β(1,3)-glucan synthase complex from Alternaria infectoria, a rare dematiaceous human pathogen

J. Anjos; C. Fernandes; B.M.A. Silva; C. Quintas; A. Abrunheiro; N.A.R. Gow; T. Gonçalves

doi:10.3109/13693786.2012.675525

β(1,3)-glucan synthase complex from Alternaria infectoria, a rare dematiaceous human pathogen

J. Anjos, C. Fernandes, B.M.A. Silva, C. Quintas, A. Abrunheiro, N.A.R. Gow, T. Gonçalves

Research output: Contribution to journal › Article › peer-review

12 Citations (Scopus)

Abstract

The fungal cell wall polymer β-(1,3)-D-glucan is synthesized by the enzyme β-(1,3)-D-glucan synthase that is a complex composed of at least two proteins, Rho1p and Fks1p. Here, we report the nucleotide sequence of a single FKS gene and of the regulatory unit, RHO1 from the dematiaceous pathogenic fungus Alternaria infectoria. The predicted AiFks and AiRho share, respectively, 93% and 100% identity with that of Drechslera tritici-repentis. We also report that the sensitivity to caspofungin of eight different A. infectoria clinical strains is similar, with a MIC > 32 μg/ml and a MEC of 1 μg/ml, except for one strain which had a MEC of 1.4 μg/ml. This same strain exhibited one substitution at the hot spot 2, S1405A, compatible with less susceptible phenotypes, with the other seven strains having no mutations in either hot spot 1 or 2. The relative quantification of the expression of AiFKS and of AiRHO demonstrated a decrease in response to an exposure to caspofungin at 0.5 μg/ml.

Original language	English
Pages (from-to)	716-725
Number of pages	10
Journal	Medical Mycology
Volume	50
Issue number	7
DOIs	https://doi.org/10.3109/13693786.2012.675525
Publication status	Published - Oct 2012

Bibliographical note

This study was partly supported by a Merck, Sharp & Dohme, Inc. Medical School Grant (P-1599) and by a funded project by FCT-Fundação para a Ciência e Tecnologia (PTDC/SAUESA/108636/2008; co-funded by COMPETE and FEDER).
JA was recipient of a pos-doc fellowship within the scope of MSD Medical School Grant (P-1599). CF is a recipient of a Pos-doc Fellowship from FCT-Fundação para a Ciência e Tecnologia (SFRH/BPD/63733/2009). BMAS is a recipient
of a research fellowship whithin the scope of the FCT Project PTDC/SAUESA/108636/2008.
The authors acknowledge Dr. Cameron Douglas, of Merck & Co., Inc., for providing protocols, and helpful and stimulating discussions.
Declaration of interest: The authors have no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

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title = "β(1,3)-glucan synthase complex from Alternaria infectoria, a rare dematiaceous human pathogen",

abstract = "The fungal cell wall polymer β-(1,3)-D-glucan is synthesized by the enzyme β-(1,3)-D-glucan synthase that is a complex composed of at least two proteins, Rho1p and Fks1p. Here, we report the nucleotide sequence of a single FKS gene and of the regulatory unit, RHO1 from the dematiaceous pathogenic fungus Alternaria infectoria. The predicted AiFks and AiRho share, respectively, 93% and 100% identity with that of Drechslera tritici-repentis. We also report that the sensitivity to caspofungin of eight different A. infectoria clinical strains is similar, with a MIC > 32 μg/ml and a MEC of 1 μg/ml, except for one strain which had a MEC of 1.4 μg/ml. This same strain exhibited one substitution at the hot spot 2, S1405A, compatible with less susceptible phenotypes, with the other seven strains having no mutations in either hot spot 1 or 2. The relative quantification of the expression of AiFKS and of AiRHO demonstrated a decrease in response to an exposure to caspofungin at 0.5 μg/ml. ",

author = "J. Anjos and C. Fernandes and B.M.A. Silva and C. Quintas and A. Abrunheiro and N.A.R. Gow and T. Gon{\c c}alves",

note = "This study was partly supported by a Merck, Sharp & Dohme, Inc. Medical School Grant (P-1599) and by a funded project by FCT-Funda{\c c}{\~a}o para a Ci{\^e}ncia e Tecnologia (PTDC/SAUESA/108636/2008; co-funded by COMPETE and FEDER). JA was recipient of a pos-doc fellowship within the scope of MSD Medical School Grant (P-1599). CF is a recipient of a Pos-doc Fellowship from FCT-Funda{\c c}{\~a}o para a Ci{\^e}ncia e Tecnologia (SFRH/BPD/63733/2009). BMAS is a recipient of a research fellowship whithin the scope of the FCT Project PTDC/SAUESA/108636/2008. The authors acknowledge Dr. Cameron Douglas, of Merck & Co., Inc., for providing protocols, and helpful and stimulating discussions. Declaration of interest: The authors have no conflicts of interest. The authors alone are responsible for the content and writing of the paper. ",

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AU - Anjos, J.

AU - Fernandes, C.

AU - Silva, B.M.A.

AU - Quintas, C.

AU - Abrunheiro, A.

AU - Gow, N.A.R.

AU - Gonçalves, T.

N1 - This study was partly supported by a Merck, Sharp & Dohme, Inc. Medical School Grant (P-1599) and by a funded project by FCT-Fundação para a Ciência e Tecnologia (PTDC/SAUESA/108636/2008; co-funded by COMPETE and FEDER). JA was recipient of a pos-doc fellowship within the scope of MSD Medical School Grant (P-1599). CF is a recipient of a Pos-doc Fellowship from FCT-Fundação para a Ciência e Tecnologia (SFRH/BPD/63733/2009). BMAS is a recipient of a research fellowship whithin the scope of the FCT Project PTDC/SAUESA/108636/2008. The authors acknowledge Dr. Cameron Douglas, of Merck & Co., Inc., for providing protocols, and helpful and stimulating discussions. Declaration of interest: The authors have no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

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N2 - The fungal cell wall polymer β-(1,3)-D-glucan is synthesized by the enzyme β-(1,3)-D-glucan synthase that is a complex composed of at least two proteins, Rho1p and Fks1p. Here, we report the nucleotide sequence of a single FKS gene and of the regulatory unit, RHO1 from the dematiaceous pathogenic fungus Alternaria infectoria. The predicted AiFks and AiRho share, respectively, 93% and 100% identity with that of Drechslera tritici-repentis. We also report that the sensitivity to caspofungin of eight different A. infectoria clinical strains is similar, with a MIC > 32 μg/ml and a MEC of 1 μg/ml, except for one strain which had a MEC of 1.4 μg/ml. This same strain exhibited one substitution at the hot spot 2, S1405A, compatible with less susceptible phenotypes, with the other seven strains having no mutations in either hot spot 1 or 2. The relative quantification of the expression of AiFKS and of AiRHO demonstrated a decrease in response to an exposure to caspofungin at 0.5 μg/ml.

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DO - 10.3109/13693786.2012.675525

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JO - Medical Mycology

JF - Medical Mycology

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ER -

β(1,3)-glucan synthase complex from Alternaria infectoria, a rare dematiaceous human pathogen

Abstract

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