Ricci Vito, Attah Victoria, Overton Tim, Grainger David C, Piddock Laura J V
Antimicrobials Research Group, School of Immunity and Infection, College of Medical and Dental Sciences, Institute of Microbiology and Infection, University of Birmingham, Birmingham B15 2TT, UK.
Bioengineering, School of Chemical Engineering, University of Birmingham, Birmingham B15 2TT, UK.
Nucleic Acids Res. 2017 Dec 15;45(22):12798-12807. doi: 10.1093/nar/gkx929.
Carbon Storage Regulator A (CsrA) is an RNA binding protein that acts as a global regulator of diverse genes. Using a combination of genetics and biochemistry we show that CsrA binds directly to the 5' end of the transcript encoding AcrAB. Deletion of csrA or mutagenesis of the CsrA binding sites reduced production of both AcrA and AcrB. Nucleotide substitutions at the 5' UTR of acrA mRNA that could potentially weaken the inhibitory RNA secondary structure, allow for more efficient translation of the AcrAB proteins. Given the role of AcrAB-TolC in multi-drug efflux we suggest that CsrA is a potential drug target.
碳储存调节因子A(CsrA)是一种RNA结合蛋白,作为多种基因的全局调节因子。通过遗传学和生物化学相结合的方法,我们发现CsrA直接与编码AcrAB的转录本的5'端结合。删除csrA或对CsrA结合位点进行诱变会降低AcrA和AcrB的产量。acrA mRNA的5'UTR处的核苷酸替换可能会削弱抑制性RNA二级结构,从而使AcrAB蛋白的翻译更有效。鉴于AcrAB-TolC在多药外排中的作用,我们认为CsrA是一个潜在的药物靶点。