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Regulation of Candida albicans Central Venous Catheter Biofilms by Transcription Factor Networks

Award Number: R21AI193658
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/15/2026
PERIOD OF PERFORMANCE END DATE: 05/31/2028

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Regulation of Candida albicans Central Venous Catheter Biofilms by Transcription Factor Networks - PROJECT SUMMARY/ABSTRACT Biofilms contribute to over 80% of microbial infections. Candida albicans biofilms, particularly those forming on indwelling medical devices such as central venous catheters (CVCs), are a major source of disseminated bloodstream infections. While in vitro studies have defined core biofilm regulators, they fail to recapitulate the complexity of clinical environments where CVCs are exposed to continuous blood flow and vascular host surfaces. Consequently, key regulators of biofilm formation under these conditions remain elusive. To address this gap, we utilize a clinically relevant jugular vein catheter mouse model, in which C. albicans biofilms form under physiological bloodstream conditions. Complementing this, we have developed a human-relevant ex vivo vascularized catheter system using silicone catheter material preconditioned with plasma and seeded with human endothelial cells to simulate the host-device interface. Preliminary screening of C. albicans transcription factor (TF) mutants revealed that several canonical regulators of in vitro biofilm formation (BCR1, BRG1, ROB1) are dispensable in vivo. Notably, we identified novel regulators, including PHO4 and CAS5, that are essential for vascular biofilm growth and were not previously linked to this process. We hypothesize that distinct, context- specific transcriptional circuits govern CVC biofilm formation in vivo and can only be uncovered through direct investigation in host-relevant systems. In Aim 1, we will conduct a comprehensive screen of ~155 barcoded TF mutants in vivo to identify regulators critical for biofilm growth on CVCs, followed by secondary validation in the vascularized ex vivo model. In Aim 2, we will define the downstream effector genes and regulatory circuits controlled by these TFs using transcriptomic profiling and targeted mutant analysis. Importantly, this tiered strategy prioritizes validation in human-relevant models and limits in vivo experiments, in full alignment with the NIH’s policy promoting New Approach Methodologies (NAMs) to reduce animal use. This research will yield high-resolution insights into vascular biofilm regulation and uncover novel, clinically actionable targets to prevent or treat catheter-associated bloodstream infections.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $449,625 )
2026	2026	LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER	1124 W CARSON ST BLDG MRL	TORRANCE	CA	90502	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	1	6/16/2026	NEW	$449,625
														Subtotal = $449,625

Grand Total All Awards = $449,625

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Regulation of Candida albicans Central Venous Catheter Biofilms by Transcription Factor Networks

Award Number: R21AI193658

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 06/15/2026

PERIOD OF PERFORMANCE END DATE: 05/31/2028

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