Small protein B(SmpB) cooperates with transfer-messenger RNA (tmRNA) for trans-translation to ensure the quality control of protein synthesis in prokaryotes. Furthermore, they regulate cell metabolism separately. According to research, SmpB functions as a transcription factor, and tmRNA acts as a small RNA. Purine pathway has been reported to be related to trimethoprim resistance, including hypoxanthine synthesis, adenosine metabolism and guanosine metabolism. Another reason of drug tolerance is the efflux pump of the bacterium. In transcriptomic data, it was shown that the expression of some related enzymes in adenosine metabolism were raised significantly in smpB deletion strain than that of wild type, which led to the differential trimethoprim resistance of Aeromonas veronii (A. veronii). Furthermore, the metabolic products of adenosine AMP, cAMP, and deoxyadenosine were accumulated significantly. However, the expressions of the enzymes related to hypoxanthine synthesis and guanosine metabolism were elevated significantly in ssrA (small stable RNA, tmRNA) deletion strain, which eventually caused an augmented metabolic product xanthine. In addition, the deletion of ssrA also affected the significant downregulations of efflux pump acrA/acrB. The minimal inhibitory concentrations (MIC) were overall decreased after the trimethoprim treatment to the wild type, ΔsmpB and ΔssrA. And the difference in sensitivity between ΔsmpB and ΔssrA was evident. The MIC of ΔsmpB was descended significantly than those of wild type and ΔssrA in M9 medium supplemented with 1 mM adenosine, illustrating that the adenosine metabolism pathway was principally influenced by SmpB. Likewise, the strain ΔssrA conferred more sensitivity than wild type and ΔsmpB in M9 medium supplemented with 1mM guanosine. By overexpressing acrA/acrB, the tolerance to trimethoprim was partially recovered in ΔssrA. These results revealed that SmpB and tmRNA acted on different branches in purine metabolism, conferring the diverse trimethoprim resistance to A. veronii. This study suggests that the trans-translation system might be an effective target in clinical treatment of A. veronii and other multi-antibiotic resistance bacteria with trimethoprim.

中文翻译：

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SmpB 和 tmRNA 协调了维罗单胞菌中甲氧苄啶抗性的嘌呤途径。

小蛋白 B(SmpB) 与转移信使 RNA (tmRNA) 合作进行反式翻译，以确保原核生物中蛋白质合成的质量控制。此外，它们分别调节细胞代谢。根据研究，SmpB 作为转录因子发挥作用，tmRNA 作为小 RNA 发挥作用。据报道，嘌呤途径与甲氧苄啶耐药有关，包括次黄嘌呤合成、腺苷代谢和鸟苷代谢。耐药性的另一个原因是细菌的外排泵。转录组学数据表明，smpB缺失株中腺苷代谢相关酶的表达较野生株显着升高，导致维罗单胞菌（A. veronii）对甲氧苄啶的抗药性差异。此外，腺苷 AMP 的代谢产物，cAMP 和脱氧腺苷显着积累。然而，ssrA（small stable RNA，tmRNA）缺失菌株中次黄嘌呤合成和鸟苷代谢相关酶的表达显着升高，最终导致黄嘌呤代谢产物增加。此外，ssrA的缺失也影响了外排泵acrA/acrB的显着下调。甲氧苄啶处理野生型 ΔsmpB 和 ΔssrA 后，最低抑菌浓度 (MIC) 总体下降。ΔsmpB 和 ΔssrA 之间的灵敏度差异很明显。在补充有 1 mM 腺苷的 M9 培养基中，ΔsmpB 的 MIC 比野生型和 ΔssrA 的 MIC 显着下降，说明腺苷代谢途径主要受 SmpB 影响。同样地，在补充有 1mM 鸟苷的 M9 培养基中，菌株 ΔssrA 比野生型和 ΔsmpB 具有更高的敏感性。通过过度表达 acrA/acrB，对甲氧苄啶的耐受性在 ΔssrA 中部分恢复。这些结果表明，SmpB 和 tmRNA 作用于嘌呤代谢的不同分支，赋予了 A. veronii 不同的甲氧苄啶抗性。该研究表明，反式翻译系统可能是甲氧苄氨嘧啶临床治疗维罗纳曲霉和其他多抗生素耐药菌的有效靶点。赋予 A. veronii 多样的甲氧苄啶抗性。该研究表明，反式翻译系统可能是甲氧苄氨嘧啶临床治疗维罗纳曲霉和其他多抗生素耐药菌的有效靶点。赋予 A. veronii 多种甲氧苄啶抗性。该研究表明，反式翻译系统可能是甲氧苄氨嘧啶临床治疗维罗纳曲霉和其他多抗生素耐药菌的有效靶点。