The interplay of phenotype and genotype inCryptococcus neoformansdisease

Abstract

Cryptococcus neoformans is an opportunistic fungal pathogen that causes life-threatening meningitis primarily in immunocompromised individuals. In order to survive and proliferate during infection, C. neoformans must adapt to a variety of stresses it encounters within the host. Patient outcome depends on the interaction between the pathogen and the host. Understanding the mechanisms that C. neoformans uses to facilitate adaptation to the host and promote pathogenesis is necessary to better predict disease severity and establish proper treatment. Several virulence phenotypes have been characterized in C. neoformans, but the field still lacks a complete understanding of how genotype and phenotype contribute to clinical outcome. Furthermore, while it is known that C. neoformans genotype impacts patient outcome, the mechanisms remain unknown. This lack of understanding may be due to the genetic heterogeneity of C. neoformans and the extensive phenotypic variation observed between and within isolates during infection. In this review, we summarize the current understanding of how the various genotypes and phenotypes observed in C. neoformans correlate with human disease progression in the context of patient outcome and recurrence. We also postulate the mechanisms underlying the genetic and phenotypic changes that occur in vivo to promote rapid adaptation in the host.

The Cyclin Cln1 Controls Polyploid Titan Cell Formation following a Stress-Induced G 2 Arrest in Cryptococcus

“…3B ). In addition to their large size, titan cells are defined by their increased ploidy and the high chitin content in their cell wall ( 36 – 38 ). The large cln1Δ cells isolated from mice had higher levels of both DNA and chitin, indicating the cln1Δ cells are bona fide titan cells ( Fig.…”

Associations between Cryptococcus Genotypes, Phenotypes, and Clinical Parameters of Human Disease: A Review

“…C. neoformans more efficiently disseminates to the CNS and thereby more frequently causes CM. However, C. gattii primarily causes PC while C. neoformans and C. deneoformans primarily cause CM and C. deneoformans most often causes skin lesions [ 100 ]. Cryptococcal strains are generally either MATa or MATα.…”

The cyclin Cln1 controls polyploid titan cell formation following a stress-induced G2 arrest in Cryptococcus

“…The cln1∆ cells had a significant increase in cell body diameter compared to the wild type cells, while the overexpression strains had cell body sizes smaller than the wild type cells (Figure 3B). In addition to their large size, titan cells are defined by their increased ploidy and the high chitin content in their cell wall (36)(37)(38). The large cln1∆ cells isolated from mice had higher levels of both DNA and chitin, indicating the cln1Δ cells are bona fide titan cells (Figure 3C and 3D).…”