Boakye Aaron, Seidu Muntawakilu Padiga, Adomako Alice, Laryea Michael Konney, Borquaye Lawrence Sheringham
Department of Chemistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
Central Laboratory, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
Bioinform Biol Insights. 2024 Sep 5;18:11779322241275843. doi: 10.1177/11779322241275843. eCollection 2024.
The quorum-sensing (QS) machinery in disease-causing microorganisms is critical in developing antibiotic resistance. In , QS is involved in biofilm formation, virulence factors production, and general tolerance to antimicrobials. Owing to the major role QS plays, interference in the process is probably a facile route to overcome antimicrobial resistance. Some furanone-derived compounds from marine sources have shown promising anti-QS activity. However, their protein targets and potential mechanisms of action have not been explored. To elucidate their potential protein targets in this study, marine metabolites with furanone backbones similar to their cognitive autoinducers (AIs) were screened against various QS receptors (LasR, RhlR, and PqsR) using molecular docking and molecular dynamics (MD) simulation techniques. The order by which the compounds bind to the receptors follows LasR > RhlR > PqsR. Compounds exhibited remarkable stability against LasR and RhlR, likely because the AIs of these receptors are structural analogs of furanones. Furanones with shorter alkyl side chains bound strongly against RhlR. The presence of halogens improved binding against various receptors. PqsR, with its hydrophobic-binding site and structurally different AIs, showed weaker binding. This study provides a molecular basis for the design of potent antagonists against QS receptors using marine-derived furanones.
致病微生物中的群体感应（QS）机制在产生抗生素耐药性方面至关重要。在[具体情况未提及处]，QS参与生物膜形成、毒力因子产生以及对抗菌剂的总体耐受性。由于QS发挥的主要作用，干扰该过程可能是克服抗菌耐药性的一条简便途径。一些来自海洋来源的呋喃酮衍生化合物已显示出有前景的抗QS活性。然而，它们的蛋白质靶点和潜在作用机制尚未得到探索。为了在本研究中阐明它们潜在的蛋白质靶点，使用分子对接和分子动力学（MD）模拟技术，针对各种QS受体（LasR、RhlR和PqsR）筛选了具有与其已知自诱导物（AIs）相似呋喃酮骨架的海洋代谢物。化合物与受体结合的顺序为LasR > RhlR > PqsR。化合物对LasR和RhlR表现出显著的稳定性，可能是因为这些受体的AIs是呋喃酮的结构类似物。具有较短烷基侧链的呋喃酮与RhlR的结合力很强。卤素的存在改善了对各种受体的结合。PqsR因其疏水结合位点和结构不同的AIs，表现出较弱的结合。本研究为使用海洋来源的呋喃酮设计针对QS受体的有效拮抗剂提供了分子基础。
