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CRISPR/Cas9 Genome Editing To Demonstrate the Contribution of Cyp51A Gly138Ser to Azole Resistance in Aspergillus fumigatus.
Umeyama, Takashi; Hayashi, Yuta; Shimosaka, Hisaki; Inukai, Tatsuya; Yamagoe, Satoshi; Takatsuka, Shogo; Hoshino, Yasutaka; Nagi, Minoru; Nakamura, Shigeki; Kamei, Katsuhiko; Ogawa, Kenji; Miyazaki, Yoshitsugu.
Afiliação
  • Umeyama T; Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Tokyo, Japan umeyama@nih.go.jp.
  • Hayashi Y; Department of Respiratory Medicine, National Hospital Organization Higashinagoya National Hospital, Aichi, Japan.
  • Shimosaka H; Department of Clinical Laboratory, National Hospital Organization Higashinagoya National Hospital, Aichi, Japan.
  • Inukai T; Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Tokyo, Japan.
  • Yamagoe S; Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Tokyo, Japan.
  • Takatsuka S; Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Tokyo, Japan.
  • Hoshino Y; Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Tokyo, Japan.
  • Nagi M; Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Tokyo, Japan.
  • Nakamura S; Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Tokyo, Japan.
  • Kamei K; Medical Mycology Research Center, Chiba University, Chiba, Japan.
  • Ogawa K; Department of Respiratory Medicine, National Hospital Organization Higashinagoya National Hospital, Aichi, Japan.
  • Miyazaki Y; Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Tokyo, Japan.
Antimicrob Agents Chemother ; 62(9)2018 09.
Article em En | MEDLINE | ID: mdl-29914956
ABSTRACT
A pan-azole-resistant Aspergillus fumigatus strain with the cyp51A mutations Gly138Ser and Asn248Lys was isolated from a patient receiving long-term voriconazole treatment. PCR fragments containing cyp51A with the mutations were introduced along with the Cas9 protein and single guide RNA into the azole-resistant/susceptible strains. Recombinant strains showed increased susceptibility via the replacement of Ser138 by glycine. Genetic recombination, which has been hampered thus far in clinical isolates, can now be achieved using CRISPR/Cas9 genome editing.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Aspergilose / Aspergillus fumigatus / Proteínas Fúngicas / Sistema Enzimático do Citocromo P-450 / Farmacorresistência Fúngica / Voriconazol / Edição de Genes / Antifúngicos Limite: Aged / Humans / Male Idioma: En Revista: Antimicrob Agents Chemother Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Japão
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Aspergilose / Aspergillus fumigatus / Proteínas Fúngicas / Sistema Enzimático do Citocromo P-450 / Farmacorresistência Fúngica / Voriconazol / Edição de Genes / Antifúngicos Limite: Aged / Humans / Male Idioma: En Revista: Antimicrob Agents Chemother Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Japão