Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Hu, Guanggan, Wang, Joyce, Choi, Jaehyuk, Jung, Won Hee, Liu, Iris, Litvintseva, Anastasia P, Bicanic, Tihana, Aurora, Rajeev, Mitchell, Thomas G, Perfect, John R, Kronstad, James W
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3221739/
https://www.ncbi.nlm.nih.gov/pubmed/22032296
http://dx.doi.org/10.1186/1471-2164-12-526
_version_ 1782217131720441856
author Hu, Guanggan
Wang, Joyce
Choi, Jaehyuk
Jung, Won Hee
Liu, Iris
Litvintseva, Anastasia P
Bicanic, Tihana
Aurora, Rajeev
Mitchell, Thomas G
Perfect, John R
Kronstad, James W
author_facet Hu, Guanggan
Wang, Joyce
Choi, Jaehyuk
Jung, Won Hee
Liu, Iris
Litvintseva, Anastasia P
Bicanic, Tihana
Aurora, Rajeev
Mitchell, Thomas G
Perfect, John R
Kronstad, James W
author_sort Hu, Guanggan
collection PubMed
description 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.
format Online
Article
Text
id pubmed-3221739
institution National Center for Biotechnology Information
language English
publishDate 2011
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-32217392011-11-22 Variation in chromosome copy number influences the virulence of Cryptococcus neoformans and occurs in isolates from AIDS patients Hu, Guanggan Wang, Joyce Choi, Jaehyuk Jung, Won Hee Liu, Iris Litvintseva, Anastasia P Bicanic, Tihana Aurora, Rajeev Mitchell, Thomas G Perfect, John R Kronstad, James W BMC Genomics Research Article 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. BioMed Central 2011-10-27 /pmc/articles/PMC3221739/ /pubmed/22032296 http://dx.doi.org/10.1186/1471-2164-12-526 Text en Copyright ©2011 Hu et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 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.
spellingShingle Research Article
Hu, Guanggan
Wang, Joyce
Choi, Jaehyuk
Jung, Won Hee
Liu, Iris
Litvintseva, Anastasia P
Bicanic, Tihana
Aurora, Rajeev
Mitchell, Thomas G
Perfect, John R
Kronstad, James W
Variation in chromosome copy number influences the virulence of Cryptococcus neoformans and occurs in isolates from AIDS patients
title Variation in chromosome copy number influences the virulence of Cryptococcus neoformans and occurs in isolates from AIDS patients
title_full Variation in chromosome copy number influences the virulence of Cryptococcus neoformans and occurs in isolates from AIDS patients
title_fullStr Variation in chromosome copy number influences the virulence of Cryptococcus neoformans and occurs in isolates from AIDS patients
title_full_unstemmed Variation in chromosome copy number influences the virulence of Cryptococcus neoformans and occurs in isolates from AIDS patients
title_short Variation in chromosome copy number influences the virulence of Cryptococcus neoformans and occurs in isolates from AIDS patients
title_sort variation in chromosome copy number influences the virulence of cryptococcus neoformans and occurs in isolates from aids patients
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3221739/
https://www.ncbi.nlm.nih.gov/pubmed/22032296
http://dx.doi.org/10.1186/1471-2164-12-526
work_keys_str_mv AT huguanggan variationinchromosomecopynumberinfluencesthevirulenceofcryptococcusneoformansandoccursinisolatesfromaidspatients
AT wangjoyce variationinchromosomecopynumberinfluencesthevirulenceofcryptococcusneoformansandoccursinisolatesfromaidspatients
AT choijaehyuk variationinchromosomecopynumberinfluencesthevirulenceofcryptococcusneoformansandoccursinisolatesfromaidspatients
AT jungwonhee variationinchromosomecopynumberinfluencesthevirulenceofcryptococcusneoformansandoccursinisolatesfromaidspatients
AT liuiris variationinchromosomecopynumberinfluencesthevirulenceofcryptococcusneoformansandoccursinisolatesfromaidspatients
AT litvintsevaanastasiap variationinchromosomecopynumberinfluencesthevirulenceofcryptococcusneoformansandoccursinisolatesfromaidspatients
AT bicanictihana variationinchromosomecopynumberinfluencesthevirulenceofcryptococcusneoformansandoccursinisolatesfromaidspatients
AT aurorarajeev variationinchromosomecopynumberinfluencesthevirulenceofcryptococcusneoformansandoccursinisolatesfromaidspatients
AT mitchellthomasg variationinchromosomecopynumberinfluencesthevirulenceofcryptococcusneoformansandoccursinisolatesfromaidspatients
AT perfectjohnr variationinchromosomecopynumberinfluencesthevirulenceofcryptococcusneoformansandoccursinisolatesfromaidspatients
AT kronstadjamesw variationinchromosomecopynumberinfluencesthevirulenceofcryptococcusneoformansandoccursinisolatesfromaidspatients