Characterization of Candida albicans biofilms : their formation, anti-fungal resistance, and differentiation

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.

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The in vitro formation of candida albicans biofilms on titanium discs and their susceptibility to an anti-fungal agent

10.5353/th_b4500777 ◽

2005 ◽

Author(s):

Hyden Ng

Keyword(s):

Candida Albicans ◽

Anti Fungal ◽

Candida Albicans Biofilms

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Characterization of the Dielectrophoretic Response of Different Candida Strains Using 3D Carbon Microelectrodes

Micromachines ◽

10.3390/mi11030255 ◽

2020 ◽

Vol 11 (3) ◽

pp. 255 ◽

Cited By ~ 3

Author(s):

Monsur Islam ◽

Devin Keck ◽

Jordon Gilmore ◽

Rodrigo Martinez-Duarte

Keyword(s):

Candida Albicans ◽

Candida Tropicalis ◽

Rapid Identification ◽

Candida Strain ◽

Life Threatening ◽

Rising Incidence ◽

Candida Infections ◽

Species Specific ◽

Anti Fungal

Bloodstream infection with Candida fungal cells remains one of the most life-threatening complications among hospitalized patients around the world. Although most of the cases are still due to Candida albicans, the rising incidence of infections caused by other Candida strains that may not respond to traditional anti-fungal treatments merits the development of a method for species-specific isolation of Candida. To this end, here we present the characterization of the dielectrophoresis (DEP) response of Candida albicans, Candida tropicalis and Candida parapsilosis. We complement such characterization with a study of the Candida cells morphology. The Candida strains exhibited subtle differences in their morphology and dimensions. All the Candida strains exhibited positive DEP in the range 10–500 kHz, although the strength of the DEP response was different for each Candida strain at different frequencies. Only Candida tropicalis showed positive DEP at 750 kHz. The current results show potential for manipulation and enrichment of a specific Candida strain at specific DEP conditions towards aiding in the rapid identification of Candida strains to enable the effective and timely treatment of Candida infections.

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Functional characterization of Candida albicans Hos2 histone deacetylase

F1000Research ◽

10.12688/f1000research.2-238.v1 ◽

2013 ◽

Vol 2 ◽

pp. 238 ◽

Cited By ~ 2

Author(s):

G Karthikeyan ◽

Maneesh Paul-Satyaseela ◽

Nachiappan Dhatchana Moorthy ◽

Radha Gopalaswamy ◽

Shridhar Narayanan

Keyword(s):

Candida Albicans ◽

Histone Deacetylase ◽

Trichostatin A ◽

Functional Characterization ◽

Gene Coding ◽

Normal Individuals ◽

Mold And Yeast ◽

Anti Fungal ◽

Inhibition Studies

Candida albicansis a mucosal commensal organism in normal individuals, 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 ofHOS2 (HighOsmolaritySensitive),a gene coding for fungal histone deacetylase fromC. 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 MS-275. Purified Hos2 protein consistently deacetylated tubulins, rather than histones from TSA-treated cells. Thisinvitroenzymatic assay, which is amenable to high throughput could be used for screening potent fungal Hos2 inhibitors that could be a potential anti-fungal adjuvant. 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.

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