Functional characterization of Candida albicans Hos2 histone deacetylase [v3; ref status: indexed, http://f1000r.es/3xh]
Candida albicans is a mucosal commensal organism capable of causing superficial (oral and vaginal thrush) infections in immune normal hosts, but is a major pathogen causing systemic and mucosal infections in immunocompromised individuals. Azoles have been very effective anti-fungal agents and the ma...
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F1000 Research Ltd
2014-07-01
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| author | G Karthikeyan Maneesh Paul-Satyaseela Nachiappan Dhatchana Moorthy Radha Gopalaswamy Shridhar Narayanan |
| author_facet | G Karthikeyan Maneesh Paul-Satyaseela Nachiappan Dhatchana Moorthy Radha Gopalaswamy Shridhar Narayanan |
| author_sort | G Karthikeyan |
| collection | DOAJ |
| description | Candida albicans is a mucosal commensal organism capable of causing superficial (oral and vaginal thrush) infections in immune normal hosts, but is a major pathogen causing systemic and mucosal infections in immunocompromised individuals. Azoles have been very effective anti-fungal agents and the mainstay in treating opportunistic mold and yeast infections. Azole resistant strains have emerged compromising the utility of this class of drugs. It has been shown that azole resistance can be reversed by the co-administration of a histone deacetylase (HDAC) inhibitor, suggesting that resistance is mediated by epigenetic mechanisms possibly involving Hos2, a fungal deacetylase. We report here the cloning and functional characterization of HOS2 (HighOsmolarity Sensitive), a gene coding for fungal histone deacetylase from C. albicans. Inhibition studies showed that Hos2 is susceptible to pan inhibitors such as trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA), but is not inhibited by class I inhibitors such as MS-275. This in vitro enzymatic assay, which is amenable to high throughput could be used for screening potent fungal Hos2 inhibitors that could be a potential anti-fungal adjuvant. Purified Hos2 protein consistently deacetylated tubulins, rather than histones from TSA-treated cells. Hos2 has been reported to be a putative NAD+ dependent histone deacetylase, a feature of sirtuins. We assayed for sirtuin activation with resveratrol and purified Hos2 protein and did not find any sirtuin activity. |
| first_indexed | 2024-12-19T07:04:18Z |
| format | Article |
| id | doaj.art-0069a83409d2428b8d5bb6dce780ada0 |
| institution | Directory Open Access Journal |
| issn | 2046-1402 |
| language | English |
| last_indexed | 2024-12-19T07:04:18Z |
| publishDate | 2014-07-01 |
| publisher | F1000 Research Ltd |
| record_format | Article |
| series | F1000Research |
| spelling | doaj.art-0069a83409d2428b8d5bb6dce780ada02022-12-21T20:31:19ZengF1000 Research LtdF1000Research2046-14022014-07-01210.12688/f1000research.2-238.v35093Functional characterization of Candida albicans Hos2 histone deacetylase [v3; ref status: indexed, http://f1000r.es/3xh]G Karthikeyan0Maneesh Paul-Satyaseela1Nachiappan Dhatchana Moorthy2Radha Gopalaswamy3Shridhar Narayanan4Drug Discovery Research, Orchid Chemicals and Pharmaceuticals Limited, Chennai, 600 119, IndiaCurrent address: Samrud Foundation for Health & Research, Bangalore, 560106, IndiaDrug Discovery Research, Orchid Chemicals and Pharmaceuticals Limited, Chennai, 600 119, IndiaDrug Discovery Research, Orchid Chemicals and Pharmaceuticals Limited, Chennai, 600 119, IndiaCurrent address: AstraZeneca India Pvt. Ltd, Bengaluru, 560024, IndiaCandida albicans is a mucosal commensal organism capable of causing superficial (oral and vaginal thrush) infections in immune normal hosts, but is a major pathogen causing systemic and mucosal infections in immunocompromised individuals. Azoles have been very effective anti-fungal agents and the mainstay in treating opportunistic mold and yeast infections. Azole resistant strains have emerged compromising the utility of this class of drugs. It has been shown that azole resistance can be reversed by the co-administration of a histone deacetylase (HDAC) inhibitor, suggesting that resistance is mediated by epigenetic mechanisms possibly involving Hos2, a fungal deacetylase. We report here the cloning and functional characterization of HOS2 (HighOsmolarity Sensitive), a gene coding for fungal histone deacetylase from C. albicans. Inhibition studies showed that Hos2 is susceptible to pan inhibitors such as trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA), but is not inhibited by class I inhibitors such as MS-275. This in vitro enzymatic assay, which is amenable to high throughput could be used for screening potent fungal Hos2 inhibitors that could be a potential anti-fungal adjuvant. Purified Hos2 protein consistently deacetylated tubulins, rather than histones from TSA-treated cells. Hos2 has been reported to be a putative NAD+ dependent histone deacetylase, a feature of sirtuins. We assayed for sirtuin activation with resveratrol and purified Hos2 protein and did not find any sirtuin activity.http://f1000research.com/articles/2-238/v3Medical MicrobiologyMicrobial Evolution & Genomics |
| spellingShingle | G Karthikeyan Maneesh Paul-Satyaseela Nachiappan Dhatchana Moorthy Radha Gopalaswamy Shridhar Narayanan Functional characterization of Candida albicans Hos2 histone deacetylase [v3; ref status: indexed, http://f1000r.es/3xh] F1000Research Medical Microbiology Microbial Evolution & Genomics |
| title | Functional characterization of Candida albicans Hos2 histone deacetylase [v3; ref status: indexed, http://f1000r.es/3xh] |
| title_full | Functional characterization of Candida albicans Hos2 histone deacetylase [v3; ref status: indexed, http://f1000r.es/3xh] |
| title_fullStr | Functional characterization of Candida albicans Hos2 histone deacetylase [v3; ref status: indexed, http://f1000r.es/3xh] |
| title_full_unstemmed | Functional characterization of Candida albicans Hos2 histone deacetylase [v3; ref status: indexed, http://f1000r.es/3xh] |
| title_short | Functional characterization of Candida albicans Hos2 histone deacetylase [v3; ref status: indexed, http://f1000r.es/3xh] |
| title_sort | functional characterization of candida albicans hos2 histone deacetylase v3 ref status indexed http f1000r es 3xh |
| topic | Medical Microbiology Microbial Evolution & Genomics |
| url | http://f1000research.com/articles/2-238/v3 |
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