The involvement of the <i>Candida glabrata</i> trehalase enzymes in stress resistance and gut colonization

Ende, Mieke Van; Timmermans, Bea; Vanreppelen, Giel; Siscar-Lewin, Sofía; Fischer, Daniel; Wijnants, Stefanie; Romero, Celia Lobo; Yazdani, Saleh; Rogiers, Ona; Demuyser, Liesbeth; Zeebroeck, Griet Van; Cen, Yu-Ke; Kuchler, Karl; Brunke, Sascha; Dijck, Patrick Van

doi:10.1080/21505594.2020.1868825

Cited by 14 publications

(25 citation statements)

References 95 publications

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“…Atc1 is a cell wall-linked trehalase enzyme. C. glabrata trehalase enzymes were recently shown to be important for stress resistance [ 75 ], which is one of the factors important for the maintenance of fungal virulence.…”

Section: Resultsmentioning

confidence: 99%

Usingin vivotranscriptomics and RNA enrichment to identify genes involved in virulence ofCandida glabrata

et al. 2022

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Candida species are the most commonly isolated opportunistic fungal pathogens in humans. Candida albicans causes most of the diagnosed infections, closely followed by Candida glabrata . C. albicans is well studied, and many genes have been shown to be important for infection and colonization of the host. It is however less clear how C. glabrata infects the host. With the help of fungal RNA enrichment, we here investigated for the first time the transcriptomic profile of C. glabrata during urinary tract infection (UTI) in mice. In the UTI model, bladders and kidneys are major target organs and therefore fungal transcriptomes were addressed in these organs. Our results showed that, next to adhesins and proteases, nitrogen metabolism and regulation play a vital role during C. glabrata UTI. Genes involved in nitrogen metabolism were upregulated and among them we show that DUR1,2 (urea amidolyase) and GAP1 (amino acid permease) were important for virulence. Furthermore, we confirmed the importance of the glyoxylate cycle in the host and identified MLS1 (malate synthase) as an important gene necessary for C. glabrata virulence. In conclusion, our study shows with the support of in vivo transcriptomics how C. glabrata adapts to host conditions.

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Section: Resultsmentioning

confidence: 99%

Usingin vivotranscriptomics and RNA enrichment to identify genes involved in virulence ofCandida glabrata

et al. 2022

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“…Although trehalose hydrolysis has received less attention respect to the biosynthesis of disaccharide, recent evidence supports a major role of trehalases in the pathogenicity of several species of Candida [10,[20][21][22]. In this study, we have analyzed the hypothetical toxic effect of two azoles, FLC and ITC, against a C. parapsilosis null mutant atc1∆/ntc1∆, which lacks any enzymatic detectable trehalase activity (Table 1).…”

Section: Discussionmentioning

confidence: 99%

Lack of Functional Trehalase Activity in Candida Parapsilosis Increases Susceptibility to Itraconazole

Sánchez-Fresneda¹,

Muñoz-Megías²,

Guirao³

et al. 2022

Preprint

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Central metabolic pathways may play a major role in the virulence of pathogenic fungi. Here, we have investigated the susceptibility of a Candida parapsilosis mutant deficient in trehalase activity (atc1Δ/ntc1Δ strain) to the azolic compounds Fluconazole and Itraconazole. A time-course exposure to Itraconazole but not Fluconazole induced a significant degree of cell-killing in mutant cells compared to the parental strain. Flow cytometry determinations indicated that Itraconazole was able to induce a marked production of endogenous ROS together with a simultaneous increase in membrane potential, these effects being irrelevant after Fluconazole addition. Furthermore, only Itraconazole induced a significant synthesis of endogenous trehalose. The recorded impaired capacity of mutant cells to produce structured biofilms was further increased in the presence of both azoles, with Itraconazole being more effective than Fluconazole. Our results in the opportunistic pathogen yeast C. parapsilosis reinforce the study of trehalose metabolism as an attractive therapeutic target and allow extending the hypothesis that the generation of internal oxidative stress may be a component of the antifungal action exerted by the compounds currently available in medical practice.

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“…In fact, the glyoxylate shunt has been shown to be important for virulence in many fungal species [164] , [165] , [166] , [167] . Other storage molecules may play similar roles during macrophage interactions, such as trehalose in C. glabrata [168] .…”

Section: Host Adaptation and Immune Evasion Mechanismsmentioning

confidence: 99%

“Under Pressure” – How fungi evade, exploit, and modulate cells of the innate immune system

Lange¹,

Kasper²,

Gresnigt³

et al. 2023

Seminars in Immunology

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The involvement of the Candida glabrata trehalase enzymes in stress resistance and gut colonization

Cited by 14 publications

References 95 publications

Usingin vivotranscriptomics and RNA enrichment to identify genes involved in virulence ofCandida glabrata

Usingin vivotranscriptomics and RNA enrichment to identify genes involved in virulence ofCandida glabrata

Lack of Functional Trehalase Activity in Candida Parapsilosis Increases Susceptibility to Itraconazole

“Under Pressure” – How fungi evade, exploit, and modulate cells of the innate immune system

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