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Cell wall mannans of Candida albicans mask β-(1,3)-glucan from recognition by Dectin-1, contributing to innate immune evasion. Glucan exposures are predominantly single receptor-ligand interaction sites of nanoscale dimensions. Candida species vary in basal glucan exposure and molecular complexity of mannans. We used super-resolution fluorescence imaging and a series of protein mannosylation mutants in C. albicans and C. glabrata to investigate the role of specific N-mannan features in regulating the nanoscale geometry of glucan exposure. Decreasing acid labile mannan abundance and α-(1,6)-mannan backbone length correlated most strongly with increased density and nanoscopic size of glucan exposures in C. albicans and C. glabrata, respectively. Additionally, a C. albicans clinical isolate with high glucan exposure produced similarly perturbed N-mannan structures and elevated glucan exposure geometry. Thus, acid labile mannan structure influences the nanoscale features of glucan exposure, impacting the nature of the pathogenic surface that triggers immunoreceptor engagement, aggregation, and signaling.

mannan, Microscopy, Candida albicans, Mannosyltransferase, Candida glabrata, dSTORM, glucan exposure, quantitative image analysis, super resolution

NCBI PubMed ID: 30157435
Publication DOI: 10.1016/j.celrep.2018.07.088
Journal NLM ID: 101573691
Publisher: Cambridge, MA: Cell Press
Correspondence: Neumann AK salud.unm.edu>
Institutions: Department of Surgery, Quillen College of Medicine, East Tennessee State University, Johnson City, USA, AppRidge International, LLC, Telford, TN, USA, Department of Pathology, University of New Mexico, Albuquerque, USA, Department of Mathematics and Statistics, University of New Mexico, Albuquerque, USA, European Molecular Biology Laboratory (EMBL), Australia Node in Single Molecule Science, School of Medical Sciences, University of New South Wales, Sydney, Australia, Center of Excellence in Inflammation, Infectious Disease and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson City, USA, Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, USA, Department of Physics and Astronomy, University of New Mexico, Albuquerque, USA
Methods: 1H NMR, genetic methods, flow cytometry, centrifugation, COSY, alkali extraction, GPC-MALLS, statystical analysis