The unique Efg1 fungal virulence regulon in the catheterized bladder environment.

Abstract

Urinary catheterization, a frequent procedure in hospitals, nursing homes, and other healthcare facilities, is a primary driver of nosocomial infections. The most common of these are catheter-associated urinary tract infections (CAUTIs), which often progress to severe complication, sepsis, and ultimately death. The fungus <i>Candida albicans</i> is a primary causative agent of CAUTIs; yet, its tissue-specific pathogenesis remains poorly understood, which complicates development of efficient treatments. While Efg1 is a known virulence driver in CAUTI, its specific downstream targets within the unique bladder environment have not been defined. Here, we identify and validate the <i>EFG1</i> regulon that is active during conditions that mimic the human catheterized bladder and, additionally, confirm the regulon by transcriptional profiling of catheters retrieved from patients with <i>C. albicans</i> infection. We found that this urine-specific signature is highly conserved in clinical samples, with Efg1-dependent genes being among the most robustly induced transcripts during active human infection. Furthermore, we characterized two of these key factors, <i>ECE1</i> and <i>EED1</i>, validating their roles in infection both in vitro in human urine and in vivo using a CAUTI mouse model. Elucidating this tissue-specific regulon offers a strategic roadmap for the development of targeted therapies to mitigate these ever-increasing life-threatening fungal infections.