Convergent microevolution of Cryptococcus neoformans hypervirulence in the laboratory and the clinic

Samantha D.M. Arras, Kate L. Ormerod, Paige E. Erpf, Monica I. Espinosa, Alex C. Carpenter, Ross D. Blundell, Samantha R. Stowasser, Benjamin L. Schulz, Milos Tanurdzic, James A. Fraser

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Reference strains are a key component of laboratory research, providing a common background allowing for comparisons across a community of researchers. However, laboratory passage of these strains has been shown to lead to reduced fitness and the attenuation of virulence in some species. In this study we show the opposite in the fungal pathogen Cryptococcus neoformans, with analysis of a collection of type strain H99 subcultures revealing that the most commonly used laboratory subcultures belong to a mutant lineage of the type strain that is hypervirulent. The pleiotropic mutant phenotypes in this H99L (for "Laboratory") lineage are the result of a deletion in the gene encoding the SAGA Associated Factor Sgf29, a mutation that is also present in the widely-used H99L-derived KN99a/α congenic pair. At a molecular level, loss of this gene results in a reduction in histone H3K9 acetylation. Remarkably, analysis of clinical isolates identified loss of function SGF29 mutations in C. neoformans strains infecting two of fourteen patients, demonstrating not only the first example of hypervirulence in clinical C. neoformans samples, but also parallels between in vitro and in vivo microevolution for hypervirulence in this important pathogen.

LanguageEnglish
Article number17918
Pages1-14
Number of pages14
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - 20 Dec 2017
Externally publishedYes

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Cryptococcus neoformans
Mutation
Gene Deletion
Acetylation
Histones
Virulence
Research Personnel
Phenotype
Research
Genes

Bibliographical note

Copyright the Author(s) 2017. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Cite this

Arras, S. D. M., Ormerod, K. L., Erpf, P. E., Espinosa, M. I., Carpenter, A. C., Blundell, R. D., ... Fraser, J. A. (2017). Convergent microevolution of Cryptococcus neoformans hypervirulence in the laboratory and the clinic. Scientific Reports, 7(1), 1-14. [17918]. https://doi.org/10.1038/s41598-017-18106-2
Arras, Samantha D.M. ; Ormerod, Kate L. ; Erpf, Paige E. ; Espinosa, Monica I. ; Carpenter, Alex C. ; Blundell, Ross D. ; Stowasser, Samantha R. ; Schulz, Benjamin L. ; Tanurdzic, Milos ; Fraser, James A. / Convergent microevolution of Cryptococcus neoformans hypervirulence in the laboratory and the clinic. In: Scientific Reports. 2017 ; Vol. 7, No. 1. pp. 1-14.
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Arras, SDM, Ormerod, KL, Erpf, PE, Espinosa, MI, Carpenter, AC, Blundell, RD, Stowasser, SR, Schulz, BL, Tanurdzic, M & Fraser, JA 2017, 'Convergent microevolution of Cryptococcus neoformans hypervirulence in the laboratory and the clinic', Scientific Reports, vol. 7, no. 1, 17918, pp. 1-14. https://doi.org/10.1038/s41598-017-18106-2

Convergent microevolution of Cryptococcus neoformans hypervirulence in the laboratory and the clinic. / Arras, Samantha D.M.; Ormerod, Kate L.; Erpf, Paige E.; Espinosa, Monica I.; Carpenter, Alex C.; Blundell, Ross D.; Stowasser, Samantha R.; Schulz, Benjamin L.; Tanurdzic, Milos; Fraser, James A.

In: Scientific Reports, Vol. 7, No. 1, 17918, 20.12.2017, p. 1-14.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Carpenter, Alex C.

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AU - Stowasser, Samantha R.

AU - Schulz, Benjamin L.

AU - Tanurdzic, Milos

AU - Fraser, James A.

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N2 - Reference strains are a key component of laboratory research, providing a common background allowing for comparisons across a community of researchers. However, laboratory passage of these strains has been shown to lead to reduced fitness and the attenuation of virulence in some species. In this study we show the opposite in the fungal pathogen Cryptococcus neoformans, with analysis of a collection of type strain H99 subcultures revealing that the most commonly used laboratory subcultures belong to a mutant lineage of the type strain that is hypervirulent. The pleiotropic mutant phenotypes in this H99L (for "Laboratory") lineage are the result of a deletion in the gene encoding the SAGA Associated Factor Sgf29, a mutation that is also present in the widely-used H99L-derived KN99a/α congenic pair. At a molecular level, loss of this gene results in a reduction in histone H3K9 acetylation. Remarkably, analysis of clinical isolates identified loss of function SGF29 mutations in C. neoformans strains infecting two of fourteen patients, demonstrating not only the first example of hypervirulence in clinical C. neoformans samples, but also parallels between in vitro and in vivo microevolution for hypervirulence in this important pathogen.

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