Glycomics-driven diagnostics for Candida auris

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Project Summary/Abstract Candida auris causes healthcare-associated fungal infections. C. auris colonizes the skin, ears (hence the designation ‘auris’), and other body sites. C. auris subsequent entry into the body leads to systemic infection and possible death. C. auris colonization of the human skin is difficult to eradicate despite chlorhexidine bathing and the persistence of the pathogen on inanimate objects in the hospitals and nursing homes requires use of bleach and sporicide disinfectants. There is a lack of mechanistic insight into the adherence properties of C. auris. Since 2013, there has been a surge of over 1,200 C. auris infections in the US, particularly in the New York metropolitan area. The New York State Department of Health (NYSDOH) documented 641 clinical cases and 849 screening cases from 151 healthcare facilities, including 59 hospitals and 92 nursing homes as of October 23, 2020. NYSDOH’s Wadsworth Center Mycology Laboratory (WC) and Division of Epidemiology developed and validated rapid, high-throughput PCR tests for C. auris, and innovated surveillance, admission screening, and point prevalence studies. The new PCR tests were distributed to NY hospital laboratories and also deployed by the Center for Disease Control (CDC) in other state and local public health laboratories. However, the availability of PCR tests remains restricted, and the results are available only after 24-48 h. Therefore, there is a gap in the laboratory capacity for the early detection of C. auris. The Linhardt Laboratory at the Rensselaer Polytechnic Institute (RPI) is known for its innovations in glycomics of infectious diseases and for devising unique diagnostic tools. The Linhardt and Chaturvedi Laboratories collaboratively found a unique C. auris mannan with distinct - 1,2 linkages, which are crucial for interactions with human IgG. This discovery will be expanded by devising a rapid glycan-based diagnostic test for C. auris. The proposed project has two aims: Aim 1 is to characterize the C. auris cell wall glycome from different clades and optimize glycan detection by SPR/MS methods. Aim 2 is to develop a C. auris immunochromatography assay (ICA) point-of-care test for swab, urine, and blood residual human specimens, and perform a validation compliant with the laboratory-developed test (LDT) requirements. This NIH R21 project has been designed to meet the fungal diagnostic innovation goals enunciated in NIH PA- 19-081.