Chia Nan University of Pharmacy & Science Institutional Repository:Item 310902800/30913
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    Title: RNA polymerase B subunit gene mutations in biofilm-embedded methicillin-resistant Staphylococcus aureus following rifampin treatment
    Authors: Tang, Hung-Jen
    Lai, Chih-Cheng
    Hsueh, Po-Ren
    Chen, Chi-Chung
    Wu, Kuan-Ying
    Lin, Yi-Chung
    Zhang, Chun-Cheng
    Weng, Tzu-Chieh
    Chiu, Yu-Hsin
    Toh, Han-Siong
    Chiang, Shyh-Ren
    Yu, Wen-Liang
    Ko, Wen-Chien
    Chuang, Yin-Ching
    Contributors: Chi Mei Med Ctr, Dept Med
    Chia Nan Univ Pharm & Sci, Dept Hlth & Nutr
    Chi Mei Med Ctr, Dept Intens Care Med
    Natl Taiwan Univ Hosp, Dept Lab & Internal Med
    Natl Taiwan Univ, Coll Med
    Chi Mei Med Ctr, Dept Med Res
    Natl Cheng Kung Univ, Med Coll & Hosp, Inst Biotechnol
    Chi Mei Med Ctr, Dept Internal Med
    Natl Cheng Kung Univ, Med Coll & Hosp, Dept Med
    Keywords: biofilm-embedded MRSA
    mutations
    rpoB gene
    Date: 2016-06
    Issue Date: 2018-01-18 11:37:49 (UTC+8)
    Publisher: Elsevier Taiwan
    Abstract: Background/Purpose: This study was conducted to compare the mutation rates of different rpoB sites and rifampin minimum inhibitory concentration (MIC) changes prior to and after rifampin therapy for biofilm-embedded methicillin-resistant Staphylococcus aureus (MRSA) isolates. Methods: The screening of rifampin-resistant MRSA isolates, from the biofilm at Day 5 with or without exposure to the susceptible breakpoint concentration of rifampin recommended by the Clinical and Laboratory Standards Institute (1 mg/L), was conducted using agar plates containing rifampin. A partial fragment of RNA polymerase B subunit gene (rpoB), including clusters I and II, was amplified and sequenced. The rifampin MIC values and mutation frequencies at different sites of rpoB were measured and evaluated in rifampicin-resistant isolates. Results: Rifampin-resistant mutants could be selected from all of 39 randomly selected rifampin-susceptible MRSA isolates in the biofilm model. The spontaneous mutation frequency ranged from 1.00 x 10(-4) to 3.85 x 10(-7). Mutation at codon 481 was most commonly found at 35 (89.7%) of 39 MRSA isolates. Without rifampin induction, the MIC ranged between 0.125 mg/L and 1024 mg/L and mutation sites included cluster I 464, 466, 468, 471, 474, 477, 481, 484, 486 and cluster II 519, 527, 529 with the percentage of 471 (35.9%), 477 (33.3%), 481 (53.8%), and 484 (35.9%). Conversely, with the induction of rifampin, the MIC value ranged similar to 256-1024 mg/L. The mutation sites that were more concentrated included 468 (17.9%), 477 (30.8%), 481 (89.7%), 484 (17.9%), and 486 (33.3%). Conclusion: We documented high rifampin resistance induction activity when MRSA was engaged in biofilm with rifampin exposure. Monotherapy seems to be inadequate for MRSA in biofilm. There is an urgent need for developing effective combination therapies with less rifampin resistance-inducing activities for treating MRSA in biofilms. Copyright (C) 2015, Taiwan Society of Microbiology. Published by Elsevier Taiwan LLC.
    Relation: Journal of Microbiology Immunology and Infection, v.49 n.3, pp.394-401
    Appears in Collections:[Dept. of Health and Nutrition (including master's program)] Periodical Articles

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