Quorum Sensing in Streptococcus mutans Regulates Production of Tryglysin, a Novel RaS-RiPP Antimicrobial Compound.
Quorum Sensing in Streptococcus mutans Regulates Production of Tryglysin, a Novel RaS-RiPP Antimicrobial Compound.
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DOI：
10.1128/mbio.02688-20
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发表时间：
2021-03-16
期刊：
影响因子：
6.4
通讯作者：
Federle MJ
中科院分区：
文献类型：
--
作者：
Rued BE;Covington BC;Bushin LB;Szewczyk G;Laczkovich I;Seyedsayamdost MR;Federle MJ
在自然环境中，细菌与大量的生物体相互作用和竞争。变形链球菌就是这样一种微生物，它是口腔微生物群的重要成员。我们发现S.变形链球菌使用群体感应系统来调节能够抑制几种链球菌物种生长的新型后修饰肽的产生。链球菌属包括通常定殖于脊椎动物的粘膜表面的大型细菌分类群，并且能够引起源自不同身体部位（包括呼吸道、消化道和生殖道）的疾病病因。随着抗生素耐药性的升级，确定治疗感染的新模式越来越重要。变形链球菌是一种重要的条件致病菌，是龋齿的病原体，能够引起心内膜炎等全身性疾病。因此，了解它如何调节毒力并在口腔生态位中竞争是制定防御这些病原体的策略的优先事项。我们确定S.变形杆菌UA 159具有真正的短疏水肽（SHP）/Rgg群体感应系统，该系统调节以自由基-SAM（S-腺苷-L-甲硫氨酸）（RaS）酶为特征的专门生物合成操纵子，并产生核糖体合成和后修饰的肽（RiPP）。SHP/Rgg调控系统与RaS生物合成操纵子的配对在链球菌中是保守的，并且存在与S.变形链球菌存在于从野鼠分离的口腔链球菌中。我们从该操纵子中鉴定了RaS-RiPP产物，并使用分析方法的组合解析了其结构;我们将这些RIPP称为Tryglysin A和B，以表示不寻常的Trp-Gly-Lys连接。我们报告说，tryglysins特异性抑制其他链球菌的生长，但不是其他革兰氏阳性菌，如粪肠球菌或乳酸乳球菌。我们预测tryglysin是由S.在其口腔生态位中的变形链球菌，从而抑制竞争物种的生长，包括几种医学相关的链球菌。
Bacteria interact and compete with a large community of organisms in their natural environment. Streptococcus mutans is one such organism, and it is an important member of the oral microbiota. We found that S. mutans uses a quorum-sensing system to regulate production of a novel posttranslationally modified peptide capable of inhibiting growth of several streptococcal species. The genus Streptococcus encompasses a large bacterial taxon that commonly colonizes mucosal surfaces of vertebrates and is capable of disease etiologies originating from diverse body sites, including the respiratory, digestive, and reproductive tracts. Identifying new modes of treating infections is of increasing importance, as antibiotic resistance has escalated. Streptococcus mutans is an important opportunistic pathogen that is an agent of dental caries and is capable of systemic diseases such as endocarditis. As such, understanding how it regulates virulence and competes in the oral niche is a priority in developing strategies to defend from these pathogens. We determined that S. mutans UA159 possesses a bona fide short hydrophobic peptide (SHP)/Rgg quorum-sensing system that regulates a specialized biosynthetic operon featuring a radical-SAM (S-adenosyl-l-methionine) (RaS) enzyme and produces a ribosomally synthesized and posttranslationally modified peptide (RiPP). The pairing of SHP/Rgg regulatory systems with RaS biosynthetic operons is conserved across streptococci, and a locus similar to that in S. mutans is found in Streptococcus ferus, an oral streptococcus isolated from wild rats. We identified the RaS-RiPP product from this operon and solved its structure using a combination of analytical methods; we term these RiPPs tryglysin A and B for the unusual Trp-Gly-Lys linkage. We report that tryglysins specifically inhibit the growth of other streptococci, but not other Gram-positive bacteria such as Enterococcus faecalis or Lactococcus lactis. We predict that tryglysin is produced by S. mutans in its oral niche, thus inhibiting the growth of competing species, including several medically relevant streptococci.