化脓性链球菌
益生菌
抗生素
微生物学
体内
病菌
生物
离体
唾液链球菌
抗菌剂
殖民地化
链球菌
细菌
生物技术
遗传学
金黄色葡萄球菌
作者
Hackwon Do,Zhongrui Li,Praveen Kumar Tripathi,Suparna Mitra,Stephanie Guerra,Ananya Dash,Dulanthi Weerasekera,Nishanth Makthal,Saeed Shams,Shifu Aggarwal,Bharat Bhushan Singh,Di Gu,Yongle Du,Randall J. Olsen,Christopher N. LaRock,Wenjun Zhang,Muthiah Kumaraswami
出处
期刊:Nature microbiology
日期:2024-01-16
标识
DOI:10.1038/s41564-023-01583-9
摘要
Abstract Probiotic supplements are suggested to promote human health by preventing pathogen colonization. However, the mechanistic bases for their efficacy in vivo are largely uncharacterized. Here using metabolomics and bacterial genetics, we show that the human oral probiotic Streptococcus salivarius K12 (SAL) produces salivabactin, an antibiotic that effectively inhibits pathogenic Streptococcus pyogenes (GAS) in vitro and in mice. However, prophylactic dosing with SAL enhanced GAS colonization in mice and ex vivo in human saliva. We showed that, on co-colonization, GAS responds to a SAL intercellular peptide signal that controls SAL salivabactin production. GAS produces a secreted protease, SpeB, that targets SAL-derived salivaricins and enhances GAS survival. Using this knowledge, we re-engineered probiotic SAL to prevent signal eavesdropping by GAS and potentiate SAL antimicrobials. This engineered probiotic demonstrated superior efficacy in preventing GAS colonization in vivo. Our findings show that knowledge of interspecies interactions can identify antibiotic- and probiotic-based strategies to combat infection.
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