A role for LHC1 in higher order structure and complement binding of the Cryptococcus neoformans capsule.

• Main Authors: Yoon-Dong Park, Soowan Shin, John Panepinto, Jeanie Ramos, Jin Qiu, Susana Frases, Patricia Albuquerque, Radames J B Cordero, Nannan Zhang, Uwe Himmelreich, David Beenhouwer, John E Bennett, Arturo Casadevall, Peter R Williamson
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2014-05-01
• Series: PLoS Pathogens
• Online Access: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24789368/?tool=EBI

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.