Dataset Information

A Fox2-dependent fatty acid ß-oxidation pathway coexists both in peroxisomes and mitochondria of the ascomycete yeast Candida lusitaniae.

ABSTRACT: It is generally admitted that the ascomycete yeasts of the subphylum Saccharomycotina possess a single fatty acid ß-oxidation pathway located exclusively in peroxisomes, and that they lost mitochondrial ß-oxidation early during evolution. In this work, we showed that mutants of the opportunistic pathogenic yeast Candida lusitaniae which lack the multifunctional enzyme Fox2p, a key enzyme of the ß-oxidation pathway, were still able to grow on fatty acids as the sole carbon source, suggesting that C. lusitaniae harbored an alternative pathway for fatty acid catabolism. By assaying 14C?-palmitoyl-CoA consumption, we demonstrated that fatty acid catabolism takes place in both peroxisomal and mitochondrial subcellular fractions. We then observed that a fox2? null mutant was unable to catabolize fatty acids in the mitochondrial fraction, thus indicating that the mitochondrial pathway was Fox2p-dependent. This finding was confirmed by the immunodetection of Fox2p in protein extracts obtained from purified peroxisomal and mitochondrial fractions. Finally, immunoelectron microscopy provided evidence that Fox2p was localized in both peroxisomes and mitochondria. This work constitutes the first demonstration of the existence of a Fox2p-dependent mitochondrial ?-oxidation pathway in an ascomycetous yeast, C. lusitaniae. It also points to the existence of an alternative fatty acid catabolism pathway, probably located in peroxisomes, and functioning in a Fox2p-independent manner.

SUBMITTER: Gabriel F

PROVIDER: S-EPMC4259357 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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A Fox2-dependent fatty acid ß-oxidation pathway coexists both in peroxisomes and mitochondria of the ascomycete yeast Candida lusitaniae.

Gabriel Frédéric F Accoceberry Isabelle I Bessoule Jean-Jacques JJ Salin Bénédicte B Lucas-Guérin Marine M Manon Stephen S Dementhon Karine K Noël Thierry T

PloS one 20141208 12

It is generally admitted that the ascomycete yeasts of the subphylum Saccharomycotina possess a single fatty acid ß-oxidation pathway located exclusively in peroxisomes, and that they lost mitochondrial ß-oxidation early during evolution. In this work, we showed that mutants of the opportunistic pathogenic yeast Candida lusitaniae which lack the multifunctional enzyme Fox2p, a key enzyme of the ß-oxidation pathway, were still able to grow on fatty acids as the sole carbon source, suggesting that ...[more]

PMID: 25486052

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Project description:Candida lusitaniae is usually susceptible to echinocandins. Beta-1,3-glucan synthase encoded by FKS genes is the target of echinocandins. A few missense mutations in the C. lusitaniae FKS1 hot spot 1 (HS1) have been reported. We report here the rapid emergence of antifungal resistance in C. lusitaniae isolated during therapy with amphotericin B (AMB), caspofungin (CAS), and azoles for treatment of persistent candidemia in an immunocompromised child with severe enterocolitis and visceral adenoviral disease. As documented from restriction fragment length polymorphism (RFLP) and random amplified polymorphic DNA (RAPD) analysis, the five C. lusitaniae isolates examined were related to each other. From antifungal susceptibility and molecular analyses, 5 different profiles (P) were obtained. These profiles included the following: profile 1 (P1) (CAS MIC [?g/ml], 0.5; fluconazole [FLC] MIC, 0.25), determined while the patient was being treated with liposomal AMB for 3 months; P2 (FLC MIC [?g/ml], 0.25; CAS MIC, 4), while the patient was being treated with CAS for 2 weeks; P3 (CAS MIC [?g/ml], 0.5; FLC MIC, 32), while the patient was being treated with azoles and CAS initially followed by azoles alone for a week; P4 (CAS MIC [?g/ml], 8; FLC MIC, 8), while the patient was being treated with both drugs for 3 weeks; and P5 (AMB MIC [?g/ml], 0.125; CAS MIC, 8), while the patient was being treated with AMB and FLC for 2 weeks. CAS resistance was associated with resistance not only to micafungin and anidulafungin but also to AMB. Analysis of CAS resistance revealed 3 novel FKS1 mutations in CAS-resistant isolates (S638Y in P2; S631Y in P4; S638P in P5). While S638Y and -P are within HS1, S631Y is in close proximity to this domain but was confirmed to confer candin resistance using a site-directed mutagenesis approach. FLC resistance could be linked with overexpression of major facilitator gene 7 (MFS7) in C. lusitaniae P2 and P4 and was associated with resistance to 5-flurocytosine. This clinical report describes resistance of C. lusitaniae to all common antifungals. While candins or azole resistance followed monotherapy, multidrug antifungal resistance emerged during combined therapy.

Dataset Information

A Fox2-dependent fatty acid ß-oxidation pathway coexists both in peroxisomes and mitochondria of the ascomycete yeast Candida lusitaniae.

Publications

A Fox2-dependent fatty acid ß-oxidation pathway coexists both in peroxisomes and mitochondria of the ascomycete yeast Candida lusitaniae.

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