Mingolelli Gabrielle, Raherisoanjato Jessia, Trinh Duong, Gao Yu, Henke Matthew
Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois Chicago, Chicago, Illinois, USA.
mBio. 2025 Jul 17:e0152325. doi: 10.1128/mbio.01523-25.
A diverse, stable community of microbes in the human gut is strongly tied to health. The factors that regulate microbial community structure and dynamics are ill-defined. In this study, we discover mediterrocin, a bacteriocin produced by the core member of the human gut microbiota, (previously ). Following a screen for antimicrobial production by clinical isolates of , mediterrocin was isolated by bioactivity-guided fractionation from strain RJX1121, identified by mass spectrometry, and confirmed by gene disruption. Mediterrocin, an 89 amino acid secreted protein, is a broad-spectrum bacteriocin. Annotation of the mediterrocin biosynthetic gene cluster revealed a wide distribution among Bacillota (previously Firmicutes), including the type strain ATCC249149. The type strain of also produces mediterrocin, but in lower titers than RJX1121 under our culture conditions. Mediterrocin is inhibitory to multiple strains, but with varying sensitivity, with isolates from patients with inflammatory bowel disease displaying the greatest susceptibility. Beyond , mediterrocin demonstrated inhibitory activity against other Lachnospiraceae and the gram-negative pathogen . Further characterization of mediterrocin may clarify how this core member of the healthy microbiome interacts with other community members and how the relative abundance of changes in microbiome dysbiosis associated with several diseases.
is a core member of the gut microbiome and implicated in several diseases. Direct competition between and other members of the microbiome may contribute to the shift from a diverse, structured community to dysbiosis observed in disease. Identifying molecular mechanisms of microbial competition will aid future studies of these disease-relevant bacteria and clarify how community structure is maintained. We report the discovery of mediterrocin, a bacteriocin present in many species in the orders Lachnospirales and Eubacteriales, but clade-specific within . Mediterrocin, produced by health-associated strains of , inhibits the growth of disease-associated strains and a broad spectrum of gut commensal bacteria and pathogens.
人类肠道中多样、稳定的微生物群落与健康密切相关。调节微生物群落结构和动态的因素尚不明确。在本研究中，我们发现了地中海菌素，这是一种由人类肠道微生物群核心成员产生的细菌素（之前 ）。通过对临床分离株的抗菌生产进行筛选后，通过生物活性导向分级分离从菌株RJX1121中分离出地中海菌素，通过质谱鉴定，并通过基因破坏进行确认。地中海菌素是一种89个氨基酸的分泌蛋白，是一种广谱细菌素。地中海菌素生物合成基因簇的注释显示其在芽孢杆菌纲（之前为厚壁菌门）中广泛分布，包括 型菌株ATCC249149。 的型菌株也产生地中海菌素，但在我们的培养条件下，其产量低于RJX1121。地中海菌素对多种 菌株具有抑制作用，但敏感性不同，炎症性肠病患者的分离株显示出最大的敏感性。除了 ，地中海菌素还对其他毛螺菌科和革兰氏阴性病原体 表现出抑制活性。对地中海菌素的进一步表征可能会阐明这种健康微生物群的核心成员如何与其他群落成员相互作用，以及在与几种疾病相关的微生物群失调中 相对丰度如何变化。
是肠道微生物群的核心成员，与多种疾病有关。 与微生物群其他成员之间的直接竞争可能导致从多样、结构化的群落转变为疾病中观察到的失调。确定微生物竞争的分子机制将有助于未来对这些与疾病相关细菌的研究，并阐明群落结构是如何维持的。我们报告了地中海菌素的发现，它存在于毛螺菌目和真杆菌目中的许多物种中，但在 内是特定进化枝的。由与健康相关的 菌株产生的地中海菌素可抑制与疾病相关的 菌株以及多种肠道共生细菌和病原体的生长。
