Candida albicans PPG1, a serine/threonine phosphatase, plays a vital role in central carbon metabolisms under filament-inducing conditions: A multi-omics approach
Candida albicans is the leading cause of life-threatening bloodstream candidiasis, especially among immunocompromised patients. The reversible morphological transition from yeast to hyphal filaments in response to host environmental cues facilitates C. albicans tissue invasion, immune evasion, and d...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2021-01-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8651141/?tool=EBI |
| _version_ | 1819181120199065600 |
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| author | Mohammad Tahseen A. L. Bataineh Nelson Cruz Soares Mohammad Harb Semreen Stefano Cacciatore Nihar Ranjan Dash Mohamad Hamad Muath Khairi Mousa Jasmin Shafarin Abdul Salam Mutaz F. Al Gharaibeh Luiz F. Zerbini Mawieh Hamad |
| author_facet | Mohammad Tahseen A. L. Bataineh Nelson Cruz Soares Mohammad Harb Semreen Stefano Cacciatore Nihar Ranjan Dash Mohamad Hamad Muath Khairi Mousa Jasmin Shafarin Abdul Salam Mutaz F. Al Gharaibeh Luiz F. Zerbini Mawieh Hamad |
| author_sort | Mohammad Tahseen A. L. Bataineh |
| collection | DOAJ |
| description | Candida albicans is the leading cause of life-threatening bloodstream candidiasis, especially among immunocompromised patients. The reversible morphological transition from yeast to hyphal filaments in response to host environmental cues facilitates C. albicans tissue invasion, immune evasion, and dissemination. Hence, it is widely considered that filamentation represents one of the major virulence properties in C. albicans. We have previously characterized Ppg1, a PP2A-type protein phosphatase that controls filament extension and virulence in C. albicans. This study conducted RNA sequencing analysis of samples obtained from C. albicans wild type and ppg1Δ/Δ strains grown under filament-inducing conditions. Overall, ppg1Δ/Δ strain showed 1448 upregulated and 710 downregulated genes, representing approximately one-third of the entire annotated C. albicans genome. Transcriptomic analysis identified significant downregulation of well-characterized genes linked to filamentation and virulence, such as ALS3, HWP1, ECE1, and RBT1. Expression analysis showed that essential genes involved in C. albicans central carbon metabolisms, including GDH3, GPD1, GPD2, RHR2, INO1, AAH1, and MET14 were among the top upregulated genes. Subsequent metabolomics analysis of C. albicans ppg1Δ/Δ strain revealed a negative enrichment of metabolites with carboxylic acid substituents and a positive enrichment of metabolites with pyranose substituents. Altogether, Ppg1 in vitro analysis revealed a link between metabolites substituents and filament formation controlled by a phosphatase to regulate morphogenesis and virulence. |
| first_indexed | 2024-12-22T22:25:11Z |
| format | Article |
| id | doaj.art-86ea3e651e3c4229a12870200067af94 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T22:25:11Z |
| publishDate | 2021-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-86ea3e651e3c4229a12870200067af942022-12-21T18:10:34ZengPublic Library of Science (PLoS)PLoS ONE1932-62032021-01-011612Candida albicans PPG1, a serine/threonine phosphatase, plays a vital role in central carbon metabolisms under filament-inducing conditions: A multi-omics approachMohammad Tahseen A. L. BatainehNelson Cruz SoaresMohammad Harb SemreenStefano CacciatoreNihar Ranjan DashMohamad HamadMuath Khairi MousaJasmin Shafarin Abdul SalamMutaz F. Al GharaibehLuiz F. ZerbiniMawieh HamadCandida albicans is the leading cause of life-threatening bloodstream candidiasis, especially among immunocompromised patients. The reversible morphological transition from yeast to hyphal filaments in response to host environmental cues facilitates C. albicans tissue invasion, immune evasion, and dissemination. Hence, it is widely considered that filamentation represents one of the major virulence properties in C. albicans. We have previously characterized Ppg1, a PP2A-type protein phosphatase that controls filament extension and virulence in C. albicans. This study conducted RNA sequencing analysis of samples obtained from C. albicans wild type and ppg1Δ/Δ strains grown under filament-inducing conditions. Overall, ppg1Δ/Δ strain showed 1448 upregulated and 710 downregulated genes, representing approximately one-third of the entire annotated C. albicans genome. Transcriptomic analysis identified significant downregulation of well-characterized genes linked to filamentation and virulence, such as ALS3, HWP1, ECE1, and RBT1. Expression analysis showed that essential genes involved in C. albicans central carbon metabolisms, including GDH3, GPD1, GPD2, RHR2, INO1, AAH1, and MET14 were among the top upregulated genes. Subsequent metabolomics analysis of C. albicans ppg1Δ/Δ strain revealed a negative enrichment of metabolites with carboxylic acid substituents and a positive enrichment of metabolites with pyranose substituents. Altogether, Ppg1 in vitro analysis revealed a link between metabolites substituents and filament formation controlled by a phosphatase to regulate morphogenesis and virulence.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8651141/?tool=EBI |
| spellingShingle | Mohammad Tahseen A. L. Bataineh Nelson Cruz Soares Mohammad Harb Semreen Stefano Cacciatore Nihar Ranjan Dash Mohamad Hamad Muath Khairi Mousa Jasmin Shafarin Abdul Salam Mutaz F. Al Gharaibeh Luiz F. Zerbini Mawieh Hamad Candida albicans PPG1, a serine/threonine phosphatase, plays a vital role in central carbon metabolisms under filament-inducing conditions: A multi-omics approach PLoS ONE |
| title | Candida albicans PPG1, a serine/threonine phosphatase, plays a vital role in central carbon metabolisms under filament-inducing conditions: A multi-omics approach |
| title_full | Candida albicans PPG1, a serine/threonine phosphatase, plays a vital role in central carbon metabolisms under filament-inducing conditions: A multi-omics approach |
| title_fullStr | Candida albicans PPG1, a serine/threonine phosphatase, plays a vital role in central carbon metabolisms under filament-inducing conditions: A multi-omics approach |
| title_full_unstemmed | Candida albicans PPG1, a serine/threonine phosphatase, plays a vital role in central carbon metabolisms under filament-inducing conditions: A multi-omics approach |
| title_short | Candida albicans PPG1, a serine/threonine phosphatase, plays a vital role in central carbon metabolisms under filament-inducing conditions: A multi-omics approach |
| title_sort | candida albicans ppg1 a serine threonine phosphatase plays a vital role in central carbon metabolisms under filament inducing conditions a multi omics approach |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8651141/?tool=EBI |
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