Mucin O-glycans suppress quorum-sensing pathways and genetic transformation in Streptococcus mutans.
Mucin O-glycans suppress quorum-sensing pathways and genetic transformation in Streptococcus mutans.
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DOI：
10.1038/s41564-021-00876-1
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发表时间：
2021-05
影响因子：
28.3
通讯作者：
Ribbeck K
中科院分区：
文献类型：
--
作者：
Werlang CA;Chen WG;Aoki K;Wheeler KM;Tymm C;Mileti CJ;Burgos AC;Kim K;Tiemeyer M;Ribbeck K
粘液屏障在防止病原体定植的同时容纳了人体内数万亿的微生物。在口腔中，含有粘蛋白MUC5 B和MUC7的唾液形成覆盖软组织和牙齿的薄膜，以防止口腔病原体如变形链球菌感染。唾液粘蛋白可以通过选择性凝集素活性和细菌结合直接与微生物相互作用，但唾液保护功能的程度和基础尚不清楚。使用离体唾液模型，我们确定MUC5B作为微生物毒力的抑制剂。具体而言，我们发现天然纯化的MUC5B下调由感受态刺激肽（CSP）和sigX诱导肽（XIP）激活的群体感应途径的表达。此外，MUC5B通过天然遗传转化防止获得抗微生物剂抗性，这是通过群体感应激活的过程。我们的数据揭示了MUC5B的作用是由其相关的聚糖介导的，这些聚糖是群体感应和遗传转化的有效抑制剂，即使从粘蛋白骨架中去除。总之，这些结果提出粘蛋白聚糖作为驯化潜在致病微生物而不杀死的宿主策略。
Mucus barriers accommodate trillions of microbes throughout the human body while preventing pathogenic colonization. In the oral cavity, saliva containing the mucins MUC5B and MUC7 forms a pellicle that coats the soft tissue and teeth to prevent infection by oral pathogens, such as Streptococcus mutans. Salivary mucin can interact directly with microbes through selective agglutinin activity and bacterial binding, but the extent and basis of saliva’s protective functions are not well understood. Using an ex vivo saliva model, we identify MUC5B as an inhibitor of microbial virulence. Specifically, we find natively purified MUC5B downregulates the expression of quorum sensing pathways activated by the competence stimulating peptide (CSP) and the sigX inducing peptide (XIP). Further, MUC5B prevents the acquisition of antimicrobial resistance through natural genetic transformation, a process activated through quorum sensing. Our data reveal the effect of MUC5B is mediated by its associated glycans, which are potent suppressors of quorum sensing and genetic transformation, even when removed from the mucin backbone. Together, these results present mucin glycans as a host strategy for domesticating potentially pathogenic microbes without killing.
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影响因子：
4
作者：
Hillman, J. D.;Mo, J.;Hillman, C. H.
通讯作者：
Hillman, C. H.
影响因子：
48
作者：
Huber W;Carey VJ;Gentleman R;Anders S;Carlson M;Carvalho BS;Bravo HC;Davis S;Gatto L;Girke T;Gottardo R;Hahne F;Hansen KD;Irizarry RA;Lawrence M;Love MI;MacDonald J;Obenchain V;Oleś AK;Pagès H;Reyes A;Shannon P;Smyth GK;Tenenbaum D;Waldron L;Morgan M
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Morgan M
影响因子：
10.5
作者：
Aframian N;Eldar A
通讯作者：
Eldar A
影响因子：
14.9
作者：
Clark K;Karsch-Mizrachi I;Lipman DJ;Ostell J;Sayers EW
通讯作者：
Sayers EW
影响因子：
3.2
作者：
Dufour, Delphine;Cordova, Martha;Levesque, Celine M.
通讯作者：
Levesque, Celine M.