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Molecular Mechanisms of Candida auris Adhesion to Abiotic Surfaces

Award Number: F31AI169823
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 02/01/2023
PERIOD OF PERFORMANCE END DATE: 02/29/2024

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Molecular Mechanisms of Candida auris Adhesion to Abiotic Surfaces - Abstract Candida auris is an emerging fungal pathogen responsible for invasive, often multidrug-resistant infections and outbreaks worldwide. Unlike for many other fungal pathogens, C. auris infection is primarily nosocomial, driven by the propensity of C. auris to robustly colonize medical devices, implants, and abiotic surfaces that are proximal to patient quarters. C. auris can survive on abiotic surfaces for weeks, and many strains are resistant to commonly used antifungals and disinfectants, hindering decontamination efforts. The importance of this colonization to C. auris disease spread is demonstrated by intervention case studies associating reduction of infection incidence with removal of colonized fomites. C. auris can also form biofilms on surfaces, likely contributing to its resistance to decontamination. On a molecular scale, these processes require the initial first step of individual fungal cells physically attaching to a surface. While the regulation of attachment has been explored to a limited extent in related fungal species, no mechanistic studies have investigated the molecular machinery governing initial attachment in C. auris. Furthermore, while C. auris encodes genes homologous to characterized Candida albicans ALS and IFF/HYR family adhesins, proteins which have been implicated in attachment in other fungal species, our findings indicate none of these genes substantially contributes to attachment to abiotic surfaces in C. auris. Instead, we have identified B9J08_001458, a novel class of adhesin specifically encoded by C. auris with no characterized homologs. Deletion of B9J08_001458 substantially and significantly reduces C. auris adhesion. Furthermore, our preliminary findings suggest natural transcriptional variation of B9J08_001458 among C. auris isolates is linked to natural variation in adhesive potential. The goal of this proposal is to identify the functional and regulatory mechanisms of C. auris adhesion and explain the variability in adhesion in different C. auris clinical isolates. Our hypothesis is that C. auris regulates an adhesive cell surface profile primarily through expression of the putative novel adhesin B9J08_001458, and that transcriptional control of this adhesin explains adhesive variation amongst C. auris isolates. To address this hypothesis, we will leverage our global genetic and transcriptomic datasets to identify transcription factors targeting B9J08_001458. Our findings also suggest B9J08_001458 is regulated through the SWI/SNF chromatin remodeling complex; we will characterize this layer of transcriptional regulation by comparing chromatin states between wild type cells and mutants deficient in SWI/SNF function. We will then investigate the impact of genetic variants driving differential expression of B9J08_001458 amongst diverse C. auris isolates using genome wide association studies. The findings of this proposal will provide a scientific foundation for the rational development of decontamination and infection control protocols against C. auris, potentially mitigating the disease burden of this fungus.


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: 2025 ( Subtotal = -$32,247 )
2025	2024	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Allergy and Infectious Diseases Research	000	2	10/10/2024	NON-COMPETING CONTINUATION	-$28,247
2025	2024	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE STE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Allergy and Infectious Diseases Research	001	2	12/20/2024	NON-COMPETING CONTINUATION	-$4,000
														Subtotal = -$32,247

Issue Date FY: 2024 ( Subtotal = $42,574 )
2024	2024	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Allergy and Infectious Diseases Research	001	2	7/22/2024	NON-COMPETING CONTINUATION	$42,574
2024	2023	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Allergy and Infectious Diseases Research	000	1	6/14/2024	NEW	$0
														Subtotal = $42,574

Issue Date FY: 2023 ( Subtotal = $41,294 )
2023	2023	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON STREET	ANN ARBOR	MI	48109	WASHTENAW	USA	Allergy and Infectious Diseases Research	001	1	2/24/2023	NEW	$942
2023	2023	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Allergy and Infectious Diseases Research	000	1	11/16/2022	NEW	$40,352
														Subtotal = $41,294

Grand Total All Awards = $51,621

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Molecular Mechanisms of Candida auris Adhesion to Abiotic Surfaces

Award Number: F31AI169823

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 02/01/2023

PERIOD OF PERFORMANCE END DATE: 02/29/2024

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