Improved Gene Ontology Annotation for Biofilm Formation, Filamentous Growth, and Phenotypic Switching in Candida albicans

Abstract

The opportunistic fungal pathogen Candida albicans is a significant medical threat, especially for immunocompromised patients. Experimental research has focused on specific areas of C. albicans biology, with the goal of understanding the multiple factors that contribute to its pathogenic potential. Some of these factors include cell adhesion, invasive or filamentous growth, and the formation of drug-resistant biofilms. The Gene Ontology (GO) (www.geneontology.org) is a standardized vocabulary that the Candida Genome Database (CGD) (www.candidagenome.org) and other groups use to describe the functions of gene products. To improve the breadth and accuracy of pathogenicity-related gene product descriptions and to facilitate the description of as yet uncharacterized but potentially pathogenicity-related genes in Candida species, CGD undertook a three-part project: first, the addition of terms to the biological process branch of the GO to improve the description of fungus-related processes; second, manual recuration of gene product annotations in CGD to use the improved GO vocabulary; and third, computational ortholog-based transfer of GO annotations from experimentally characterized gene products, using these new terms, to uncharacterized orthologs in other Candida species. Through genome annotation and analysis, we identified candidate pathogenicity genes in seven non-C. albicans Candida species and in one additional C. albicans strain, WO-1. We also defined a set of C. albicans genes at the intersection of biofilm formation, filamentous growth, pathogenesis, and phenotypic switching of this opportunistic fungal pathogen, which provides a compelling list of candidates for further experimentation.

A guide to best practices for Gene Ontology (GO) manual annotation

“…The work on biofilm and filamentous growth in Candida (28), heart development (29), a case study of focused curation for renal and cardiovascular research (30) and in depth curation of the peroxisome proteome in humans (31) will be instructive for learning about curation of the literature to create GO annotations.…”

Fungal Morphogenesis

“…For instance, genes and compounds that control morphogenesis often also control biofilm development (Giacometti et al 2011;Du et al 2012b;Tsang et al 2012;Connolly et al 2013;Fazly et al 2013). Not surprisingly, 68 out of the 122 genes that are involved in biofilm formation are also involved in filamentous growth in C. albicans (Inglis et al 2012). Some of these factors, such as Ras1, Cyr1/Cdc35, and Efg1, regulate Candida biofilm formation, filamentous growth, phenotypic switching, and pathogenesis (Inglis et al 2012).…”

“…Not surprisingly, 68 out of the 122 genes that are involved in biofilm formation are also involved in filamentous growth in C. albicans (Inglis et al 2012). Some of these factors, such as Ras1, Cyr1/Cdc35, and Efg1, regulate Candida biofilm formation, filamentous growth, phenotypic switching, and pathogenesis (Inglis et al 2012). In Cryptococcus, Znf2, the decision maker of the yeast to hypha transition and the mediator of the cryptococcal ability to cause disease, regulates more than half of the potential adhesins encoded in the genome LWang and X Lin, unpubl.).…”

Effect of tobacco tar on Staphylococcus aureus and Candida albicans biofilm formation

“…albicans adhesion and growth are particularly necessary for biofilm formation (Inglis et al, 2013;Silva et al, 2011). Our study showed that CSC significantly increased C. albicans adhesion and growth and promoted biofilm formation.…”