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Mis‐annotations of a promising antibiotic target in high‐priority gram‐negative pathogens

机译:高优先级革兰氏阴性病原体中有前途的抗生素靶标的误报

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The rise of antibiotic resistance combined with the lack of new products entering the market has led to bacterial infections becoming one of the biggest threats to global health. Therefore, there is an urgent need to identify novel antibiotic targets, such as dihydrodipicolinate synthase (DHDPS), an enzyme involved in the production of essential metabolites in cell wall and protein synthesis. Here, we utilised a 7‐residue sequence motif to identify mis‐annotation of multiple DHDPS genes in the high‐priority Gram‐negative bacteria Acinetobacter baumannii and Klebsiella pneumoniae. We subsequently confirmed these mis‐annotations using a combination of enzyme kinetics and X‐ray crystallography. Thus, this study highlights the need to ensure genes encoding promising drug targets, like DHDPS, are annotated correctly, especially for clinically important pathogens.
机译:抗生素抗性的兴起结合进入市场的新产品导致细菌感染成为全球健康的最大威胁之一。因此,迫切需要鉴定新型抗生素靶标,例如二水解喹啉合酶(DHDPS),该酶参与在细胞壁和蛋白质合成中产生的基本代谢物。在此,我们利用了7-残基序列基序来识别高优先级革兰氏阴性细菌在高优先级革兰氏阴性细菌患者Baumannii和Klebsiella肺炎中的MIS-注释。我们随后使用酶动力学和X射线晶体学的组合证实了这些误报。因此,本研究突出了确保编码有前途的药物靶标的基因,如DHDPS,特别适用于临床重要病原体。

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