A Role for LHC1 in Higher Order Structure and Complement Binding of the Cryptococcus neoformans Capsule

PLoS Pathogens

David Beenhouwer¹  Arturo Casadevall²  Radames J. B. Cordero³  Susana Frases³  Nannan Zhang³  John Panepinto⁴  John E. Bennett⁵  Patricia Albuquerque⁶  Yoon-Dong Park⁷  Peter R. Williamson⁷  Uwe Himmelreich⁷  Jin Qiu⁷  Jeanie Ramos⁸  Soowan Shin⁸ 

[1] Biomedical NMR Unit, Department of Medical Diagnostic Sciences, Division of Radiology, Katholieke Universiteit Leuven, Leuven, Belgium;Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, United States of America;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;Department of Microbiology and Immunology, University at Buffalo, the State University of New York, Buffalo, New York, United States of America;Division of Infectious Diseases, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California, 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;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

关键词: Cryptococcus neoformans;    Polysaccharides;    Phagocytosis;    Mutant strains;    Complement system;    Virulence factors;    Mouse models;    NMR spectroscopy;   

DOI  :  10.1371/journal.ppat.1004037

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY