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

## TL;DR

This study shows how the capsule in Klebsiella pneumoniae affects its ability to stick to cells, form biofilms, and survive inside host cells.

## Contribution

The study reveals a trade-off in capsule regulation between adhesion/biofilm formation and intracellular survival in K. pneumoniae.

## Key findings

- A wza knockout mutant showed increased biofilm formation, adhesion, and invasion compared to the encapsulated strain.
- Capsule absence increased surface negativity and exposure of adhesion structures, promoting host-cell interactions.
- The capsule provided an advantage for intracellular survival and replication.

## Abstract

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.