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分析泰乐菌素胁迫下 ATCC 700794 的多药耐药性。

Analysis of multidrug resistance in ATCC 700794 under tylosin stress.

机构信息

College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang, P.R. China.

Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Northeast Agricultural University, Harbin, Heilongjiang, China.

出版信息

Virulence. 2019 Dec;10(1):58-67. doi: 10.1080/21505594.2018.1557505.

DOI:10.1080/21505594.2018.1557505
PMID:31874073
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6363075/
Abstract

is an important zoonotic pathogen. The massive use of tylosin and other antibiotics in swine production has led to the emergence of resistant phenotypes of . However, there are no adequate measures available to address the problem of bacterial resistance. This study involved the use of 1/4 MIC (0.125 µg/mL) of tylosin to investigate resistance-related proteins by ATCC 700794. Our results showed that 171 proteins were differentially expressed in tested with 1/4 MIC (0.125 µg/mL) of tylosin using iTRAQ-based quantitative proteomic methods. TCS, heat shock protein and elongation factors were differentially expressed at 1/4 MIC (0.125 µg/mL) of tylosin compared to non treated, control cells. Using quantitative RT-PCR analysis, we verified the relationship between the differentially expressed proteins in with different MIC values. The data showed that expression profile for elongation factor G (), elongation factor Ts (), elongation factor Tu (), putative histidine kinase of the competence regulon, ComD (), putative competence-damage inducible protein () and protein GrpE (), observed in tylosin-resistant , correlated with that of ATCC 700794 at 1/4 MIC (0.125 µg/mL). The MIC of tylosin-resistant showed high-level resistance in terramycin, chlortetracycline, ofloxacin and enrofloxacin. Our findings demonstrated the importance of elongation factors, TCS and heat shock protein during development of tylosin resistance in . Thus, our study will provide insight into new drug targets and help reduce bacterial multidrug resistance through development of corresponding inhibitors.

摘要

是一种重要的人畜共患病病原体。泰乐菌素和其他抗生素在猪生产中的大量使用导致了 耐药表型的出现。然而,目前还没有足够的措施来解决细菌耐药性的问题。本研究使用 1/4 MIC(0.125 µg/mL)的泰乐菌素来研究 ATCC 700794 中的耐药相关蛋白。我们的结果表明,使用 iTRAQ 定量蛋白质组学方法,用 1/4 MIC(0.125 µg/mL)的泰乐菌素处理时,有 171 种蛋白质在 中表达差异。与未处理的对照细胞相比,TCS、热休克蛋白和延伸因子在 1/4 MIC(0.125 µg/mL)的泰乐菌素下表达差异。通过定量 RT-PCR 分析,我们验证了不同 MIC 值下 中差异表达蛋白之间的关系。数据表明,在泰乐菌素耐药 中观察到的延伸因子 G()、延伸因子 Ts()、延伸因子 Tu()、假定的感受态调节子组氨酸激酶 ComD()、假定的感受态损伤诱导蛋白()和 GrpE 蛋白()的表达谱与 ATCC 700794 在 1/4 MIC(0.125 µg/mL)下的表达谱相关。泰乐菌素耐药株对土霉素、金霉素、氧氟沙星和恩诺沙星的 MIC 呈高水平耐药。我们的研究结果表明,在 中泰乐菌素耐药性的发展过程中,延伸因子、TCS 和热休克蛋白非常重要。因此,我们的研究将为新的药物靶点提供见解,并通过开发相应的抑制剂帮助减少细菌的多药耐药性。

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