Capsule Regulation Shapes Klebsiella pneumoniae Pathogenesis by Balancing Adhesion, Biofilm Formation, and Intracellular Survival

Klebsiella pneumoniae is a major opportunistic pathogen, where the polysaccharide capsule is traditionally recognized as a critical virulence determinant. However, its role in surface interactions and intracellular adaptation remains incompletely understood. Here, we combined phenotypic assays with physicochemical analyses to dissect the contribution of the capsule. A wza knockout mutant displayed enhanced biofilm formation, adhesion, and invasion of epithelial cells compared to the encapsulated strain. Zeta potential and hydrodynamic size measurements revealed that capsule absence increased surface negativity and exposure of adhesion structures, thereby promoting host–cell interactions. In contrast, intracellular survival assays demonstrated that the capsule conferred a clear advantage for persistence and replication. Together, our results support a dynamic model in which capsule expression imposes a trade-off: restricting early adhesion and biofilm development but favoring long-term intracellular survival. This trade-off model expands the understanding of capsule biology and may inform novel strategies to disrupt colonization or persistence in antibiotic-resistant K. pneumoniae.