Open AccessA Role for LHC1 in Higher Order Structure and Complement Binding of the Cryptococcus neoformans Capsule
Author(s) -
Yoon Dong Park,
Soowan Shin,
John C. Panepinto,
Jeanie Ramos,
Jin Qiu,
Susana Frasés,
Patrícia Albuquerque,
Radamés J. B. Cordero,
Nannan Zhang,
Uwe Himmelreich,
David O. Beenhouwer,
John E. Bennett,
Arturo Casadevall,
Peter R. Williamson
Publication year - 2014
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1004037
Subject(s) - cryptococcus neoformans , virulence , microbiology and biotechnology , biology , phagocytosis , cryptococcosis , complement system , virulence factor , pathogen , polysaccharide , immune system , immunology , gene , biochemistry
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 l actono h ydrolase of C . neoformans , LHC1 in capsular higher order structure. Analysis of extracted capsular polysaccharide from wild-type and lhc1 Δ 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.