title: Antibody binding to Cryptococcus neoformans impairs budding by altering capsular mechanical properties.
abstract: Abs to microbial capsules are critical for host defense against encapsulated pathogens, but very little is known about the effects of Ab binding on the capsule, apart from producing qualitative capsular reactions ("quellung" effects). A problem in studying Ab-capsule interactions is the lack of experimental methodology, given that capsules are fragile, highly hydrated structures. In this study, we pioneered the use of optical tweezers microscopy to study Ab-capsule interactions. Binding of protective mAbs to the capsule of the fungal pathogen Cryptococcus neoformans impaired yeast budding by trapping newly emerging buds inside the parental capsule. This effect is due to profound mAb-mediated changes in capsular mechanical properties, demonstrated by a concentration-dependent increase in capsule stiffness. This increase involved mAb-mediated cross-linking of capsular polysaccharide molecules. These results provide new insights into Ab-mediated immunity, while suggesting a new nonclassical mechanism of Ab function, which may apply to other encapsulated pathogens. Our findings add to the growing body of evidence that Abs have direct antimicrobial functions independent of other components of the immune system.
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Radames J B
authors.initials: RJ
authors.lastname: Cordero
authors.forename: Bruno
authors.initials: B
authors.lastname: Pontes
authors.forename: Susana
authors.initials: S
authors.lastname: Frases
authors.forename: Antonio S
authors.initials: AS
authors.lastname: Nakouzi
authors.forename: Leonardo
authors.initials: L
authors.lastname: Nimrichter
authors.forename: Marcio L
authors.initials: ML
authors.lastname: Rodrigues
authors.forename: Nathan B
authors.initials: NB
authors.lastname: Viana
authors.forename: Arturo
authors.initials: A
authors.lastname: Casadevall
mesh_terms: D000908:Antibodies, Fungal / Q000009:adverse effects / Q000378:metabolism* / Q000502:physiology; D000946:Antigens, Fungal / Q000276:immunology; D001666:Binding Sites, Antibody; D002455:Cell Division / Q000276:immunology; D003453:Cryptococcosis / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D003455:Cryptococcus neoformans / Q000166:cytology / Q000254:growth & development* / Q000276:immunology*; D062607:Fungal Capsules / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D057446:Hydrodynamics; D052898:Optical Tweezers; D011134:Polysaccharides / Q000276:immunology* / Q000378:metabolism; D013314:Stress, Mechanical
chemical_list: D000908:Antibodies, Fungal; D000946:Antigens, Fungal; D011134:Polysaccharides; C027478:glucuronoxylomannan