Adnan Mohd, Siddiqui Arif Jamal, Noumi Emira, Hannachi Sami, Ashraf Syed Amir, Awadelkareem Amir Mahgoub, Snoussi Mejdi, Badraoui Riadh, Bardakci Fevzi, Sachidanandan Manojkumar, Patel Mirav, Patel Mitesh
Department of Biology, College of Science, University of Hail, Hail P.O. Box 2440, Saudi Arabia.
Department of Clinical Nutrition, College of Applied Medial Sciences, University of Hail, Hail P.O. Box 2440, Saudi Arabia.
Antibiotics (Basel). 2022 Dec 20;12(1):5. doi: 10.3390/antibiotics12010005.
() is a serious food-borne pathogen that can cause listeriosis, an illness caused by eating food contaminated with this pathogen. Currently, the treatment or prevention of listeriosis is a global challenge due to the resistance of bacteria against multiple commonly used antibiotics, thus necessitating the development of novel green antimicrobials. Scientists are increasingly interested in microbial surfactants, commonly known as "biosurfactants", due to their antimicrobial properties and eco-friendly nature, which make them an ideal candidate to combat a variety of bacterial infections. Therefore, the present study was designed to use a network pharmacology approach to uncover the active biosurfactants and their potential targets, as well as the signaling pathway(s) involved in listeriosis treatment. In the framework of this study, 15 biosurfactants were screened out for subsequent studies. Among 546 putative targets of biosurfactants and 244 targets of disease, 37 targets were identified as potential targets for treatment of infection, and these 37 targets were significantly enriched in a Gene Ontology (GO) analysis, which aims to identify those biological processes, cellular locations, and molecular functions that are impacted in the condition studied. The obtained results revealed several important biological processes, such as positive regulation of MAP kinase activity, protein kinase B signaling, ERK1 and ERK2 cascade, ERBB signaling pathway, positive regulation of protein serine/threonine kinase activity, and regulation of caveolin-mediated endocytosis. Several important KEGG pathways, such as the ERBBB signaling pathway, TH17 cell differentiation, HIF-1 signaling pathway, infection, Shigellosis, and C-type lectin receptor signaling pathways, were identified. The protein-protein interaction analysis yielded 10 core targets (IL2, MAPK1, EGFR, PTPRC, TNF, ITGB1, IL1B, ERBB2, SRC, and mTOR). Molecular docking was used in the latter part of the study to verify the effectiveness of the active biosurfactants against the potential targets. Lastly, we found that a few highly active biosurfactants, namely lichenysin, iturin, surfactin, rhamnolipid, subtilisin, and polymyxin, had high binding affinities towards IL2, MAPK1, EGFR, PTPRC, TNF, ITGB1, IL1B, ERBB2, SRC, and mTOR, which may act as potential therapeutic targets for listeriosis. Overall, based on the integrated network pharmacology and docking analysis, we found that biosurfactants possess promising anti-listeriosis properties and explored the pharmacological mechanisms behind their effect, laying the groundwork for further research and development.
（某病原体）是一种严重的食源性病原体，可导致李斯特菌病，即因食用被该病原体污染的食物而引发的疾病。目前，由于细菌对多种常用抗生素产生耐药性，李斯特菌病的治疗或预防成为一项全球性挑战，因此有必要开发新型绿色抗菌剂。科学家们对微生物表面活性剂（通常称为“生物表面活性剂”）越来越感兴趣，因为它们具有抗菌特性且对环境友好，这使其成为对抗多种细菌感染的理想候选物。因此，本研究旨在采用网络药理学方法来揭示活性生物表面活性剂及其潜在靶点，以及参与李斯特菌病治疗的信号通路。在本研究框架内，筛选出15种生物表面活性剂用于后续研究。在生物表面活性剂的546个假定靶点和疾病的244个靶点中，37个靶点被确定为治疗（该病原体）感染的潜在靶点，并且在基因本体（GO）分析中这些37个靶点显著富集，该分析旨在识别在所研究病症中受到影响的那些生物学过程、细胞位置和分子功能。所得结果揭示了几个重要的生物学过程，如丝裂原活化蛋白激酶活性的正调控、蛋白激酶B信号传导、ERK1和ERK2级联反应、ERBB信号通路、蛋白丝氨酸/苏氨酸激酶活性的正调控以及小窝蛋白介导的内吞作用的调控。还确定了几个重要的京都基因与基因组百科全书（KEGG）通路，如ERBBB信号通路、TH17细胞分化、低氧诱导因子 - 1信号通路、（该病原体）感染、志贺菌病和C型凝集素受体信号通路。蛋白质 - 蛋白质相互作用分析产生了10个核心靶点（白细胞介素2、丝裂原活化蛋白激酶1、表皮生长因子受体、蛋白酪氨酸磷酸酶受体C、肿瘤坏死因子、整合素β1、白细胞介素1β、ERBB2、原癌基因酪氨酸蛋白激酶SRC和雷帕霉素靶蛋白）。在研究的后半部分使用分子对接来验证活性生物表面活性剂对潜在靶点的有效性。最后，我们发现一些高活性生物表面活性剂，即地衣溶素、伊枯草菌素、表面活性素、鼠李糖脂、枯草杆菌蛋白酶和多粘菌素，对白细胞介素2、丝裂原活化蛋白激酶1、表皮生长因子受体、蛋白酪氨酸磷酸酶受体C、肿瘤坏死因子、整合素β1、白细胞介素1β、ERBB2、原癌基因酪氨酸蛋白激酶SRC和雷帕霉素靶蛋白具有高结合亲和力，这些可能作为李斯特菌病的潜在治疗靶点。总体而言，基于综合的网络药理学和对接分析，我们发现生物表面活性剂具有有前景的抗李斯特菌病特性，并探索了其作用背后的药理机制，为进一步的研发奠定了基础。
