Koosehlar Eman, Mohabatkar Hassan, Behbahani Mandana
Department of Biotechnology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan 81746-73441, Iran.
Int J Mol Cell Med. 2024;13(1):46-63. doi: 10.22088/IJMCM.BUMS.13.1.46.
One of the burning issues facing healthcare organizations is multidrug-resistant (MDR) bacteria. is an MDR opportunistic bacterium responsible for nosocomial and fatal infections in immunosuppressed individuals. According to previous studies, efflux pump activity and biofilm formation are the most common resistance mechanisms in . The aim of this study was to propose new antimicrobial peptides (AMPs) that target and can effectively address these resistance mechanisms through and assessments. Since AMPs are an attractive alternative to antibiotics, in vitro experiments were carried out along with bioinformatics analyses on 19 Nef peptides (derived from the HIV-1 Nef protein) in the current study. Several servers, including Dbaasps, Antibp2, CLASSAMP2, ToxinPred, dPABBs and ProtParam were used to predict Nef peptides as AMPs. To evaluate the binding affinities, a molecular docking analysis was performed with the HADDOCK web server for all Nef peptide models against two effective proteins of (MexB and PqsR) that play a role in efflux and quorum sensing. Moreover, the antibacterial and antibiofilm activity of the Nef peptides was investigated in a resistant strain of . The results of molecular docking revealed that all Nef peptides have a significant binding affinity to the abovementioned proteins. Nef-Peptide-19 has the highest affinity to the active sites of MexB and PqsR with the HADDOCK scores of -136.1 ± 1.7 and -129.4 ± 2, respectively. According to the results of evaluation, Nef peptide 19 showed remarked activity against with minimum inhibitory and bactericidal concen-trations (MIC and MBC) of 10 µM and 20 µM, respectively. In addition, biofilm inhibitory activity was observed at a concentration of 20 µM. Finally, Nef peptide 19 is proposed as a new AMP against .
医疗保健机构面临的紧迫问题之一是多重耐药（MDR）细菌。[具体细菌名称]是一种多重耐药的机会致病菌，可导致免疫功能低下个体发生医院感染和致命感染。根据以往研究，外排泵活性和生物膜形成是[具体细菌名称]中最常见的耐药机制。本研究的目的是提出针对[具体细菌名称]的新型抗菌肽（AMP），并通过[具体实验方法1]和[具体实验方法2]评估有效地解决这些耐药机制。由于抗菌肽是抗生素的一种有吸引力的替代品，因此在本研究中对19种Nef肽（源自HIV-1 Nef蛋白）进行了体外实验以及生物信息学分析。使用了包括Dbaasps、Antibp2、CLASSAMP2、ToxinPred、dPABBs和ProtParam在内的多个服务器来预测Nef肽为抗菌肽。为了评估结合亲和力，使用HADDOCK网络服务器对所有Nef肽模型与[具体细菌名称]的两种有效蛋白（MexB和PqsR）进行分子对接分析，这两种蛋白在物质外排和群体感应中起作用。此外，还在[具体细菌名称]的耐药菌株中研究了Nef肽的抗菌和抗生物膜活性。分子对接结果表明，所有Nef肽与上述蛋白均具有显著的结合亲和力。Nef-肽-19对MexB和PqsR的活性位点具有最高亲和力，HADDOCK评分分别为-136.1±1.7和-129.4±2。根据[具体评估结果]，Nef肽19对[具体细菌名称]表现出显著活性，最小抑菌浓度（MIC）和最小杀菌浓度（MBC）分别为10μM和20μM。此外，在20μM浓度下观察到生物膜抑制活性。最后，提出Nef肽19作为一种针对[具体细菌名称]的新型抗菌肽。
