Molecular genetic analysis of purine nucleobase transport in Leishmania major.

Molecular genetic analysis of purine nucleobase transport in Leishmania major. Research Abstract Details 

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Molecular genetic analysis of purine nucleobase transport in Leishmania major. Abstract Text:

Diana Ortiz,Marco A Sanchez,Steven Pierce,Timo Herrmann,Nicola Kimblin,H G Archie Bouwer,Scott M Landfear,

Leishmania major and all other parasitic protozoa are unable to synthesize purines de novo and are therefore reliant upon uptake of preformed purines from their hosts via nucleobase and nucleoside transporters. L. major expresses two nucleobase permeases, NT3 that is a high affinity transporter for purine nucleobases and NT4 that is a low affinity transporter for adenine. nt3((-/-)) null mutant promastigotes were unable to replicate in medium containing 10 microM hypoxanthine, guanine, or xanthine and replicated slowly in 10 microM adenine due to residual low affinity uptake of that purine. The NT3 transporter mediated the uptake of the anti-leishmanial drug allopurinol, and the nt3((-/-)) mutants were resistant to killing by this drug. Expression of the NT3 permease was profoundly downregulated at the protein but not the mRNA level in stationary phase compared with logarithmic phase promastigotes. The nt4((-/-)) null mutant was quantitatively impaired in survival within murine bone marrow-derived macrophages. Extensive efforts to generate an nt3((-/-))/nt4((-/-)) dual null mutant were not successful, suggesting that one of the two nucleobase permeases must be retained for robust growth of the parasite. The phenotypes of these null mutants underscore the importance of purine nucleobase transporters in the Leishmania life cycle and pharmacology.

Molecular genetic analysis of purine nucleobase transport in Leishmania major. Publishing Authors By Initials

D Ortiz,MA Sanchez,S Pierce,T Herrmann,N Kimblin,HG Archie Bouwer,SM Landfear,

For similar heterocyclic compounds: heterocyclic compounds, 2-ring: purines research abstracts see: heterocyclic compounds: heterocyclic compounds, 2-ring: purines research

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Molecular genetic analysis of purine nucleobase transport in Leishmania major. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Molecular microbiology

VOLUME: 64

Page Numbers: 1228-43

Journal Abbreviation: Mol. Microbiol.

ISSN: 0950-382X

DAY: 3

MONTH: Jun

YEAR: 2007

Molecular genetic analysis of purine nucleobase transport in Leishmania major. Information

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LANGUAGE: eng

NlmUniqueID: 8712028

Molecular genetic analysis of purine nucleobase transport in Leishmania major. Keywords Mesh Terms:

KEYWORDS: Purines

MESH TERMS: metabolism

Chemical & Substance for Abstract: Molecular genetic analysis of purine nucleobase transport in Leishmania major. Information

Substance Name: Green Fluorescent Proteins

Registry Number: 147336-22-9

Grant and Affiliation Information for Molecular genetic analysis of purine nucleobase transport in Leishmania major.

AFFILIATION: Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR 97239, USA.

Country: England

AGENCY: United States NIAID

GRANT: AI44138

ACRONYM: AI

MEDLINETA: Mol Microbiol

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