Abstract
The Cryptococcus neoformans species complex (CNSC) is a common opportunistic human fungal pathogen and the most frequent cause of fungal meningitis. There are three major serotypes in CNSC: A, D, and their hybrids AD, and they have different geographic distributions and medical significance. Melanin pigment and a polysaccharide capsule are the two major virulence factors in CNSC. However, the relationships between serotype and virulence factor production and how environmental factors might impact their relationships are not known. This study investigated the expressions of melanin and capsular polysaccharide in a genetically diverse group of CNSC strains and how their phenotypic expressions were influenced by oxidative and nitrosative stress levels. We found significant differences in melanin and capsular polysaccharide productions among serotypes and across stress conditions. Under oxidative stress, the laboratory hybrids exhibited the highest phenotypic plasticity for melanin production while serotype A showed the highest for capsular polysaccharide production. In contrast, serotype D exhibited the highest phenotypic plasticity for capsular polysaccharide production and clinical serotype AD the highest phenotypic plasticity for melanin production under nitrosative stress. These results demonstrated that different serotypes have different environmental condition-specific mechanisms to modulate the expression of virulence factors.
Highlights
Cryptococcus neoformans species complex (CNSC) is a major human fungal pathogen that causes hundreds of thousands of deaths each year [1, 2]
Different environmental stressor levels showed differential contributions to the variances associated with melanin production, and there were significant interaction effects between environmental conditions with CNSC strains and serotypes (Fig. 1C)
Our study indicates that both melanin and capsular polysaccharide productions in CNSC are significantly influenced by serotypes, strains, environmental stressors, and interactions among these factors
Summary
Cryptococcus neoformans species complex (CNSC) is a major human fungal pathogen that causes hundreds of thousands of deaths each year [1, 2]. The CNSC is comprised of two main evolutionary divergent lineages that have been variably called serotypes (A and D), genotype groups (VNI, VNII, VNB, and VNIV), varieties Neoformans), and species (C. neoformans and C. deneoformans). The strains of serotype A correspond to genotype groups VNI, VNII, VNB; variety grubii; and species C. neoformans. The strains of serotype D correspond to genotype group VNIV; var. Within CNSC, serotype AD hybrids (genotype group VNIII) are commonly found in certain geographic regions [1]. We will use the term serotype to refer to the genetically divergent groups of strains within CNSC. The reason(s) for the high prevalence of serotype A strains in patients remains largely unknown
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