Chronological Aging Is Associated with Biophysical and Chemical Changes in the Capsule of Cryptococcus neoformans

Abstract

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 ␣-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.

Chitin-Like Molecules Associate with Cryptococcus neoformans Glucuronoxylomannan To Form a Glycan Complex with Previously Unknown Properties

“…The attributes of the capsular components have classically been examined with isolated polysaccharide fractions (9), although a number of studies strongly suggest that these molecules are associated to other components of the cell surface of C. neoformans (14,17,20,21,28,35,(39)(40)(41). Our results suggest that chitin-derived structures associate with GXM through their N-acetyl amino groups generating complex glycans with previously unknown functions.…”

“…Carbohydrate-carbohydrate interactions are presumably required for capsule organization and, in fact, GXM interacts with other polysaccharide molecules at the cell surface (46). Self-aggregation (GXM-GXM interactions) is required for capsule enlargement (24,35), but the polysaccharide is also likely to interact with cell wall glucans, which are essential for capsule anchoring and cell wall architecture (14,25,39,40). Microscopic examination revealed that GXM is also associated with GXMGal at the capsular network (17).…”

Elucidating the Immunological Function of the Cryptococcus Neoformans Capsule

“…The role of MPs in the virulence of C. neoformans and in the structure of capsule is not fully elucidated. Moreover, cryptococcal capsules are considered highly dynamic structures [55]. Several antigenic capsule changes, associated with cellular aging and generated during chronic infection, could reflect the remarkable capacity of this fungus to escape the immune response and persist in tissues.…”

Macrophage–Cryptococcus Interactions: An Update

“…A comparison of the biophysical and chemical profiles of the capsule between younger and older generations showed uniquely distinct carbohydrate moieties. C. neoformans isolates from later generations demonstrate enhanced anti-phagocytic properties suggesting that Cryptococcal capsules have a unique plasticity that allow adaptation to the host environment for prolonged survival (37). The precise intracellular cues that govern cryptococcal microevolution through altering capsular carbohydrate composition require further investigation.…”