Candida albicans Cannot Acquire Sufficient Ethanolamine from the Host To Support Virulence in the Absence of De Novo Phosphatidylethanolamine Synthesis.

Autor:	Davis SE; Department of Microbiology, University of Tennessee, Knoxville, Tennessee, USA., Tams RN; Department of Microbiology, University of Tennessee, Knoxville, Tennessee, USA., Solis NV; Department of Infectious Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA., Wagner AS; Department of Microbiology, University of Tennessee, Knoxville, Tennessee, USA., Chen T; Department of Microbiology, University of Tennessee, Knoxville, Tennessee, USA., Jackson JW; Department of Microbiology, University of Tennessee, Knoxville, Tennessee, USA., Hasim S; Department of Microbiology, University of Tennessee, Knoxville, Tennessee, USA., Montedonico AE; Department of Microbiology, University of Tennessee, Knoxville, Tennessee, USA., Dinsmore J; Department of Microbiology, University of Tennessee, Knoxville, Tennessee, USA., Sparer TE; Department of Microbiology, University of Tennessee, Knoxville, Tennessee, USA., Filler SG; Department of Infectious Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA., Reynolds TB; Department of Microbiology, University of Tennessee, Knoxville, Tennessee, USA treynol6@utk.edu.
Jazyk:	angličtina
Zdroj:	Infection and immunity [Infect Immun] 2018 Jul 23; Vol. 86 (8). Date of Electronic Publication: 2018 Jul 23 (Print Publication: 2018).
DOI:	10.1128/IAI.00815-17
Abstrakt:	Candida albicans mutants for phosphatidylserine (PS) synthase ( cho1 ΔΔ) and PS decarboxylase ( psd1 ΔΔ psd2 ΔΔ) are compromised for virulence in mouse models of systemic infection and oropharyngeal candidiasis (OPC). Both of these enzymes are necessary to synthesize phosphatidylethanolamine (PE) by the de novo pathway, but these mutants are still capable of growth in culture media, as they can import ethanolamine from media to synthesize PE through the Kennedy pathway. Given that the host has ethanolamine in its serum, the exact mechanism by which virulence is lost in these mutants is not clear. There are two competing hypotheses to explain their loss of virulence. (i) PE from the Kennedy pathway cannot substitute for de novo -synthesized PE. (ii) The mutants cannot acquire sufficient ethanolamine from the host to support adequate PE synthesis. These hypotheses can be simultaneously tested if ethanolamine availability is increased for Candida while it is inside the host. We accomplish this by transcomplementation of C. albicans with the Arabidopsis thaliana serine decarboxylase gene ( AtSDC ), which converts cytoplasmic serine to ethanolamine. Expression of AtSDC in either mutant restores PE synthesis, even in the absence of exogenous ethanolamine. AtSDC also restores virulence to cho1 ΔΔ and psd1 ΔΔ psd2 ΔΔ strains in systemic and OPC infections. Thus, in the absence of de novo PE synthesis, C. albicans cannot acquire sufficient ethanolamine from the host to support virulence. In addition, expression of AtSDC restores PS synthesis in the cho1 ΔΔ mutant, which may be due to causing PS decarboxylase to run backwards and convert PE to PS. (Copyright © 2018 American Society for Microbiology.)
Databáze:	MEDLINE
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