Clinical Microbiology Research Center, Ilam University of Medical Sciences, Ilam, Iran.
Department of Medical Microbiology and Parasitology, Faculty of Medicine and Health sciences, Universiti Putra Malaysia, Serdang, Malaysia.
Curr Pharm Des. 2018;24(11):1204-1210. doi: 10.2174/1381612824666171213094730.
Neisseria meningitidis is considered as a dangerous pathogen threatening human health. Nowadays, the new drug target is focused. Toxin antitoxin (TA) system is recently identified as an antimicrobial drug target. Also, in N. meningitidis, iron-uptake system could be an interesting target for drug discovery.
In this study, fbpA and mazE genes were chosen as new antimicrobial targets and treated with antisense peptide nucleic acid (PNA). Firstly, they were evaluated by bioinformatics and then analyzed by experimental procedures. Secondly, the functionality was evaluated by stress conditions.
Our results interestingly demonstrated that when fbpA and mazE loci of N. meningitidis were targeted by antisense PNA, 8 µM concentration of fbpA-PNA as well as 30 µM concentration of mazE-PNA inhibited the growth of N. meningitides and were found to be bacteriostatic, whereas 10 μM concentration of fbpA-PNA showed bacteriocidal activity.
Our findings demonstrated the bactriocidal activity of fbpA-PNA and bacteriostatic activity of mazEPNA. Therefore, mazE and fbpA genes should be potent antimicrobial targets but further analysis including in vivo analysis should be performed.
脑膜炎奈瑟菌被认为是威胁人类健康的危险病原体。如今，新的药物靶点是聚焦的。毒素-抗毒素（TA）系统最近被确定为一种抗菌药物靶点。此外，在脑膜炎奈瑟菌中，铁摄取系统可能是药物发现的一个有趣靶点。
在这项研究中，fbpA 和 mazE 基因被选为新的抗菌靶标，并使用反义肽核酸（PNA）进行处理。首先，通过生物信息学进行评估，然后通过实验程序进行分析。其次，通过应激条件评估功能。
我们的结果有趣地表明，当脑膜炎奈瑟菌的 fbpA 和 mazE 基因座被反义 PNA 靶向时，8µM 浓度的 fbpA-PNA 以及 30µM 浓度的 mazE-PNA 抑制了脑膜炎奈瑟菌的生长，被发现具有抑菌作用，而 10µM 浓度的 fbpA-PNA 则表现出杀菌活性。
我们的研究结果表明，fbpA-PNA 具有杀菌活性，mazE-PNA 具有抑菌活性。因此，mazE 和 fbpA 基因应该是潜在的抗菌靶点，但需要进一步包括体内分析在内的分析。
