Abstract
Uropathogenic Escherichia coli (UPEC) is the leading cause of urinary tract infection (UTI). While the role of UPEC in triggering host immune responses is well studied, less is known about how host-derived cytokines influence UPEC virulence. The aim of this study was to investigate how the pro-inflammatory cytokine IL-1β affects UPEC virulence, metabolism, and host-pathogen interactions. Using the CFT073 strain, we found that IL-1β exposure induced a rapid metabolic shift characterized by decreased oxygen consumption rate (OCR) and increased extracellular acidification rate (ECAR), indicating a transition from respiration to fermentative metabolism. Microarray analysis confirmed the upregulation of fermentative (hyc) and antioxidant (katG, ahpF, grxA) genes, along with increased purine biosynthesis, supporting a metabolic state favouring stress resistance and proliferation. IL-1β also increased fimH and papC gene expression, leading to increased adhesion and invasion of bladder epithelial cells. Furthermore, IL-1β-stimulated CFT073 suppressed the gene expression of several innate immune related genes in a C. elegans infection model. Taken together, our findings suggest that IL-1β induces a virulence-enhancing metabolic change in UPEC, which could enhance its persistence and colonization of the urinary tract. This cross-kingdom signaling may have implications for infection dynamics during a UTI.
Keywords:
C. elegans; Colonization; Cross-kingdom interaction; IL-1β; Uropathogenic E. coli.