Role of a CUF1/CTR4 copper regulatory axis in the virulence of Cryptococcus neoformans.

Role of a CUF1/CTR4 copper regulatory axis in the virulence of Cryptococcus neoformans. Research Abstract Details 

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Role of a CUF1/CTR4 copper regulatory axis in the virulence of Cryptococcus neoformans. Abstract Text:

Scott R Waterman,Moshe Hacham,Guowu Hu,Xudong Zhu,Yoon-Dong Park,Soowan Shin,John Panepinto,Tibor Valyi-Nagy,Craig Beam,Shahid Husain,Nina Singh,Peter R Williamson,

The study of regulatory networks in human pathogens such as Cryptococcus neoformans provides insights into host-pathogen interactions that may allow for correlation of gene expression patterns with clinical outcomes. In the present study, deletion of the cryptococcal copper-dependent transcription factor 1 (Cuf1) led to defects in growth and virulence factor expression in low copper conditions. In mouse models, cuf1Delta strains exhibited reduced dissemination to the brain, but no change in lung growth, suggesting copper is limiting in neurologic infections. To examine this further, a biologic probe of available copper was constructed using the cryptococcal CUF1-dependent copper transporter, CTR4. Fungal cells demonstrated high CTR4 expression levels after phagocytosis by macrophage-like J774.16 cells and during infection of mouse brains, but not lungs, consistent with limited copper availability during neurologic infection. This was extended to human brain infections by demonstrating CTR4 expression during C. neoformans infection of an AIDS patient. Moreover, high CTR4 expression by cryptococcal strains from 24 solid organ transplant patients was associated with dissemination to the CNS. Our results suggest that copper acquisition plays a central role in fungal pathogenesis during neurologic infection and that measurement of stable traits such as CTR4 expression may be useful for risk stratification of individuals with cryptococcosis.

Role of a CUF1/CTR4 copper regulatory axis in the virulence of Cryptococcus neoformans. Publishing Authors By Initials

SR Waterman,M Hacham,G Hu,X Zhu,YD Park,S Shin,J Panepinto,T Valyi-Nagy,C Beam,S Husain,N Singh,PR Williamson,

For similar biological phenomena, cell phenomena, and immunity: biological phenomena: microbiologic phenomena: virulence research abstracts see: biological phenomena, cell phenomena, and immunity: biological phenomena: microbiologic phenomena: virulence research

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Role of a CUF1/CTR4 copper regulatory axis in the virulence of Cryptococcus neoformans. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: The Journal of clinical investigation

VOLUME: 117

Page Numbers: 794-802

Journal Abbreviation: J. Clin. Invest.

ISSN: 0021-9738

DAY: 8

MONTH: 02

YEAR: 2007

Role of a CUF1/CTR4 copper regulatory axis in the virulence of Cryptococcus neoformans. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7802877

Role of a CUF1/CTR4 copper regulatory axis in the virulence of Cryptococcus neoformans. Keywords Mesh Terms:

KEYWORDS: Virulence

MESH TERMS: physiology

Chemical & Substance for Abstract: Role of a CUF1/CTR4 copper regulatory axis in the virulence of Cryptococcus neoformans. Information

Substance Name: Copper

Registry Number: 7440-50-8

Grant and Affiliation Information for Role of a CUF1/CTR4 copper regulatory axis in the virulence of Cryptococcus neoformans.

AFFILIATION: Section of Infectious Diseases, Department of Medicine, University of Illinois at Chicago College of Medicine, Chicago, Illinois, USA.

Country: United States

AGENCY: United States NIAID

GRANT: AI49371

ACRONYM: AI

MEDLINETA: J Clin Invest

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