Mechanisms of Resistance to Fenpropimorph and Terbinafine, Two Sterol Biosynthesis Inhibitors, in Nectria haematococca, a Phytopathogenic Fungus

Falandre, Alexandrine Lasseron-De; Debieu, Danièle; Bach, Jocelyne; Malosse, Christian; Leroux, Pierre

doi:10.1006/pest.1999.2424

Cited by 10 publications

(8 citation statements)

References 28 publications

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“…and Trichophyton spp. as well as suspension culture of celery cells Apium graveolens (Yates et al 1991;Ryder 1992;Lasseron-De Falandre et al 1999) which could interfere with membrane function and finally result in cell damage (Ryder 1992). Data with an asterisk indicate a significant difference from the control at P \ 0.05 l, specific growth rate; X max , maximum biomass concentration; Y x/glu , growth yield coefficient based on glucose…”

Section: Discussionmentioning

confidence: 99%

Enhanced production of squalene in the thraustochytrid Aurantiochytrium mangrovei by medium optimization and treatment with terbinafine

Fan

Aki

Chen

et al. 2010

World J Microbiol Biotechnol

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Squalene is an effective chemopreventive agent in reducing the incident of coronary heart disease and cancer. It is also a strong antioxidant used extensively in the food and cosmetic industries. Microbial sources of squalene are being explored in recent years. The objective of this study is to increase the squalene content and yield in the thraustochytrid, Aurantiochytrium mangrovei FB3 through medium optimization and the treatment with terbinafine, an inhibitor of squalene monooxygenase in the sterol biosynthetic pathway. The highest biomass concentration of 21.2 g l(-1) was obtained at a glucose concentration of 60 g l(-1), while the highest specific growth rate of 0.077 h(-1) and the growth yield coefficient of 0.44 g g(-1) based on glucose were achieved at a lower glucose concentration (30 g l(-1)). The addition of terbinafine led to a slight inhibition of cell growth whereas an obvious increase in squalene content was observed at terbinafine concentrations of 10 and 100 mg l(-1), which corresponded to an increase of 36 and 40% in squalene content, respectively compared to the control. The addition of terbinafine was thus effective in inducing the accumulation of squalene in A. mangrovei. This study not only demonstrated the production potential of squalene by A. mangrovei, but also provided novel information on the accumulation effect of terbinafine on the biosynthesis of an essential intermediate involved in sterol metabolic pathway.

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Section: Discussionmentioning

confidence: 99%

Enhanced production of squalene in the thraustochytrid Aurantiochytrium mangrovei by medium optimization and treatment with terbinafine

Fan

Aki

Chen

et al. 2010

World J Microbiol Biotechnol

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“…However, the terbinafine‐resistant mutants of Nectria haematococca , a phytopathogenic fungus, contain at least 10 times more squalene than the wild‐type strain, possibly suggesting the presence of a modified squalene epoxidase in these mutants. Thus, a reduced affinity of the squalene epoxide for both the substrate and the fungicide could explain terbinafine resistance in these mutants (Lasseron‐De Falandre et al . 1999).…”

Section: Introductionmentioning

confidence: 99%

Identification of genes involved in terbinafine resistance in Aspergillus nidulans

Rocha

Almeida

Martinez-Rossi

2002

Lett Appl Microbiol

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Aims: To determine the pattern and the genetic basis of resistance to terbinafine, a drug extensively used for the treatment of fungal infections in humans. Methods and Results: Four resistant mutants from Aspergillus nidulans isolated after irradiation with ultraviolet light were crossed with the master strain F (MSF). Genetic analysis revealed that a single gene, located on chromosome IV, is responsible for resistance to terbinafine and that the alleles responsible for this resistance in these mutants are of a codominant or dominant nature at high terbinafine concentrations. Furthermore, the interaction of this mutation with another one identified on chromosome II causes the double mutant to be highly resistant. Conclusions: Periodic surveillance of antimycotic susceptibility would be an important measure in detecting the emergence and spread of resistance. Mutation in a single gene could be responsible for resistance to terbinafine and a genic interaction may be responsible for a higher level of antimycotic resistance. Significance and Impact of the Study: The understanding of the mechanisms that lead to changes in the sensitivity of a fungus to a given antifungal agent is important both in order to define strategies for the use of such agent and to guide the development of new antifungal agents.

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“…In one case, a modified squalene epoxidase with reduced affinity for terbinafine conferred terbinafine resistance to Nectria haematococca mutants (15) and, in another, a Candida albicans strain was resistant to terbinafine due to activation of the multidrug efflux transporter CDR2 (35). Also, a C. albicans mutant carrying CDR1 deletion resulted in azoles and terbinafine hypersusceptibility (36).…”

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confidence: 99%

Terbinafine Resistance Mediated by Salicylate 1-Monooxygenase inAspergillus nidulans

Graminha

Rocha

Prade

et al. 2004

Antimicrob Agents Chemother

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Resistance to antifungal agents is a recurring and growing problem among patients with systemic fungal infections. UV-induced Aspergillus nidulans mutants resistant to terbinafine have been identified, and we report here the characterization of one such gene. A sib-selected, 6.6-kb genomic DNA fragment encodes a salicylate 1-monooxygenase (salA), and a fatty acid synthase subunit (fasC) confers terbinafine resistance upon transformation of a sensitive strain. Subfragments carrying salA but not fasC confer terbinafine resistance. salA is present as a single-copy gene on chromosome VI and encodes a protein of 473 amino acids that is homologous to salicylate 1-monooxygenase, a well-characterized naphthalene-degrading enzyme in bacteria. salA transcript accumulation analysis showed terbinafine-dependent induction in the wild type and the UV-induced mutant Terb7, as well as overexpression in a strain containing the salA subgenomic DNA fragment, probably due to the multicopy effect caused by the transformation event. Additional naphthalene degradation enzyme-coding genes are present in fungal genomes, suggesting that resistance could follow degradation of the naphthalene ring contained in terbinafine.

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Mechanisms of Resistance to Fenpropimorph and Terbinafine, Two Sterol Biosynthesis Inhibitors, in Nectria haematococca, a Phytopathogenic Fungus

Cited by 10 publications

References 28 publications

Enhanced production of squalene in the thraustochytrid Aurantiochytrium mangrovei by medium optimization and treatment with terbinafine

Enhanced production of squalene in the thraustochytrid Aurantiochytrium mangrovei by medium optimization and treatment with terbinafine

Identification of genes involved in terbinafine resistance in Aspergillus nidulans

Terbinafine Resistance Mediated by Salicylate 1-Monooxygenase inAspergillus nidulans

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