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- Title
A Role for <i>LHC1</i> in Higher Order Structure and Complement Binding of the <i>Cryptococcus neoformans</i> Capsule.
- Authors
Park, Yoon-Dong; Shin, Soowan; Panepinto, John; Ramos, Jeanie; Qiu, Jin; Frases, Susana; Albuquerque, Patricia; Cordero, Radames J. B.; Zhang, Nannan; Himmelreich, Uwe; Beenhouwer, David; Bennett, John E.; Casadevall, Arturo; Williamson, Peter R.
- Abstract
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.
- Subjects
CRYPTOCOCCUS neoformans; MICROBIAL polysaccharides; MICROBIAL virulence; COMPLEMENT (Immunology); BACTERIAL capsules
- Publication
PLoS Pathogens, 2014, Vol 10, Issue 5, p1
- ISSN
1553-7366
- Publication type
Article
- DOI
10.1371/journal.ppat.1004037