Homozygous deletion of ATC1 and NTC1 genes in Candida parapsilosis abolishes trehalase activity and affects cell growth, sugar metabolism, stress resistance, infectivity and biofilm formation

Sánchez-Fresneda, Ruth; Guirao-Abad, José P.; Martínez‐Esparza, María; Maicas, Sergi; Valentı́n, Eulogio; Argüelles, Juan-Carlos

doi:10.1016/j.fgb.2015.10.007

Cited by 13 publications

(23 citation statements)

References 63 publications

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“…Gácser et al (17) applied the C. albicans constructs directly to C. parapsilosis, whereas Ding and Butler (18) adapted it by replacing the promoters driving the expression of SAT1 and FLP with the orthologous sequences from C. parapsilosis. The SAT1 flipper cassette has since been used to delete several genes in C. parapsilosis (60,(126)(127)(128)(129)(130)(131)(132)(133).…”

Section: Genetic Toolboxmentioning

confidence: 99%

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Candida parapsilosis: from Genes to the Bedside

et al. 2019

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SUMMARY Patients with suppressed immunity are at the highest risk for hospital-acquired infections. Among these, invasive candidiasis is the most prevalent systemic fungal nosocomial infection. Over recent decades, the combined prevalence of non-albicans Candida species outranked Candida albicans infections in several geographical regions worldwide, highlighting the need to understand their pathobiology in order to develop effective treatment and to prevent future outbreaks. Candida parapsilosis is the second or third most frequently isolated Candida species from patients. Besides being highly prevalent, its biology differs markedly from that of C. albicans, which may be associated with C. parapsilosis’ increased incidence. Differences in virulence, regulatory and antifungal drug resistance mechanisms, and the patient groups at risk indicate that conclusions drawn from C. albicans pathobiology cannot be simply extrapolated to C. parapsilosis. Such species-specific characteristics may also influence their recognition and elimination by the host and the efficacy of antifungal drugs. Due to the availability of high-throughput, state-of-the-art experimental tools and molecular genetic methods adapted to C. parapsilosis, genome and transcriptome studies are now available that greatly contribute to our understanding of what makes this species a threat. In this review, we summarize 10 years of findings on C. parapsilosis pathogenesis, including the species’ genetic properties, transcriptome studies, host responses, and molecular mechanisms of virulence. Antifungal susceptibility studies and clinician perspectives are discussed. We also present regional incidence reports in order to provide an updated worldwide epidemiology summary.

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Section: Genetic Toolboxmentioning

confidence: 99%

“…Many of the genes upregulated under both conditions encode proteins involved in fatty acid (FA) biosynthesis or glycolysis. Hydrolytic lipase secretion as well as trehalose metabolism also influence biofilm development (17,132).…”

Section: Biofilm Formationmentioning

confidence: 99%

Candida parapsilosis: from Genes to the Bedside

et al. 2019

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“…These results provide further support on the inability of these mutant cells to mobilize endogenous trehalose or to hydrolyze exogenous disaccharide during their growth cycle [23]. The corresponding MICs values for both the parental and atc1∆/ntc1∆ strains were then calculated as 0.5 µg/ml for Fluconazole (FLC) and 0.15 µg/ml for Itraconazole (ITC), following the EUCAST protocol.…”

Section: Cell Survival Rate Of C Parapsilosis After Treatment With Az...mentioning

confidence: 84%

“…The C. parapsilosis strains used in this study have been reported elsewhere [10,23]. Liquid cultures were grown at 37ºC by shaking in YPD medium consisting of 2% peptone, 1% yeast extract and 2% glucose.…”

Section: Strains and Growth Conditionsmentioning

confidence: 99%

“…In C. parapsilosis, a single gene encodes both enzymes called neutral trehalase (Cp-NTC1) and acid trehalase (CpATC1) [10,23]. Enzymatic assays revealed the lack of any detectable trehalase activity (lower than 0.3 units/mg protein) during the growth cycle on a glucose-containing medium (YPD) of a homozygous C. parapsilosis null mutant atc1∆/ntc1∆ (Table 1), obtained by simultaneous disruption of the two individual genes [23].…”

Section: Cell Survival Rate Of C Parapsilosis After Treatment With Az...mentioning

confidence: 99%

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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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The many functions of carbohydrate-active enzymes in family GH65: diversity and application

De Beul,

Franceus,

Desmet

2024

Appl Microbiol Biotechnol

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Glycoside Hydrolase family 65 (GH65) is a unique family of carbohydrate-active enzymes. It is the first protein family to bring together glycoside hydrolases, glycoside phosphorylases and glycosyltransferases, thereby spanning a broad range of reaction types. These enzymes catalyze the hydrolysis, reversible phosphorolysis or synthesis of various α-glucosides, typically α-glucobioses or their derivatives. In this review, we present a comprehensive overview of the diverse reaction types and substrate specificities found in family GH65. We describe the determinants that control this remarkable diversity, as well as the applications of GH65 enzymes for carbohydrate synthesis. Supplementary Information The online version contains supplementary material available at 10.1007/s00253-024-13301-4.

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Homozygous deletion of ATC1 and NTC1 genes in Candida parapsilosis abolishes trehalase activity and affects cell growth, sugar metabolism, stress resistance, infectivity and biofilm formation

Cited by 13 publications

References 63 publications

Candida parapsilosis: from Genes to the Bedside

Candida parapsilosis: from Genes to the Bedside

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

The many functions of carbohydrate-active enzymes in family GH65: diversity and application

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