Regulation of Hypervirulent Klebsiella pneumoniae Virulence by Environmental Signals in the Host

Project Summary/Abstract: Hypervirulent Klebsiella pneumoniae (hvKp) poses an urgent public health threat as a cause of severe infections, with growing concern due to emerging multidrug resistance. While intestinal colonization precedes most hvKp infections, the regulatory mechanisms controlling this crucial step remain poorly understood. Our preliminary data reveal that host-derived environmental cues in the gastrointestinal tract regulate hvKp capsule production and virulence genes, potentially orchestrating the transition from colonization to systemic infection. This R21 proposal will investigate how host signals coordinate hvKp gene expression during intestinal colonization and dissemination. We will define how these environmental cues regulate capsule production and virulence gene transcription through RNA sequencing and genetic approaches, focusing on their effects on virulence-associated phenotypes and host-pathogen interactions. This developmental research addresses a fundamental gap in understanding hvKp pathogenesis. By uncovering host-responsive pathways that orchestrate colonization and virulence, we will reveal novel therapeutic strategies against multidrug- resistant and hypervirulent K. pneumoniae, supporting future mechanistic studies and opening new avenues for preventing and treating life-threatening infections.