Department of Bioengineering, Faculty of Engineering and Natural Sciences, Üsküdar University, Istanbul, Türkiye.
Genetics of Prokaryotes, Faculty of Biology and Center for Biotechnology (CeBiTec), Bielefeld University, Bielefeld, Germany.
World J Microbiol Biotechnol. 2024 Jul 29;40(9):285. doi: 10.1007/s11274-024-04090-z.
The accelerated spread of antimicrobial-resistant bacteria has caused a serious health problem and rendered antimicrobial treatments ineffective. Innovative approaches are crucial to overcome the health threat posed by resistant pathogens and prevent the emergence of untreatable infections. Triggering stress responses in bacteria can diminish susceptibility to various antimicrobials by inducing resistance mechanisms. Therefore, a thorough understanding of stress response control, especially in relation to antimicrobial resistance, offers valuable perspectives for innovative and efficient therapeutic approaches to combat antimicrobial resistance. The aim of this study was to evaluate the stress responses of 8 different bacteria by analyzing reporter metabolites, around which significant alterations were observed, using a pathway-driven computational approach. For this purpose, the transcriptomic data that the bacterial pathogens were grown under 11 different stress conditions mimicking the human host environments were integrated with the genome-scale metabolic models of 8 pathogenic species (Enterococcus faecalis OG1R, Escherichia coli EPEC O127:H6 E2348/69, Escherichia coli ETEC H10407, Escherichia coli UPEC 536, Klebsiella pneumoniae MGH 78578, Pseudomonas aeruginosa PAO1, Staphylococcus aureus MRSA252, and Staphylococcus aureus MSSA476). The resulting reporter metabolites were enriched in multiple metabolic pathways, with cofactor biosynthesis being the most important. The results of this study will serve as a guide for the development of antimicrobial agents as they provide a first insight into potential drug targets.
抗菌药物耐药菌的加速传播造成了严重的健康问题，使抗菌药物治疗无效。创新方法对于克服耐药病原体带来的健康威胁和防止无法治疗的感染至关重要。在细菌中引发应激反应可以通过诱导耐药机制来降低对各种抗菌药物的敏感性。因此，深入了解应激反应控制，特别是与抗菌药物耐药性相关的应激反应控制，为对抗抗菌药物耐药性提供了有价值的创新和有效的治疗方法的视角。本研究的目的是通过分析报告代谢物来评估 8 种不同细菌的应激反应，在使用基于途径的计算方法时，观察到报告代谢物周围有显著的变化。为此，将模拟人类宿主环境的 11 种不同应激条件下生长的细菌病原体的转录组数据与 8 种病原体物种的基因组规模代谢模型（粪肠球菌 OG1R、大肠杆菌 EPEC O127：H6 E2348/69、大肠杆菌 ETEC H10407、大肠杆菌 UPEC 536、肺炎克雷伯菌 MGH 78578、铜绿假单胞菌 PAO1、金黄色葡萄球菌 MRSA252 和金黄色葡萄球菌 MSSA476）进行了整合。由此产生的报告代谢物在多个代谢途径中富集，其中辅酶生物合成最为重要。本研究的结果将为抗菌药物的开发提供指导，因为它们为潜在的药物靶点提供了初步的见解。
