PDF(Pubmed)
Abstract：
Multidrug-resistant microorganisms have become a major public health concern around the world. The gut microbiome is a gold mine for bioactive compounds that protect the human body from pathogens. We used a multi-omics approach that integrated whole-genome sequencing (WGS) of 74 commensal gut microbiome isolates with metabolome analysis to discover their metabolic interaction with Salmonella and other antibiotic-resistant pathogens. We evaluated differences in the functional potential of these selected isolates based on WGS annotation profiles. Furthermore, the top altered metabolites in co-culture supernatants of selected commensal gut microbiome isolates were identified including a series of dipeptides and examined for their ability to prevent the growth of various antibiotic-resistant bacteria. Our results provide compelling evidence that the gut microbiome produces metabolites, including the compound class of dipeptides that can potentially be applied for anti-infection medication, especially against antibiotic-resistant pathogens. Our established pipeline for the discovery and validation of bioactive metabolites from the gut microbiome as novel candidates for multidrug-resistant infections represents a new avenue for the discovery of antimicrobial lead structures.
摘要：
多药耐药微生物已成为全世界关注的主要公共卫生问题。肠道微生物组是保护人体免受病原体侵害的生物活性化合物的金矿。我们使用了一种多组学方法，将74个共生肠道微生物组分离株的全基因组测序（WGS）与代谢组分析相结合，以发现它们与沙门氏菌和其他抗生素抗性病原体的代谢相互作用。我们基于WGS注释谱评估了这些选择的分离株的功能潜力的差异。此外，在选定的共生肠道微生物组分离株的共培养上清液中,鉴定出了最多的改变的代谢物,包括一系列二肽,并检查了它们阻止各种抗生素抗性细菌生长的能力.我们的结果提供了令人信服的证据，表明肠道微生物组产生代谢产物，包括可能用于抗感染药物的二肽化合物，尤其是对抗生素耐药的病原体。我们建立的管道用于发现和验证来自肠道微生物组的生物活性代谢物作为多药耐药感染的新候选物，代表了发现抗菌铅结构的新途径。
