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