Department of Pharmacy and Technology of Organic Substances, Industrial Pharmacy, Ukrainian State Chemical Technology University, Dnipro, Ukraine.
Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
Arch Microbiol. 2024 Feb 23;206(3):117. doi: 10.1007/s00203-024-03849-0.
Campylobacter jejuni is a foodborne pathogen that causes gastroenteritis in humans and has developed resistance to various antibiotics. The primary objective of this research was to examine the network of antibiotic resistance in C. jejuni. The study involved the wild and antibiotic-resistant strains placed in the presence and absence of antibiotics to review their gene expression profiles in response to ciprofloxacin via microarray. Differentially expressed genes (DEGs) analysis and Protein-Protein Interaction (PPI) Network studies were performed for these genes. The results showed that the resistance network of C. jejuni is modular, with different genes involved in bacterial motility, capsule synthesis, efflux, and amino acid and sugar synthesis. Antibiotic treatment resulted in the down-regulation of cluster genes related to translation, flagellum formation, and chemotaxis. In contrast, cluster genes involved in homeostasis, capsule formation, and cation efflux were up-regulated. The study also found that macrolide antibiotics inhibit the progression of C. jejuni infection by inactivating topoisomerase enzymes and increasing the activity of epimerase enzymes, trying to compensate for the effect of DNA twisting. Then, the bacterium limits the movement to conserve energy. Identifying the antibiotic resistance network in C. jejuni can aid in developing drugs to combat these bacteria. Genes involved in cell division, capsule formation, and substance transport may be potential targets for inhibitory drugs. Future research must be directed toward comprehending the underlying mechanisms contributing to the modularity of antibiotic resistance and developing strategies to disrupt and mitigate the growing threat of antibiotic resistance effectively.
空肠弯曲菌是一种食源性病原体，可导致人类肠胃炎，并已对各种抗生素产生耐药性。本研究的主要目的是研究空肠弯曲菌的抗生素耐药网络。该研究涉及野生和抗生素耐药菌株，分别在存在和不存在抗生素的情况下，通过微阵列检测其对环丙沙星的基因表达谱。对这些基因进行差异表达基因（DEG）分析和蛋白质-蛋白质相互作用（PPI）网络研究。结果表明，空肠弯曲菌的耐药网络具有模块性，不同基因参与细菌运动、荚膜合成、外排以及氨基酸和糖合成。抗生素治疗导致与翻译、鞭毛形成和趋化性相关的簇基因下调。相比之下，与内稳性、荚膜形成和阳离子外排相关的簇基因上调。该研究还发现，大环内酯类抗生素通过使拓扑异构酶失活和增加差向异构酶的活性来抑制空肠弯曲菌感染的进展，试图补偿 DNA 扭曲的影响。然后，细菌限制运动以节省能量。鉴定空肠弯曲菌中的抗生素耐药网络有助于开发对抗这些细菌的药物。与细胞分裂、荚膜形成和物质转运相关的基因可能是抑制药物的潜在靶点。未来的研究必须致力于理解抗生素耐药性模块化的潜在机制，并开发有效破坏和减轻抗生素耐药性日益增长威胁的策略。
