Dark brown is the more virulent of the switch phenotypes of Candida glabrata

Abstract

Candida glabrata undergoes reversible, high-frequency core switching between phenotypes that include dark brown (DB), light brown (LB) and white (Wh). These phenotypes in turn can switch to the irregular wrinkle (IWr) phenotype. Natural isolates, however, express predominantly the DB phenotype, leading to the hypothesis that it has a colonization advantage over the other switch phenotypes. Using the mouse model of systemic infection, results are presented which support this hypothesis. DB has an advantage over other switch phenotypes in colonizing the two major target organs in the mouse model, the spleen and liver. A time-course study reveals that colonization of the major target organs occurs very rapidly (within 2 h) after host injection, and that the DB advantage for spleen and liver colonization is immediate. The DB advantage is maintained during clearing from spleen, liver and kidneys, and during delayed transient brain colonization. These results demonstrate that DB has a colonization advantage over other switch phenotypes, and that the switch phenotype expressed by a colonizing population therefore plays a fundamental role in virulence. It is therefore essential that switching be considered in both in vivo and in vitro studies of C. glabrata virulence.

Human Colors—The Rainbow Garden of Pathology: What Gives Normal and Pathologic Tissues Their Color?

“…32,33 Interestingly, melanin pigments produced by fungi (dematiaceous fungi, Cryptococcus spp, Aspergillus spp, Candida spp, Penicillium spp, among others) have a role in the survival and virulence of these organisms by interfering with the host immune phagocytic mechanisms ( Figure 5, I). 5,34,35 Eumelanin is also the main component of the ink produced by coleoid cephalopods, that is squids (Teuthida), cuttlefish (Sepiida), and octopuses (Octopoda). Eumelanin is stored in an ink sac and released in several patterns (pseudomorphs, ink ropes, clouds, smokescreens, among others) and functions as a distractor to escape predation.…”

Candida glabrata Persistence in Mice Does Not Depend on Host Immunosuppression and Is Unaffected by Fungal Amino Acid Auxotrophy

“…In the absence of mortality, the fungal burden has been used as a parameter for virulence and the efficacy of antifungal treatment for cyclophosphamide-treated mice (4,41). Similarly, fungal burdens have been determined for immunocompetent mice systemically infected with C. glabrata (6,16,43); however, differences in mouse strains, animal age and gender, the C. glabrata strain used, and infectious doses hamper direct comparison of published data from immunocompetent and immunosuppressed mice. Thus, the influence of immunosuppression on systemic C. glabrata infections in mice is still unclear.…”

Aneuploidy underlies a multicellular phenotypic switch

“…C. albicans can also differentiate a subpopulation of "persister" cells that, like their bacterial counterparts, exhibit increased resistance to antimicrobial drugs (15). Candida glabrata exhibits at least two spontaneous and reversible phenotypic switches: a "core switching system" and an "irregular wrinkle switching system" (16) which exhibit differential tissue colonization and clearing rates in vivo (17). Cryptococcus neoformans switches between smooth, mucoid, pseudohyphal, and wrinkled colonies: state changes that are associated with biochemically distinct capsular polysaccharides (18), changes in karyotype (18), and differential fungal burden in infected host organs (19).…”