Functional characterization of Candida glabrata ORF, CAGL0M02233g for its role in stress tolerance and virulence

Gupta, Payal; Meena, Ramesh Chandra; Kumar, Neha

doi:10.1016/j.micpath.2020.104469

Cited by 11 publications

(10 citation statements)

References 38 publications

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“…The eradicating effect of EPTL on biofilm was evaluated by XTT reduction assay after 24 h of incubation (Gupta et al . 2020). Here, biofilm eradication potential (BEC) of EPTL is measured in terms of the number of biofilm cells removed from preformed biofilm as compared to untreated control.…”

Section: Methodsmentioning

confidence: 99%

Mechanistic insights into Candida biofilm eradication potential of eucalyptol

Gupta

Pruthi

Poluri

2020

J. Appl. Microbiol.

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Aim Candida‐associated fungal infections are prevalent in hospitalized and immune‐compromised patients. Their biofilm architecture and high rate of antifungal resistance make treatment challenging. Eucalyptol (EPTL), a monoterpene majorly present in the essential oil of eucalyptus is well known for curing respiratory infections. Hence, the present study investigated the anti‐biofilm efficacy of EPTL against the laboratory strains and clinical isolates of Candida to delineate its mode of action. Methods The effect of EPTL on the viability, biofilm formation, and mature biofilm of Candida strains was studied. Furthermore, its effect on cell cycle arrest, mitochondrial membrane potential (MMP), ROS generation, germ tube formation, ergosterol content and transcriptional expression of selected genes was also investigated. Results EPTL exhibited anti‐biofilm activity against mature and developing biofilm of Candida albicans and Candida glabrata along with their clinical isolates. The biochemical components and enzyme activity were differentially modulated in EPTL‐treated biofilm extracellular matrix. EPTL generated ROS and arrested cell cycle at the G1/S phase in both the species, while altered MMP was recorded in C. glabrata. Transcriptional analysis evidenced for differential gene expression of selected ABC transporters, secreted hydrolytic enzymes, and cell wall biogenesis in C. albicans/C. glabrata upon treating with EPTL. Conclusion The current data on anti‐biofilm activity of EPTL establish its candidacy for drug development or as an adjuvant with existing antifungal formulations. Significance and Impact of the Study Present investigation elucidates the mode of action of Eucalyptol as antifungal agent and would stand as a candidate for management of topical fungal infection.

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Section: Methodsmentioning

confidence: 99%

Mechanistic insights into Candida biofilm eradication potential of eucalyptol

Gupta

Pruthi

Poluri

2020

J. Appl. Microbiol.

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Section: Methodsmentioning

confidence: 99%

“…Biofilm inhibition and eradication activity of PA against C. glabrata and its isolates was studied in 96-well plates in RPMI media following the methods described elsewhere. 43 Briefly, log -phase cells at a cell density of 5 × 10 7 cells/mL in PBS were seeded into a multiwell plate (MTP). After 90 min of incubation at 37 °C, the PBS was replaced with RPMI with or without PA. After 24 h of incubation, wells were washed and the biofilm was quantified in terms of metabolic activity using XTT reduction assay.…”

Section: Methodsmentioning

confidence: 99%

Elucidating the Eradication Mechanism of Perillyl Alcohol against Candida glabrata Biofilms: Insights into the Synergistic Effect with Azole Drugs

Gupta

Poluri

2021

ACS Bio Med Chem Au

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Increased incidences of fungal infections and associated mortality have accelerated the need for effective and alternative therapeutics. Perillyl alcohol (PA) is a terpene produced by the hydroxylation of limonene via the mevalonate pathway. In pursuit of an alternative antifungal agent, we studied the effect of PA on the biofilm community of Candida glabrata and on different cellular pathways to decipher its mode of action. PA efficiently inhibited growth and eradicated biofilms by reducing carbohydrate and eDNA content in the extracellular matrix. PA reduced the activity of hydrolytic enzymes in the ECM of C. glabrata biofilm. The chemical profiling study has given insights into the overall mode of action of PA in C. glabrata and the marked involvement of the cell wall and membrane, ergosterol biosynthesis, oxidative stress, and DNA replication. The spectroscopic and RT-PCR studies suggested a strong interaction of PA with chitin, β-glucan, ergosterol, and efflux pump, thus indicating increased membrane fluidity in C. glabrata. Furthermore, the microscopic and flow cytometry analysis emphasized that PA facilitated the change in mitochondrial activity, increased Ca 2+ influx via overexpression of voltage-gated Ca 2+ channels, and enhanced cytochrome C release from mitochondria. In addition, PA interferes with DNA replication and thus hinders the cell cycle progression at the S-phase. All these studies together established that PA mitigates the C. glabrata biofilms by targeting multiple cellular pathways. Interestingly, PA also potentiated the efficacy of azole drugs, particularly miconazole, against C. glabrata and its clinical isolates. Conclusively, the study demonstrated the use of PA as an effective antifungal agent alone or in combination with FDA-approved conventional drugs for fungal biofilm eradication.

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“…Constitutive expression of CgRAD53 supports the growth of C. glabrata cells in the presence of MMS, HU and cobalt chloride. CgRAD53 is also involved in biofilm formation and thus shows a potential correlation with virulence in C. glabrata [101] . Furthermore, it is well known that ScRad53 and CaRad53 are phosphorylated in response to genotoxic stresses, but strikingly in C. glabrata , exposure to DNA damage stresses does not induce CgRad53 phosphorylation, suggesting alterable signaling DDR pathways.…”

Section: Dna Damage Response In Other Fungal Pathogensmentioning

confidence: 99%

DNA damage checkpoint and repair: From the budding yeast Saccharomyces cerevisiae to the pathogenic fungus Candida albicans

Yao

Feng

Zhang

et al. 2021

Computational and Structural Biotechnology Journal

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Cells are constantly challenged by internal or external genotoxic assaults, which may induce a high frequency of DNA lesions, leading to genome instability. Accumulation of damaged DNA is severe or even lethal to cells and can result in abnormal proliferation that can cause cancer in multicellular organisms, aging or cell death. Eukaryotic cells have evolved a comprehensive defence system termed the DNA damage response (DDR) to monitor and remove lesions in their DNA. The DDR has been extensively studied in the budding yeast Saccharomyces cerevisiae . Emerging evidence indicates that DDR genes in the pathogenic fungus Candida albicans show functional consistency with their orthologs in S. cerevisiae , but may act through distinct mechanisms. In particular, the DDR in C. albicans appears critical for resisting DNA damage stress induced by reactive oxygen species (ROS) produced from immune cells, and this plays a vital role in pathogenicity. Therefore, DDR genes could be considered as potential targets for clinical therapies. This review summarizes the identified DNA damage checkpoint and repair genes in C. albicans based on their orthologs in S. cerevisiae , and discusses their contribution to pathogenicity in C. albicans .

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Functional characterization of Candida glabrata ORF, CAGL0M02233g for its role in stress tolerance and virulence

Cited by 11 publications

References 38 publications

Mechanistic insights into Candida biofilm eradication potential of eucalyptol

Mechanistic insights into Candida biofilm eradication potential of eucalyptol

Elucidating the Eradication Mechanism of Perillyl Alcohol against Candida glabrata Biofilms: Insights into the Synergistic Effect with Azole Drugs

DNA damage checkpoint and repair: From the budding yeast Saccharomyces cerevisiae to the pathogenic fungus Candida albicans

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