Lausannevirus Encodes a Functional Dihydrofolate Reductase Susceptible to Proguanil.

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Ressource 1Download: Antimicrob. Agents Chemother.-2017-Mueller-.pdf (1610.48 [Ko])
State: Public
Version: Final published version
Serval ID
serval:BIB_6E1D5B0AB128
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Lausannevirus Encodes a Functional Dihydrofolate Reductase Susceptible to Proguanil.
Journal
Antimicrobial agents and chemotherapy
Author(s)
Mueller L., Hauser P.M., Gauye F., Greub G.
ISSN
1098-6596 (Electronic)
ISSN-L
0066-4804
Publication state
Published
Issued date
04/2017
Peer-reviewed
Oui
Volume
61
Number
4
Pages
e02573-16
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Lausannevirus belongs to the family Marseilleviridae within the group of nucleocytoplasmic large DNA viruses (NCLDVs). These giant viruses exhibit unique features, including a large genome, ranging from 100 kb to 2.5 Mb and including from 150 to more than 2,500 genes, as well as the presence of genes coding for proteins involved in transcription and translation. The large majority of Lausannevirus open reading frames have unknown functions. Interestingly, a bifunctional dihydrofolate reductase-thymidylate synthase (DHFR-TS) is encoded in the Lausannevirus genome. The enzyme plays central roles in DNA precursor biosynthesis. DHFR is the pharmacological target of antifolates, such as trimethoprim, pyrimethamine, and proguanil. First, the functionality of Lausannevirus DHFR-TS was demonstrated by the successful complementation of a DHFR-deficient Saccharomyces cerevisiae strain with a plasmid expressing the heterologous gene. Additionally, using this heterologous expression system, we demonstrated the in vitro susceptibility of Lausannevirus DHFR-TS to proguanil and its resistance to pyrimethamine and trimethoprim. Proguanil may provide a unique and useful treatment if Lausannevirus proves to be a human pathogen. To our knowledge, this is the first time that a DHFR-TS has been described and characterized in an NCLDV.

Pubmed
Web of science
Open Access
Yes
Create date
07/02/2017 18:16
Last modification date
20/08/2019 14:27
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