Parthasarathy Anutthaman, Miranda Renata Rezende, Bedore T J, Watts Lizabeth M, Mantravadi Pavan K, Wong Narayan H, Chu Jonathan, Adjei Joseph A, Rana Amisha P, Savka Michael A, Bulman Zackery P, Borrego Eli J, Hudson André O
School of Chemistry and Biosciences, University of Bradford, Bradford, United Kingdom.
School of Chemistry and Materials Science, Rochester Institute of Technology, Rochester, NY, United States.
Front Pharmacol. 2024 Aug 1;15:1456027. doi: 10.3389/fphar.2024.1456027. eCollection 2024.
Antimicrobial resistance (AMR) is one of the most alarming global public health challenges of the 21st century. Over 3 million antimicrobial-resistant infections occur in the United States annually, with nearly 50,000 cases being fatal. Innovations in drug discovery methods and platforms are crucial to identify novel antibiotics to combat AMR. We present the isolation and characterization of potentially novel antibiotic lead compounds produced by the cross-feeding of two rhizosphere bacteria, sp. RIT 592 and sp. RIT 594. We used solid-phase extraction (SPE) followed by liquid chromatography (LC) to enrich antibiotic extracts and subsequently mass spectrometry (MS) analysis of collected fractions for compound structure identification and characterization. The MS data were processed through the Global Natural Product Social Molecular Networking (GNPS) database. The supernatant from RIT 592 induced RIT 594 to produce a cocktail of antimicrobial compounds active against Gram-positive and negative bacteria. The GNPS analysis indicated compounds with known antimicrobial activity in the bioactive samples, including oligopeptides and their derivatives. This work emphasizes the utility of microbial community-based platforms to discover novel clinically relevant secondary metabolites. Future work includes further structural characterization and antibiotic activity evaluation of the individual compounds against pathogenic multidrug-resistant (MDR) bacteria.
抗菌耐药性(AMR)是21世纪最令人担忧的全球公共卫生挑战之一。美国每年发生超过300万例抗菌药物耐药性感染,其中近5万例是致命的。药物发现方法和平台的创新对于识别对抗AMR的新型抗生素至关重要。我们展示了通过两种根际细菌sp. RIT 592和sp. RIT 594的交叉喂食产生的潜在新型抗生素先导化合物的分离和表征。我们使用固相萃取(SPE),随后进行液相色谱(LC)以富集抗生素提取物,随后对收集的馏分进行质谱(MS)分析以进行化合物结构鉴定和表征。MS数据通过全球天然产物社会分子网络(GNPS)数据库进行处理。来自RIT 592的上清液诱导RIT 594产生对革兰氏阳性和阴性细菌具有活性的抗菌化合物混合物。GNPS分析表明生物活性样品中具有已知抗菌活性的化合物,包括寡肽及其衍生物。这项工作强调了基于微生物群落的平台在发现新型临床相关次级代谢产物方面的实用性。未来的工作包括对单个化合物针对致病性多药耐药(MDR)细菌的进一步结构表征和抗生素活性评估。