Phenotypic switching in the human pathogenic fungusCryptococcus neoformansis associated with changes in virulence and pulmonary inflammatory response in rodents

Abstract

High-frequency reversible changes in colony morphology were observed in three strains of Cryptococcus neoformans. For one strain (SB4, serotype A), this process produced three colony types: smooth (S), wrinkled (W), and serrated (C). The frequency of switching between colony types varied for the individual colony transitions and was as high as 10 ؊3 . Mice infected with colony type W died faster than those infected with other colony types. The rat inf lammatory response to infection with colony types S, W, and C was C > S > W and ranged from intense granulomatous inf lammation with caseous necrosis for infection with type C to minimal inf lammation for infection with type W. Infection with the various colony types was associated with different antibody responses to cryptococcal proteins in rats. Analysis of cellular characteristics revealed differences between the three colony types. High-frequency changes in colony morphology were also observed in two additional strains of C. neoformans. For one strain (24067A, serotype D) the switching occurred between smooth and wrinkled colonies. For the other strain (J32A, serotype A), the switching occurred between mucoid and nonmucoid colonies. The findings indicate that C. neoformans undergoes phenotypic switching and that this process can affect virulence and host inf lammatory and immune responses. Phenotypic switching may play a role in the ability of this fungus to escape host defenses and establish chronic infections.

Increased release of glucuronoxylomannan antigen and induced phenotypic changes in Trichosporon asahii by repeated passage in mice

“…This process is thought to allow some fungi to escape eradication by the host immune system [11,[13][14][15]. However, to our knowledge, there are no studies that have previously examined phenotypic changes within the genus Trichosporon after passages in vivo.…”

“…neoformans change their phenotypes when they are subcultured repeatedly or passaged in vivo [11][12][13][14][15][16]. C. albicans spontaneously switches the morphology of its colonies into at least seven general phenotypes [16].…”

“…In this regard, clinically important fungi such as Candida albicans and Cryptococcus neoformans are known to change their phenotype after repeated subcultures or in-vivo passages [11][12][13][14][15][16]. This process is thought to allow some fungi to escape eradication by the host immune system [11,[13][14][15].…”

Phenotypic Switching of Cryptococcus neoformans and Cryptococcus gattii

“…Phenotypic switching is defined as the emergence of reversible colony morphology at a rate higher than somatic mutation rate. Reversible switching between various colony morphologies (smooth, wrinkled, mucoid, and pseudohyphal) has been observed in standard strains (SB4, J32, RC2) of serotypes A and D [28,29]. This colony-type switching is associated with changes in virulence and in host inflammatory and antibody responses in murine and rat model.…”

“…In addition the phenotypes are very stable and thus this strain has been a model strain to investigate phenotypic switching. However, other switching strains are described and include serotypes A and other D strains and hence highlight the notion that phenotypic switching is a general phenomenon [28,29].…”