In Silico and In vitro Evaluations of the Antibacterial Activities of HIV-1 Nef Peptides against Pseudomonas aeruginosa.

IF 1.5 Q3 MEDICINE, RESEARCH & EXPERIMENTAL International Journal of Molecular and Cellular Medicine Pub Date : 2024-01-01 DOI:10.22088/IJMCM.BUMS.13.1.46
Eman Koosehlar, Hassan Mohabatkar, Mandana Behbahani
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Abstract

One of the burning issues facing healthcare organizations is multidrug-resistant (MDR) bacteria. P. aeruginosa 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 P. aeruginosa. The aim of this study was to propose new antimicrobial peptides (AMPs) that target P. aeruginosa and can effectively address these resistance mechanisms through in silico and in vitro 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 P. aeruginosa (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 P. aeruginosa. 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 in vitro evaluation, Nef peptide 19 showed remarked activity against P. aeruginosa 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 P. aeruginosa.

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HIV-1 Nef 肽对铜绿假单胞菌抗菌活性的硅学和体外评估。
耐多药(MDR)细菌是医疗机构面临的紧迫问题之一。铜绿假单胞菌(P. aeruginosa)是一种多重耐药机会性细菌,是造成免疫抑制人群院内感染和致命感染的罪魁祸首。根据以往的研究,外排泵活性和生物膜形成是铜绿假单胞菌最常见的耐药机制。本研究旨在通过硅学和体外评估,提出针对铜绿假单胞菌并能有效解决这些耐药机制的新型抗菌肽(AMPs)。由于 AMPs 是抗生素的一种有吸引力的替代品,因此本研究对 19 种 Nef 肽(源自 HIV-1 Nef 蛋白)进行了体外实验和生物信息学分析。包括 Dbaasps、Antibp2、CLASSAMP2、ToxinPred、dPABBs 和 ProtParam 在内的多个服务器被用来预测作为 AMP 的 Nef 肽。为了评估结合亲和力,使用 HADDOCK 网络服务器对所有 Nef 肽模型与铜绿假单胞菌的两种有效蛋白(MexB 和 PqsR)进行了分子对接分析,这两种蛋白在流出和法定量感应中发挥作用。此外,还研究了 Nef 肽在铜绿假单胞菌耐药菌株中的抗菌和抗生物膜活性。分子对接结果表明,所有 Nef 肽都与上述蛋白有显著的结合亲和力。Nef肽-19与MexB和PqsR活性位点的亲和力最高,HADDOCK得分分别为-136.1 ± 1.7和-129.4 ± 2。体外评估结果显示,Nef 肽 19 对铜绿假单胞菌具有显著的活性,最低抑菌浓度(MIC)为 10 µM,最低杀菌浓度(MBC)为 20 µM。此外,在 20 µM 浓度下还观察到了生物膜抑制活性。最后,Nef 肽 19 被认为是一种新的铜绿假单胞菌 AMP。
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期刊介绍: The International Journal of Molecular and Cellular Medicine (IJMCM) is a peer-reviewed, quarterly publication of Cellular and Molecular Biology Research Center (CMBRC), Babol University of Medical Sciences, Babol, Iran. The journal covers all cellular & molecular biology and medicine disciplines such as the genetic basis of disease, biomarker discovery in diagnosis and treatment, genomics and proteomics, bioinformatics, computer applications in human biology, stem cells and tissue engineering, medical biotechnology, nanomedicine, cellular processes related to growth, death and survival, clinical biochemistry, molecular & cellular immunology, molecular and cellular aspects of infectious disease and cancer research. IJMCM is a free access journal. All open access articles published in IJMCM are distributed under the terms of the Creative Commons Attribution CC BY. The journal doesn''t have any submission and article processing charges (APCs).
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