Journal
INFECTION AND IMMUNITY
Volume 79, Issue 12, Pages 4990-5000Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/IAI.05789-11
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Categories
Funding
- NIH [AI033774, HL059842, AI033142]
- Training Program in Cellular and Molecular Biology and Genetics [T32 GM007491]
- National Institutes of Health (NIH) [AI-51519]
- Conselho Nacional de Desenvolvimento Tecnologico (CNPq)
- Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ)
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
- Instituto Nacional de Ciencia e Tecnologia de Fluidos Complexos (INCT-FCx)
- FAPESP
- FINEP
- Long Island University
- C.W. Post Campus, Faculty Research Committee
- Department of Energy Center for Plant and Microbial Complex Carbohydrates [DE-FG-9-93ER-20097]
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Does the age of a microbial cell affect its virulence factors? To our knowledge, this question has not been addressed previously, but the answer is of great relevance for chronic infections where microbial cells persist and age in hosts. Cryptococcus neoformans is an encapsulated human-pathogenic fungus notorious for causing chronic infections where cells of variable age persist in tissue. The major virulence factor for C. neoformans is a polysaccharide (PS) capsule. To understand how chronological age could impact the cryptococcal capsule properties, we compared the elastic properties, permeabilities, zeta potentials, and glycosidic compositions of capsules from young and old cells and found significant differences in all parameters measured. Changes in capsular properties were paralleled by changes in PS molecular mass and density, as well as modified antigenic density and antiphagocytic properties. Remarkably, chronological aging under stationary-phase growth conditions was associated with the expression of alpha-1,3-glucans in the capsule, indicating a new structural capsular component. Our results establish that cryptococcal capsules are highly dynamic structures that change dramatically with chronological aging under prolonged stationary-phase growth conditions. Changes associated with cellular aging in chronic infections could contribute to the remarkable capacity of this fungus to persist in tissues by generating phenotypically and antigenically different capsules.
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