What is it about?
How does the fungus Candida albicans cause life-threatening catheter-associated urinary tract infections (CAUTIs)? Despite being very common, fungal CAUTIs have been neglected and thus little is known about the fungal factors that promote these infections. Here, using in vitro and in vivo models of CAUTI, we identified the key fungal genes necessary to form a CAUTI-relevant biofilm. Furthermore, we show that this group of genes are clinically relevant by validating them with catheters from actual human patients! Uncovering this tissue-specific genetic program provides a roadmap for targeted therapies and diagnostics to mitigate these life-threatening but neglected fungal infections.
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Why is it important?
There are various important findings in our work. First, we identified a bladder-specific fungal "virulence program." When Candida enters the bladder, it triggers expression of a specific network of genes, many of which were previously uncharacterized or had unknown functions. Second, we collected catheters from patients with fungal infections, preserving the pathogens at the moment of infection to sequence their active gene expression. The human data matched our laboratory findings, validating the "virulent programming" of Candida in the bladder and confirming that it was an active pathogen rather than a harmless colonizer or contaminant. Lastly, clinical infections (especially in hospital/catheter settings) are rarely caused by a single pathogen. They are usually polymicrobial, and our data clearly show that during these polymicrobial infections, the other microbes can have a positive or negative effect on Candida, affecting the expression of the fungal virulent genes driving the CAUTI.
Perspectives
This article is a continuation of a great collaboration with my long-time partner in research and in life, Dr. Flores-Mireles. We believe this research topic has a lot of potential implications for basic and clinical research, as well as for diagnostic improvements. In terms of basic research, why Candida is a common pathogen during catheterization but not in the absence of a catheter is not completely understood. Thus, this knowledge could help us understand why Candida, which is part of our normal flora (we all have it!), is harmless most of the times but can be lethal in other times. Because we all have Candida, clinicians often struggle to determine if Candida in a lab report represent active infection, sample contamination, or just asymptomatic colonization. By identifying specific virulence signatures/factors, this research provides a roadmap for diagnostics to confirm true active infections. We hope this research also highlight current diagnostic limits: standard diagnostic tools focus primarily on free-swimming Gram-negative bacteria in urine. Fungi and certain bacteria prefer attaching to surfaces (like catheters) rather than swimming, leading to underdiagnosis or misdiagnosis of fungal involvement. So we hope our work not only raise awareness of these infections but also provide important insights into how to overcome these limitations.
Felipe Santiago-Tirado
University of Notre Dame
Read the Original
This page is a summary of: The unique Efg1 fungal virulence regulon in the catheterized bladder environment, Proceedings of the National Academy of Sciences, July 2026, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2533309123.
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