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RamA upregulates multidrug resistance efflux pumps AcrAB and OqxAB in Klebsiella pneumoniae.
Xu, Qingqing; Sheng, Zike; Hao, Min; Jiang, Jianping; Ye, Meiping; Chen, Yijian; Xu, Xiaogang; Guo, Qinglan; Wang, Minggui.
Afiliación
  • Xu Q; Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China, and Key Laboratory of Clinical Pharmacology of Antibiotics, National Health Commission of PR China.
  • Sheng Z; Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Hao M; Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China, and Key Laboratory of Clinical Pharmacology of Antibiotics, National Health Commission of PR China.
  • Jiang J; Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China, and Key Laboratory of Clinical Pharmacology of Antibiotics, National Health Commission of PR China.
  • Ye M; Sexually Transmitted Disease Institute, Shanghai Skin Disease Hospital, Shanghai, China.
  • Chen Y; Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China, and Key Laboratory of Clinical Pharmacology of Antibiotics, National Health Commission of PR China.
  • Xu X; Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China, and Key Laboratory of Clinical Pharmacology of Antibiotics, National Health Commission of PR China; National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China.
  • Guo Q; Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China, and Key Laboratory of Clinical Pharmacology of Antibiotics, National Health Commission of PR China; National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China.
  • Wang M; Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China, and Key Laboratory of Clinical Pharmacology of Antibiotics, National Health Commission of PR China; National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China. Electronic
Int J Antimicrob Agents ; 57(2): 106251, 2021 Feb.
Article en En | MEDLINE | ID: mdl-33259915
Overexpression of the acrAB genes regulated by RamA and overexpression of oqxAB regulated by RarA have been reported to mediate multidrug resistance in Gram-negative bacilli. In this study, regulation of acrAB and oqxAB simultaneously by the global regulator RamA was investigated in a multidrug-resistant Klebsiella pneumoniae clinical isolate (KP22) resistant to tigecycline and other antimicrobials. KP22 overexpressed ramA due to a ramR mutation, along with an unexpected overexpression of oqxB. Deletion of ramA led to a 16-fold decrease in the tigecycline minimum inhibitory concentration (MIC) with decreased expression of acrB (4.3-fold) and oqxB (7.1-fold) compared with KP22. Transcomplementation of KP22ΔramA with the wild-type ramA gene restored the tigecycline MIC and upregulation of the acrB (3.9-fold) and oqxB (4.0-fold) genes compared with KP22. When oqxB was knocked out, MICs of ciprofloxacin, olaquindox and nitrofurantoin were considerably decreased, while deletion of acrB led to MIC decreases for cefepime, piperacillin/tazobactam and tigecycline in addition to the above three antimicrobials. The results of electrophoretic mobility shift assay showed that RamA could bind the promoter regions of both the acrAB and oqxAB operons. This study demonstrates for the first time that RamA can directly regulate multidrug resistance efflux pumps AcrAB and OqxAB in K. pneumoniae.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas de Transporte de Membrana / Proteínas Bacterianas / Klebsiella pneumoniae Límite: Humans Idioma: En Revista: Int J Antimicrob Agents Año: 2021 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas de Transporte de Membrana / Proteínas Bacterianas / Klebsiella pneumoniae Límite: Humans Idioma: En Revista: Int J Antimicrob Agents Año: 2021 Tipo del documento: Article Pais de publicación: Países Bajos