镧系元素
唾液链球菌
微生物学
微生物群
生物
生物膜
细菌素
唾液乳杆菌
抗菌剂
免疫系统
细菌
免疫学
变形链球菌
生物信息学
乳酸菌
遗传学
作者
Abdelahhad Barbour,Linda L. Smith,Morvarid Oveisi,McKinley Williams,Ruo Chen Huang,Cara Marks,Noah Fine,Cong Sun,Fereshteh Younesi,Sina Zargaran,Ravi S. Orugunty,Thomas D. Horvath,Sigmund J. Haidacher,Anthony M. Haag,Amarpreet Sabharwal,Boris Hinz,Michael Glogauer
标识
DOI:10.1073/pnas.2219392120
摘要
Lantibiotics are ribosomally synthesized and posttranslationally modified peptides (RiPPs) that are produced by bacteria. Interest in this group of natural products is increasing rapidly as alternatives to conventional antibiotics. Some human microbiome–derived commensals produce lantibiotics to impair pathogens’ colonization and promote healthy microbiomes. Streptococcus salivarius is one of the first commensal microbes to colonize the human oral cavity and gastrointestinal tract, and its biosynthesis of RiPPs, called salivaricins, has been shown to inhibit the growth of oral pathogens. Herein, we report on a phosphorylated class of three related RiPPs, collectively referred to as salivaricin 10, that exhibit proimmune activity and targeted antimicrobial properties against known oral pathogens and multispecies biofilms. Strikingly, the immunomodulatory activities observed include upregulation of neutrophil-mediated phagocytosis, promotion of antiinflammatory M2 macrophage polarization, and stimulation of neutrophil chemotaxis—these activities have been attributed to the phosphorylation site identified on the N-terminal region of the peptides. Salivaricin 10 peptides were determined to be produced by S. salivarius strains found in healthy human subjects, and their dual bactericidal/antibiofilm and immunoregulatory activity may provide new means to effectively target infectious pathogens while maintaining important oral microbiota.
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