A role for LHC1 in higher order structure and complement binding of the Cryptococcus neoformans capsule.
Polysaccharide capsules are important virulence factors for many microbial pathogens including the opportunistic fungus Cryptococcus neoformans. In the present study, we demonstrate an unusual role for a secreted lactonohydrolase of C. neoformans, LHC1 in capsular higher order structure. Analysis of extracted capsular polysaccharide from wild-type and lhc1Δ strains by dynamic and static light scattering suggested a role for the LHC1 locus in altering the capsular polysaccharide, both reducing dimensions and altering its branching, density and solvation. These changes in the capsular structure resulted in LHC1-dependent alterations of antibody binding patterns, reductions in human and mouse complement binding and phagocytosis by the macrophage-like cell line J774, as well as increased virulence in mice. These findings identify a unique molecular mechanism for tertiary structural changes in a microbial capsule, facilitating immune evasion and virulence of a fungal pathogen.
Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Yoon-Dong
YD
Park
Section of Infectious Diseases, Department of Medicine, University of Illinois at Chicago College of Medicine, Chicago, Illinois, United States of America.
Soowan
S
Shin
Department of Microbiology and Immunology, University at Buffalo, the State University of New York, Buffalo, New York, United States of America.
John
J
Panepinto
Section of Infectious Diseases, Department of Medicine, University of Illinois at Chicago College of Medicine, Chicago, Illinois, United States of America.
Jeanie
J
Ramos
Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Jin
J
Qiu
Department of Microbiology and Immunology and Division of Infectious Diseases of the Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, New York, United States of America; Laboratorio de Ultraestrutura Cellular Hertha Meyer, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Susana
S
Frases
Department of Microbiology and Immunology and Division of Infectious Diseases of the Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, New York, United States of America.
Patricia
P
Albuquerque
Department of Microbiology and Immunology and Division of Infectious Diseases of the Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, New York, United States of America.
Radames J B
RJ
Cordero
Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Nannan
N
Zhang
Biomedical NMR Unit, Department of Medical Diagnostic Sciences, Division of Radiology, Katholieke Universiteit Leuven, Leuven, Belgium.
Uwe
U
Himmelreich
Division of Infectious Diseases, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California, United States of America; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, United States of America.
David
D
Beenhouwer
Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
John E
JE
Bennett
Department of Microbiology and Immunology and Division of Infectious Diseases of the Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, New York, United States of America.
Arturo
A
Casadevall
Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America; Section of Infectious Diseases, Department of Medicine, University of Illinois at Chicago College of Medicine, Chicago, Illinois, United States of America.
Peter R
PR
Williamson
D000818:Animals; D002478:Cells, Cultured; D003165:Complement System Proteins / Q000378:metabolism*; D003453:Cryptococcosis / Q000276:immunology / Q000382:microbiology; D003455:Cryptococcus neoformans / Q000276:immunology* / Q000378:metabolism* / Q000472:pathogenicity / Q000648:ultrastructure; D062607:Fungal Capsules / Q000276:immunology* / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D006867:Hydrolases / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D040901:Proteomics; D014774:Virulence / Q000235:genetics
D003165:Complement System Proteins; D006867:Hydrolases