Glycan microarray analysis of <i>Candida</i> -related antibodies in human and mice sera guides biomarker discovery and vaccine development
Abstract
Invasive, high-mortality yeast infections caused by pathogenic Candida species are the most common fungal nosocomial bloodstream infections. The World Health Organization (WHO) has called for improved prevention and diagnostic strategies for fungal pathogens. Here, we demonstrate that Candida -related antibodies can be detected using glycan microarrays containing synthetic glycans to guide the discovery of oligosaccharide epitopes for diagnostics and vaccine design. Pure, synthetic mannans and β -glucans, resembling carbohydrates found on the surface of Candida spp., were employed to screen and compare sera from infected humans and mice with noninfected individuals. IgM antibodies directed toward β -glucans were observed shortly after infection, and after a longer time of infection, IgM and IgG antibodies that preferentially recognize mannans. Phosphodiester-linked mannosides and the β -(1,2)-mannose monomer help to distinguish different Candida spp. The tetrasaccharide antigen β -(1,2)Man- α -(1,2)Man- α -(1,2)Man- α -(1,2)Man, and the pentasaccharide antigens α -(1,2)Man- α -(1,3)Man- α -(1,2)Man- α -(1,2)Man- α -(1,2)Man and β -(1,3)Glc- β -(1,3)Glc- β -(1,3)Glc-[ β -(1,6)Glc]- β -(1,3)Glc were identified as potential epitopes for detection, e.g., through monoclonal antibody lateral flow tests, and the development of glycoconjugate or monoclonal antibody vaccines against Candida.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (20)
Emelie E. Reuber
Department of Biomolecular Systems, Max-Planck-Institute of Colloids and Interfaces, Am Mühlenberg 1, 14476 Potsdam, Germany
Emer Hickey
Medical Research Council Centre for Medical Mycology at the University of Exeter, University of Exeter
Arnab Pradhan
Medical Research Council Centre for Medical Mycology at the University of Exeter, University of Exeter
Rosanne Sprute
Institute of Translational Research, Faculty of Medicine and University Hospital Cologne, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne
Tilman Lingscheid
Department of Infectious Diseases and Critical Care Medicine, Campus Virchow-Klinikum and Campus Charité Mitte, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität and Humboldt-Universität zu Berlin
Pinkus Tober-Lau
Department of Infectious Diseases and Critical Care Medicine, Campus Virchow-Klinikum and Campus Charité Mitte, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität and Humboldt-Universität zu Berlin
Ian Leaves
Medical Research Council Centre for Medical Mycology at the University of Exeter, University of Exeter
Mark H. T. Stappers
Medical Research Council Centre for Medical Mycology at the University of Exeter, University of Exeter
Florian Kurth
Department of Infectious Diseases and Critical Care Medicine, Campus Virchow-Klinikum and Campus Charité Mitte, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität and Humboldt-Universität zu Berlin
Mariolina Bruno
Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center
Mihai G. Netea
Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center
Leif E. Sander
Oliver A. Cornely
Institute of Translational Research, Faculty of Medicine and University Hospital Cologne, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne
Neil A. R. Gow
Alistair J. P. Brown
Medical Research Council Centre for Medical Mycology at the University of Exeter, University of Exeter
Rajat K. Singh
Institute of Chemistry and Biochemistry, Freie Universität Berlin
Sabrina Omoregbee-Leichnitz
Freie Universität Berlin
Eric T. Sletten
Biomolecular Systems Department, Max Planck Institute of Colloids and Interfaces
José Danglad-Flores
Max Planck Institute of Colloids and Interfaces
Peter H. Seeberger
Department of Biomolecular Systems, Max-Planck-Institute of Colloids and Interfaces, Am Muehlenberg 1, 14476 Potsdam, Germany