AUTHOR=Wang Dan , Li Hong , Khan Wasi Ullah , Ma Xiang , Tang Hongqian , Tang Yanqiong , Huang Dongyi , Liu Zhu 

TITLE=SmpB and tmRNA Orchestrate Purine Pathway for the Trimethoprim Resistance in Aeromonas veronii

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2020.00239

DOI=10.3389/fcimb.2020.00239

ISSN=2235-2988

ABSTRACT=<p>Small protein B(SmpB) cooperates with transfer-messenger RNA (tmRNA) for <italic>trans</italic>-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 <italic>smpB</italic> deletion strain than that of wild type, which led to the differential trimethoprim resistance of <italic>Aeromonas veronii</italic> (<italic>A. veronii)</italic>. 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 <italic>ssrA (small stable RNA, tmRNA) deletion strain</italic>, which eventually caused an augmented metabolic product xanthine. In addition, the deletion of <italic>ssrA</italic> also affected the significant downregulations of efflux pump <italic>acrA/acrB</italic>. The minimal inhibitory concentrations (MIC) were overall decreased after the trimethoprim treatment to the wild type, Δ<italic>smpB</italic> and Δ<italic>ssrA</italic>. And the difference in sensitivity between Δ<italic>smpB</italic> and Δ<italic>ssrA</italic> was evident. The MIC of Δ<italic>smpB</italic> was descended significantly than those of wild type and Δ<italic>ssrA</italic> in M9 medium supplemented with 1 mM adenosine, illustrating that the adenosine metabolism pathway was principally influenced by SmpB. Likewise, the strain Δ<italic>ssrA</italic> conferred more sensitivity than wild type and Δ<italic>smpB</italic> in M9 medium supplemented with 1mM guanosine. By overexpressing <italic>acrA</italic>/<italic>acrB</italic>, the tolerance to trimethoprim was partially recovered in Δ<italic>ssrA</italic>. These results revealed that SmpB and tmRNA acted on different branches in purine metabolism, conferring the diverse trimethoprim resistance to <italic>A. veronii</italic>. This study suggests that the <italic>trans</italic>-translation system might be an effective target in clinical treatment of <italic>A. veronii</italic> and other multi-antibiotic resistance bacteria with trimethoprim.</p>