for gut and lung colonization and their contribution to liver abscesses is unknown. In this study, we will investigate the specific contributions of type 1 and type 3 fimbriae to the pathogenesis process and evaluate their potential as targets for therapeutic intervention. Our methods include constructing and evaluating the ability of hvKp strains lacking type 1 and/or type 3 fimbriae to infect mouse wounds, disseminate from the wound and establish liver abscesses. We anticipate that strains deficient in these fimbriae will demonstrate significantly reduced liver colonization, underscoring their importance in hvKp pathogenicity. This investigation will significantly advance our understanding of hvKp virulence strategies in liver abscess formation and may lead to the development of novel anti-virulence therapies.