SORA

Advancing, promoting and sharing knowledge of health through excellence in teaching, clinical practice and research into the prevention and treatment of illness

Variation in chromosome copy number influences the virulence of Cryptococcus neoformans and occurs in isolates from AIDS patients.

Hu, G; Wang, J; Choi, J; Jung, WH; Liu, I; Litvintseva, AP; Bicanic, T; Aurora, R; Mitchell, TG; Perfect, JR; et al. Hu, G; Wang, J; Choi, J; Jung, WH; Liu, I; Litvintseva, AP; Bicanic, T; Aurora, R; Mitchell, TG; Perfect, JR; Kronstad, JW (2011) Variation in chromosome copy number influences the virulence of Cryptococcus neoformans and occurs in isolates from AIDS patients. BMC GENOMICS, 12 (526). ISSN 1471-2164 https://doi.org/10.1186/1471-2164-12-526
SGUL Authors: Bicanic, Tihana

[img]
Preview
PDF Published Version
Download (403kB) | Preview

Abstract

BACKGROUND: The adaptation of pathogenic fungi to the host environment via large-scale genomic changes is a poorly characterized phenomenon. Cryptococcus neoformans is the leading cause of fungal meningoencephalitis in HIV/AIDS patients, and we recently discovered clinical strains of the fungus that are disomic for chromosome 13. Here, we examined the genome plasticity and phenotypes of monosomic and disomic strains, and compared their virulence in a mouse model of cryptococcosis RESULTS: In an initial set of strains, melanin production was correlated with monosomy at chromosome 13, and disomic variants were less melanized and attenuated for virulence in mice. After growth in culture or passage through mice, subsequent strains were identified that varied in melanin formation and exhibited copy number changes for other chromosomes. The correlation between melanin and disomy at chromosome 13 was observed for some but not all strains. 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 cerebrospinal fluid of AIDS patients and minimally cultured provided evidence for infections with multiple strains and copy number variation. CONCLUSIONS: Overall, these results suggest that the genome of C. neoformans exhibits a greater degree of plasticity than previously appreciated. Furthermore, the expression of an essential virulence factor and the severity of disease are associated with genome variation. The occurrence of chromosomal variation in isolates from AIDS patients, combined with the observed influence of disomy on virulence, indicates that genome plasticity may have clinical relevance.

Item Type: Article
Additional Information: PubMed ID: 22032296 © 2011 Hu et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: AIDS-Related Opportunistic Infections, Animals, Chromosomes, Fungal, Comparative Genomic Hybridization, Cryptococcosis, Cryptococcus neoformans, DNA Copy Number Variations, Female, Humans, Melanins, Mice, Mice, Inbred BALB C, Virulence, Virulence Factors, Comparative genome hybridization, fungal pathogenesis, meningitis, Science & Technology, Life Sciences & Biomedicine, Biotechnology & Applied Microbiology, Genetics & Heredity, Comparative genome hybridization, fungal pathogenesis, meningitis, VAR. GRUBII SEROTYPE, CANDIDA-ALBICANS, MATING-TYPE, WIDESPREAD ANEUPLOIDY, ANTIGENIC VARIATION, YEAST, EVOLUTION, MENINGITIS, INFECTION, STRAINS
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: BMC GENOMICS
ISSN: 1471-2164
Related URLs:
Dates:
DateEvent
27 October 2011Published
Web of Science ID: WOS:000297222600001
Download EPMC Full text (PDF)
Download EPMC Full text (HTML)
URI: http://openaccess.sgul.ac.uk/id/eprint/15
Publisher's version: https://doi.org/10.1186/1471-2164-12-526

Actions (login required)

Edit Item Edit Item