Candida albicans Cannot Acquire Sufficient Ethanolamine from the Host To Support Virulence in the Absence of De Novo Phosphatidylethanolamine Synthesis
| Autor: | Sarah E. Davis, Scott G. Filler, Tim E. Sparer, Anthony E. Montedonico, Robert N. Tams, Tian Chen, Sahar Hasim, Joseph W. Jackson, Justin T. Dinsmore, Norma V. Solis, Andrew S. Wagner, Todd B. Reynolds |
|---|---|
| Přispěvatelé: | Deepe, George S |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
phosphatidylserine mice Carboxy-Lyases 030106 microbiology Immunology Mutant Virulence Biology Medical and Health Sciences Microbiology Serine Mice 03 medical and health sciences chemistry.chemical_compound Ethanolamine Sepsis Candida albicans Animals 2.2 Factors relating to the physical environment 2.1 Biological and endogenous factors oropharyngeal Aetiology Phosphatidylethanolamine Agricultural and Veterinary Sciences Phosphatidylethanolamines Genetic Variation Hematology Biological Sciences biology.organism_classification Corpus albicans De novo synthesis 030104 developmental biology Infectious Diseases chemistry phosphatidylethanolamine Host-Pathogen Interactions Parasitology Fungal and Parasitic Infections serine decarboxylase |
| Zdroj: | Infection and immunity, vol 86, iss 8 |
| ISSN: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.00815-17 |
| Popis: | Candida albicans mutants for phosphatidylserine (PS) synthase (cho1ΔΔ) and PS decarboxylase (psd1ΔΔ psd2ΔΔ) 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 cho1ΔΔ and psd1ΔΔ psd2ΔΔ 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 cho1ΔΔ mutant, which may be due to causing PS decarboxylase to run backwards and convert PE to PS. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|