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

Abstract

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, smpB and ssrA. And the difference in sensitivity between smpB and ssrA was evident. The MIC of smpB was descended significantly than those of wild type and ssrA in M9 medium supplemented with 1 mM adenosine, illustrating that the adenosine metabolism pathway was principally influenced by SmpB. Likewise, the strain ssrA conferred more sensitivity than wild type and smpB in M9 medium supplemented with 1mM guanosine. By overexpressing acrA/acrB, the tolerance to trimethoprim was partially recovered in ssrA. 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.

Purine metabolism regulates Vibrio splendidus persistence associated with protein aggresome formation and intracellular tetracycline efflux

“…Purines are the most abundant metabolic substrates for all organisms, providing essential components for DNA and RNA synthesis and the necessary energy for cell survival and proliferation ( Virgilio and Adinolfi, 2017 ; Yin et al, 2018 ). In addition, the inhibition of purine metabolism has been linked to antibiotic resistance in E. coli , Bacillus subtilis , Aeromonas veronii ( Sah et al, 2015 ; Stepanek et al, 2016 ; Wang et al, 2020 ). Bacteria are able to take up ATP and GTP via general porins ( Chaudry et al, 1985 ; Rudel et al, 1996 ; Watanabe et al, 2011 ).…”

Essential role of ascO for virulence of Aeromonas veronii and inducing apoptosis

“…A. veronii is a pathogenic bacterium that affects freshwater and marine aquatic species (Wang et al, 2020). Aquaculture has suffered great economic losses due to infections caused by A. veronii , including ulcerative syndrome, hemorrhagic septicemia, and mass mortality in aquatic animals (Dong et al, 2017).…”

Network-based analysis of virulence factors for uncovering Aeromonas veronii pathogenesis

“…niloticus protein interactions were first searched in the PDB database [65] by BLASTP. Five criteria were considered [66][67][68][69]: (1) the alignment between each interacting protein and the template had ≥30% sequence identity and covered ≥40% of the interacting protein length; (2) the templates of two interacting proteins came from different chains of a protein complex structure in the PDB database and further constituted the template complex; (3) the template complex with resolution below 5 Å was prioritized; (4) X-ray structure as template complex was preferred over NMR structure; (5) average sequence identity of two interacting proteins with the template complex was given priority over average coverage, except when several template complexes had similar sequence identity, in which case the template complex with a higher coverage was preferred. Further, five models for each protein were generated using Modeller [70] based on the template.…”

“…Aeromonas veronii is one of the main pathogenic bacteria that affect aquatic animals in freshwater and seawater [ 1 ]. Infections by A. veronii can result in ulcerative syndrome, hemorrhagic septicaemia and mass mortality in aquatic animals such as Oreochromis niloticus [ 2 ], which leads to great economic losses to aquaculture industry.…”