Tong Chunyu, Liang Yimin, Liu Qi, Yu Honghao, Feng Wenzhi, Song Bocui
College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang, China.
PeerJ. 2024 Nov 29;12:e18572. doi: 10.7717/peerj.18572. eCollection 2024.
Bacteria can develop resistance to various antibiotics under selective pressure, leading to multifaceted changes in resistance mechanisms. Transcriptomic sequencing allows for the observation of transcriptional level alterations in cells under antibiotic stress. Understanding the bacterial response to such stress is essential for deciphering their strategy against drug-resistant antibiotics and identifying potential targets for antibiotic development.
This study using wild-type (WT) () discovered that continuous induction screening for imipenem-resistant strains resulted in bacteria with enhanced biofilm-forming ability and mutations in antibiotic target sites. Transcriptomic sequencing of the resistant bacteria revealed significant changes in carbon and amino acid metabolism, nutrient assimilation, substance transport, nucleotide metabolism, protein biosynthesis, and cell wall biosynthesis. The up-regulated drug efflux genes were disrupted using gene knockout technology. Drug sensitivity tests indicated that drug efflux has a minimal effect on imipenem resistance.
This suggests a strategy for drug resistance involving the reduction of unnecessary substance synthesis and metabolism, coupled with an increase in activities that aid in resisting foreign threats.
在选择性压力下，细菌可对多种抗生素产生耐药性，导致耐药机制发生多方面变化。转录组测序能够观察抗生素应激下细胞转录水平的改变。了解细菌对这种应激的反应对于解读其对抗耐药性抗生素的策略以及确定抗生素开发的潜在靶点至关重要。
本研究使用野生型（WT）（）发现，对亚胺培南耐药菌株进行连续诱导筛选导致细菌生物膜形成能力增强且抗生素靶点位点发生突变。对耐药细菌进行转录组测序发现，碳代谢和氨基酸代谢、营养物质同化、物质转运、核苷酸代谢、蛋白质生物合成以及细胞壁生物合成均发生了显著变化。使用基因敲除技术破坏上调的药物外排基因。药敏试验表明，药物外排对亚胺培南耐药性影响极小。
这提示了一种耐药策略，即减少不必要的物质合成和代谢，同时增加有助于抵御外来威胁的活性。
