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首页> 外文期刊>The Journal of Antibiotics: An International Journal >High-throughput identification of the sensitivities of an Escherichia coli Delta recA mutant strain to various chemical compounds
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High-throughput identification of the sensitivities of an Escherichia coli Delta recA mutant strain to various chemical compounds

机译:对各种化合物对大肠杆菌δ突变体菌株的敏感性的高通量鉴定

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摘要

Antibiotic resistance is considered a global threat to public health. Adaptive resistance mutations and the acquisition of resistance genes by horizontal gene transfer are known to be facilitated by the RecA-dependent SOS response during antibiotic treatment, making RecA inhibitors promising agents for the prevention of antibiotic resistance. However, the impact of RecA inactivation on antibiotic sensitivities remains unclear. Therefore, in this study, we performed high-throughput screening to determine the minimum inhibitory concentrations (MICs) of 217 chemicals, including both antibiotics and toxic chemicals of unknown drug action, in the wild-type MDS42 and the Delta recA mutant strains of Escherichia coli. The Delta recA mutant showed increased sensitivity to DNA-damaging agents, DNA replication inhibitors, and chromate stress, as well as to other chemicals, such as S-(2-aminoethyl)-L-cysteine, L-histidine, ruthenium red, D-penicillamine, carbonyl cyanide 3-chlorophenylhydrazone (CCCP), cerulenin, and L-cysteine. Microarray analysis showed further that the Delta recA mutant had lower expressions of glnK, nac, and glnLG, which encode nitrogen assimilation regulators, as well as amtB, which encodes an ammonium transporter, compared with the wild type. These findings suggest that the Delta recA mutation affects not only the SOS response but also amino acid metabolism.
机译:抗生素抗性被认为是对公共卫生的全球威胁。通过抗生素治疗期间的RECA依赖性SOS反应促进了自适应电阻突变和通过水平基因转移获取抗性基因,使RECA抑制剂预防抗生素抗性的有前途的药剂。然而,RECA失活对抗生素敏感性的影响仍不清楚。因此,在本研究中,我们进行了高通量筛选,以确定217种化学物质的最小抑制浓度(MIC),包括未知药物作用的抗生素和有毒化学物质,在野生型MDS42和大肠杆菌均突变体突变株中大肠杆菌。 Delta RECA突变体表明对DNA损伤剂,DNA复制抑制剂和铬酸盐胁迫以及其他化学物质的敏感性增加,以及其他化学物质,例如S-(2-氨基乙基)-L-半胱氨酸,L-组氨酸,钌红,D -Penicillamine,羰基氰化物3-氯苯基腙(CCCP),CERULENIN和L-半胱氨酸。微阵列分析进一步表明,Delta Rega突变体具有较低的GlNK,NAC和GLNLG,其编码氮同化调节剂以及编码铵转运蛋白的AMTB,与野生型相比。这些发现表明,Delta RECA突变不仅影响SOS反应,还会影响氨基酸代谢。

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