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.