吲哚可能有助于头孢他啶亚抑制浓度胁迫下大肠杆菌抗生素耐药基因的水平传播

IF 2.6 2区 生物学 Q3 CELL BIOLOGY
Weiqi Dong, Panpan Du, Ruisen Huang, Shuoyan Lv, Hong Chen, Songlei Guan
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引用次数: 0

摘要

目的:环境中抗生素的亚抑制浓度是抗生素耐药基因(ARGs)水平传播的一个重要风险因素。耐药基因传播的信号机制尚不清楚。本研究旨在探讨在亚抑制浓度抗生素的压力下,吲哚能否作为一种分子信号来帮助ARGs的传播:方法:通过共轭试验研究吲哚对共轭频率的影响,并观察其对大肠杆菌Ⅳ型分泌系统和纤毛基因表达的影响。同时,我们还研究了吲哚调控因子ibpA、tnaA和浓度泵的变化趋势。随后,我们预测了与吲哚特异性结合的受体。最后,我们的研究重点是阐明吲哚合成的调控机制:结果:在 1/5MIC 浓度的头孢他啶压力下,共轭物频率明显增加。转入的 ARG 为 blaCTX-M 和 foxA。移动质粒为 IncY 或 IncI2。同时,内源性吲哚的浓度也显著增加。令人惊讶的是,抑制内源性吲哚的产生会导致共轭频率显著下降。然而,当菌株重新获得外源吲哚时,共轭频率再次增加。此外,吲哚调节因子(ibpA、tnaA)mRNA和浓度泵(acrEF、mtr)mRNA的波动趋势与吲哚的波动趋势一致。随后,我们发现吲哚的受体可能是三氯氢硅的四个靶标:CreC、PhoB、AtoC 和 UhpA。此外,当菌株再次摄取外源吲哚时,T4SS(virB2、virB6和virD4)和pppA(编码纤毛虫前体)基因的mRNA水平显著增加。这表明吲哚与共轭通道之间存在密切关系,而共轭通道是遗传物质水平转移的必要条件。然后,吲哚和 tnaA mRNA 的变化趋势与 ibpA(SOS 反应之一)的变化趋势一致。因此,这一结果证实了在亚抑制浓度的抗生素作用下,吲哚受 SOS 反应的调控:结论:众所周知,亚抑制浓度的抗生素会刺激大肠杆菌的 SOS 反应,从而通过调节吲哚来帮助 ARGs 的水平传播。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Indole May Help the Horizontal Transmission of Antibiotic Resistance Genes in E. coli Under Subinhibitory Concentrations of Cefotaxime Stress

Indole May Help the Horizontal Transmission of Antibiotic Resistance Genes in E. coli Under Subinhibitory Concentrations of Cefotaxime Stress

Objectives: Subinhibitory concentration of antibiotics in the environment is an important risk factor for the horizontal transmission of antibiotic resistance genes (ARGs). The signaling mechanism of resistance gene transmission remains unknown. The aim of this study was to investigate whether indole could be used as a molecular signal to help the spread of ARGs under the stress of subinhibitory concentrations of antibiotics.

Methods: The effect of indole on conjugation frequency was investigated through a conjugation test, and its effect on the Type IV secretion system and pili gene expression of E. coli was observed. Meanwhile, we were investigating the trend of changes in indole regulatory factors ibpA, tnaA, and concentration pumps. Subsequently, we predicted the receptors that specifically bind to indole. Finally, our study focused on elucidating the regulatory mechanism of indole synthesis.

Results: Conjugate frequency was significantly increased under 1/5MIC concentration cefotaxime stress. The transferred ARGs were blaCTX-M and foxA. The mobile plasmid was IncY or IncI2. Meanwhile, the concentration of endogenous indole was also significantly increased. And, surprisingly, inhibition of endogenous indole production resulted in a significant decrease in conjugate frequency. However, the conjugate frequency increased once again when the strains reacquired the exogenous indole. Furthermore, the fluctuation trends of indole-regulated factor (ibpA, tnaA) mRNA and concentration pumps (acrEF, mtr) mRNA consistently with that of indole. Then, we found that the receptors of indole may be four targets of TCSs: CreC, PhoB, AtoC, and UhpA. More than that, when strains retrieved the exogenous indole again, the mRNA levels of T4SS (virB2, virB6, and virD4) and pppA (coding Pili precursor) genes significantly increased. This indicates that there is a close relationship between indole and conjugated channels, which are necessary for horizontal transfer of genetic material. And then, the trends of indole and tnaA mRNA were consistent with that of ibpA (one of SOS response). So, this result confirmed that indole was regulated by SOS response under subinhibitory concentrations of antibiotics.

Conclusions: It is always known that subinhibitory concentrations of antibiotics stimulate an SOS response in E. coli, which helps in the horizontal spread of ARGs by modulating indole.

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来源期刊
Cellular Microbiology
Cellular Microbiology 生物-微生物学
CiteScore
9.70
自引率
0.00%
发文量
26
审稿时长
3 months
期刊介绍: Cellular Microbiology aims to publish outstanding contributions to the understanding of interactions between microbes, prokaryotes and eukaryotes, and their host in the context of pathogenic or mutualistic relationships, including co-infections and microbiota. We welcome studies on single cells, animals and plants, and encourage the use of model hosts and organoid cultures. Submission on cell and molecular biological aspects of microbes, such as their intracellular organization or the establishment and maintenance of their architecture in relation to virulence and pathogenicity are also encouraged. Contributions must provide mechanistic insights supported by quantitative data obtained through imaging, cellular, biochemical, structural or genetic approaches.
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