ABSTRACT: Chromosome copy number variation in Cryptococcus neoformans influences virulence and occurs in isolates from AIDS patients: clinal and environmental strains
Project description:This SuperSeries is composed of the following subset Series: GSE29627: Chromosome copy number variation in Cryptococcus neoformans influences virulence and occurs in isolates from AIDS patients: CBS7779 black and white strains GSE29671: Chromosome copy number variation in Cryptococcus neoformans influences virulence and occurs in isolates from AIDS patients: clinal and environmental strains Refer to individual Series
Project description:Chromosome copy number variation in Cryptococcus neoformans influences virulence and occurs in isolates from AIDS patients: CBS7779 black and white strains
Project description:The adaptation of fungal pathogens to the host environment via large-scale genomic changes is a poorly characterized phenomenon. We recently discovered clinical strains of Cryptococcus neoformans, the leading cause of fungal meningoencephalitis in HIV/AIDS patients, which are disomic for chromosome 13. In the current study, we examined the relationship between disomy, expression of the virulence factor melanin and virulence in a mouse model of cryptococcosis. We found that melanin production was correlated with monosomy at chromosome 13, and that disomic variants were less melanized and attenuated for virulence in mice. Changes in the copy number of other chromosomes were also detected in strains showing variation in melanin formation after growth in culture and after passage through mice. A survey of environmental and clinical isolates maintained in culture revealed few occurrences of disomic chromosomes. However, an examination of isolates that were freshly collected from the cerebral spinal fluid of AIDS patients and minimally cultured provided evidence for mixed infections and copy number variation. Overall, these results suggest that the genome of C. neoformans exhibits a greater degree of plasticity than previously appreciated. Importantly, genome variation is associated with virulence factor expression and disease severity, and its occurrence in isolates from AIDS patients suggests that it may have clinical relevance.
Project description:The adaptation of fungal pathogens to the host environment via large-scale genomic changes is a poorly characterized phenomenon. We recently discovered clinical strains of Cryptococcus neoformans, the leading cause of fungal meningoencephalitis in HIV/AIDS patients, which are disomic for chromosome 13. In the current study, we examined the relationship between disomy, expression of the virulence factor melanin and virulence in a mouse model of cryptococcosis. We found that melanin production was correlated with monosomy at chromosome 13, and that disomic variants were less melanized and attenuated for virulence in mice. Changes in the copy number of other chromosomes were also detected in strains showing variation in melanin formation after growth in culture and after passage through mice. A survey of environmental and clinical isolates maintained in culture revealed few occurrences of disomic chromosomes. However, an examination of isolates that were freshly collected from the cerebral spinal fluid of AIDS patients and minimally cultured provided evidence for mixed infections and copy number variation. Overall, these results suggest that the genome of C. neoformans exhibits a greater degree of plasticity than previously appreciated. Importantly, genome variation is associated with virulence factor expression and disease severity, and its occurrence in isolates from AIDS patients suggests that it may have clinical relevance.
Project description:The adaptation of fungal pathogens to the host environment via large-scale genomic changes is a poorly characterized phenomenon. We recently discovered clinical strains of Cryptococcus neoformans, the leading cause of fungal meningoencephalitis in HIV/AIDS patients, which are disomic for chromosome 13. In the current study, we examined the relationship between disomy, expression of the virulence factor melanin and virulence in a mouse model of cryptococcosis. We found that melanin production was correlated with monosomy at chromosome 13, and that disomic variants were less melanized and attenuated for virulence in mice. Changes in the copy number of other chromosomes were also detected in strains showing variation in melanin formation after growth in culture and after passage through mice. A survey of environmental and clinical isolates maintained in culture revealed few occurrences of disomic chromosomes. However, an examination of isolates that were freshly collected from the cerebral spinal fluid of AIDS patients and minimally cultured provided evidence for mixed infections and copy number variation. Overall, these results suggest that the genome of C. neoformans exhibits a greater degree of plasticity than previously appreciated. Importantly, genome variation is associated with virulence factor expression and disease severity, and its occurrence in isolates from AIDS patients suggests that it may have clinical relevance. Genome comparison of clinal and environmental strains vs standard strain H99
Project description:The adaptation of fungal pathogens to the host environment via large-scale genomic changes is a poorly characterized phenomenon. We recently discovered clinical strains of Cryptococcus neoformans, the leading cause of fungal meningoencephalitis in HIV/AIDS patients, which are disomic for chromosome 13. In the current study, we examined the relationship between disomy, expression of the virulence factor melanin and virulence in a mouse model of cryptococcosis. We found that melanin production was correlated with monosomy at chromosome 13, and that disomic variants were less melanized and attenuated for virulence in mice. Changes in the copy number of other chromosomes were also detected in strains showing variation in melanin formation after growth in culture and after passage through mice. A survey of environmental and clinical isolates maintained in culture revealed few occurrences of disomic chromosomes. However, an examination of isolates that were freshly collected from the cerebral spinal fluid of AIDS patients and minimally cultured provided evidence for mixed infections and copy number variation. Overall, these results suggest that the genome of C. neoformans exhibits a greater degree of plasticity than previously appreciated. Importantly, genome variation is associated with virulence factor expression and disease severity, and its occurrence in isolates from AIDS patients suggests that it may have clinical relevance. Genome comparison of CBS7779 black and white strains vs standard strain H99
Project description:Influence of copy number changes at several chromosomes to melanin production and virulence of Cryptococcus neoformans Black(B4) and white(W2) strains were compared to each other. Black variant from white strain (W2BA1) is also compared to the black strain(B4).
