Biotechnology Application & Research Centre, Bilecik Seyh Edebali University, Bilecik, Turkey.
Department of Molecular Biology and Genetics, Bilecik Seyh Edebali University, Bilecik, Turkey.
Appl Microbiol Biotechnol. 2024 Dec;108(1):5. doi: 10.1007/s00253-023-12929-y. Epub 2024 Jan 2.
Antibiotic resistance is an important problem that threatens medical treatment. Differences in the resistance levels of microorganisms cause great difficulties in understanding the mechanisms of antibiotic resistance. Therefore, the molecular reasons underlying the differences in the level of antibiotic resistance need to be clarified. For this purpose, genomic and transcriptomic analyses were performed on three Escherichia coli strains with varying degrees of adaptive resistance to ampicillin. Whole-genome sequencing of strains with different levels of resistance detected five mutations in strains with 10-fold resistance and two additional mutations in strains with 95-fold resistance. Overall, three of the seven mutations occurred as a single base change, while the other four occurred as insertions or deletions. While it was thought that 10-fold resistance was achieved by the effect of mutations in the ftsI, marAR, and rpoC genes, it was found that 95-fold resistance was achieved by the synergistic effect of five mutations and the ampC mutation. In addition, when the general transcriptomic profiles were examined, it was found that similar transcriptomic responses were elicited in strains with different levels of resistance. This study will improve our view of resistance mechanisms in bacteria with different levels of resistance and provide the basis for our understanding of the molecular mechanism of antibiotic resistance in ampicillin-resistant E. coli strains. KEY POINTS: •The mutation of the ampC promoter may act synergistically with other mutations and lead to higher resistance. •Similar transcriptomic responses to ampicillin are induced in strains with different levels of resistance. •Low antibiotic concentrations are the steps that allow rapid achievement of high antibiotic resistance.
抗生素耐药性是一个威胁医疗的重要问题。微生物耐药水平的差异给理解抗生素耐药机制带来了很大的困难。因此，需要阐明导致抗生素耐药水平差异的分子原因。为此，对三种具有不同氨苄青霉素适应性耐药水平的大肠杆菌菌株进行了基因组和转录组分析。对耐药水平不同的菌株进行全基因组测序，发现 10 倍耐药菌株有 5 个突变，95 倍耐药菌株有 2 个额外突变。总的来说，7 个突变中有 3 个是单个碱基变化，而另外 4 个是插入或缺失。虽然认为 10 倍耐药是由于 ftsI、marAR 和 rpoC 基因突变的影响，但发现 95 倍耐药是由 5 个突变和 ampC 突变的协同作用产生的。此外，当检查一般转录组谱时，发现不同耐药水平的菌株中诱导了相似的转录组反应。这项研究将提高我们对不同耐药水平细菌耐药机制的认识，并为我们理解氨苄青霉素耐药大肠杆菌菌株抗生素耐药的分子机制提供基础。
ampC 启动子的突变可能与其他突变协同作用，导致更高的耐药性。
不同耐药水平的菌株对氨苄青霉素产生相似的转录组反应。
低抗生素浓度是快速获得高抗生素耐药性的步骤。
