Capsular polysaccharide enables Klebsiella pneumoniae to evade phagocytosis by blocking host-bacteria interactions

Abstract

ABSTRACT Capsule polysaccharide (CPS) is among the most important virulence factors of Klebsiella pneumoniae. Previous studies demonstrated that CPS plays multiple functional roles, but the mechanism by which this virulence factor enhances the survival fitness of K. pneumoniae remains unclear. In this work, we demonstrate that CPS is the main cellular component that not only elicits the host immune response to K. pneumoniae but also enables this pathogen to survive for a prolonged period under adverse environmental conditions. Consistently, our in vitro experiments suggest that CPS prevents K. pneumoniae from phagocytosis, rendering the encapsulated strain more difficult to be eradicated by the host. We also found that phagocytosis of K. pneumoniae is partially mediated by LOX-1, a scavenger receptor of the host, and that CPS may impede interaction between LOX-1 and this pathogenic bacteria, therefore reducing the phagocytosis process. These findings provide insights into the pathogenic mechanisms of this important clinical pathogen and should facilitate the design of new strategies to combat K. pneumoniae infections.IMPORTANCEKlebsiella pneumoniae has become one of the most important clinical bacterial pathogens due to its evolution into hyperresistant and hypervirulent phenotypes. The mechanism of virulence of this pathogen is not well understood, particularly because it differs from other Enterobacteriaceae pathogens such as Escherichia coli and Salmonella. The capsule polysaccharide (CPS) of this pathogen is well recognized for contributing to the virulence of K. pneumoniae, but the exact mechanisms underlying its contribution are unclear. In this study, we demonstrated that CPS does not directly contribute to the host response; rather, it forms an external coat that blocks host recognition and prevents immune cells from binding to receptor proteins on K. pneumoniae, thus inhibiting phagocytosis, which makes it more challenging for the body to fight off infections. Understanding these mechanisms is vital for developing new treatments against K. pneumoniae infections, ultimately improving patient outcomes and public health.

Keywords

• Klebsiella pneumoniae
• virulence mechanisms
• capsular polysaccharide
• host recognition
• host response