Recognition of specific sialoglycan structures by oral streptococci impacts the severity of endocardial infection
Recognition of specific sialoglycan structures by oral streptococci impacts the severity of endocardial infection
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DOI：
10.1371/journal.ppat.1007896
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发表时间：
2019-06-01
期刊：
影响因子：
6.7
通讯作者：
Sullam, Paul M.
中科院分区：
文献类型：
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作者：
Bensing, Barbara A.;Li, Liang;Sullam, Paul M.
戈登链球菌和血链球菌是牙齿表面的主要定植者。虽然在口腔环境中通常无致病性，但它们是感染性心内膜炎的常见原因。两种链球菌都表达富含丝氨酸的重复表面粘附素，其介导粘蛋白样糖蛋白上的唾液酸化聚糖的附着，但识别的特定唾液酸聚糖结构可以因菌株而异。先前的研究表明唾液酸聚糖结合在由某些链球菌引起的主动脉瓣感染中明显重要。gordonii，但这一过程并不有助于一株S.吸血鬼然而，这些链球菌可以结合唾液酸聚糖结构的不同子集。在这里，我们产生了S. gordonii的不同之处仅在于它们所粘附的唾液酸聚糖结构的类型和范围，并检查这是否使它们在大鼠心内膜炎模型中具有更强或更弱的毒性。这些发现表明，识别特定的唾液酸聚糖可以增强或减弱致病性。与唾液酸乳糖胺的结合减少了机械损伤的主动脉瓣的初始定植，而与密切相关的三糖唾液酸T抗原的结合促进了72小时后瓣膜组织中更高的细菌密度。一个令人惊讶的发现是，链球菌与主动脉瓣的初始附着与每种菌株对血小板的亲和力成反比，这表明与血液中循环的血小板结合可能会使细菌远离内膜表面。重要的是，我们发现人和大鼠血小板GPIb α（S. gordonii和S.血小板上的血细胞）显示出相似的O-聚糖结构，主要由二唾液酸化的核心2六糖组成，尽管大鼠GPIb α具有更异质的修饰唾液酸组成。综合结果表明，链球菌与GPIb α上的次要O-聚糖的相互作用可能比GPIb α对致病作用的总体亲和力更重要。作者摘要感染性心内膜炎（IE）是一种危及生命的心脏瓣膜感染，通常存在于口腔中的链球菌是这种疾病的主要原因。一些口腔链球菌物种在其表面上表达一种蛋白质，该蛋白质能够附着到唾液蛋白上的聚糖（糖）修饰，这种相互作用对于牙齿和其他口腔表面的定植可能是重要的。这些“Siglec样粘附素”在它们结合的聚糖结构的类型和数量上是高度可变的，范围从唾液蛋白上显示的结构中的仅一个到多于六个。如果链球菌进入血液，Siglec样粘附素可以介导与修饰血小板或血浆蛋白的类似聚糖的附着，这可以影响生物体的整体毒力。这项研究强调了识别特定类型的聚糖结构如何导致通常有益或中性的微生物对特定组织（在这种情况下是心脏瓣膜）造成损害，说明了一种方法，通过这种方法，细菌可以成为机会性或意外的病原体。研究结果进一步表明，口腔微生物群中的某些聚糖结合链球菌可能易于产生感染性心内膜炎。
Streptococcus gordonii and Streptococcus sanguinis are primary colonizers of the tooth surface. Although generally non-pathogenic in the oral environment, they are a frequent cause of infective endocarditis. Both streptococcal species express a serine-rich repeat surface adhesin that mediates attachment to sialylated glycans on mucin-like glycoproteins, but the specific sialoglycan structures recognized can vary from strain to strain. Previous studies have shown that sialoglycan binding is clearly important for aortic valve infections caused by some S. gordonii, but this process did not contribute to the virulence of a strain of S. sanguinis. However, these streptococci can bind to different subsets of sialoglycan structures. Here we generated isogenic strains of S. gordonii that differ only in the type and range of sialoglycan structures to which they adhere and examined whether this rendered them more or less virulent in a rat model of endocarditis. The findings indicate that the recognition of specific sialoglycans can either enhance or diminish pathogenicity. Binding to sialyllactosamine reduces the initial colonization of mechanically-damaged aortic valves, whereas binding to the closely-related trisaccharide sialyl T-antigen promotes higher bacterial densities in valve tissue 72 hours later. A surprising finding was that the initial attachment of streptococci to aortic valves was inversely proportional to the affinity of each strain for platelets, suggesting that binding to platelets circulating in the blood may divert bacteria away from the endocardial surface. Importantly, we found that human and rat platelet GPIb alpha (the major receptor for S. gordonii and S. sanguinis on platelets) display similar O-glycan structures, comprised mainly of a di-sialylated core 2 hexasaccharide, although the rat GPIb alpha has a more heterogenous composition of modified sialic acids. The combined results suggest that streptococcal interaction with a minor O-glycan on GPIb alpha may be more important than the over-all affinity for GPIb alpha for pathogenic effects.Author summary Infective endocarditis (IE) is a life-threatening infection of heart valves, and streptococci that normally reside in the mouth are a leading cause of this disease. Some oral streptococcal species express a protein on their surface that enables attachment to glycan (sugar) modifications on saliva proteins, an interaction that may be important for colonization of the tooth and other oral surfaces. These "Siglec-like adhesins" are hypervariable in the type and number of glycan structures they bind, ranging from just one to more than six of the structures displayed on the saliva proteins. If streptococci enter into the bloodstream, the Siglec-like adhesin can mediate attachment to similar glycans that decorate platelet or plasma proteins, which can impact the overall virulence of the organism. This study highlights how recognition of a specific type of glycan structure can cause a generally beneficial or neutral microbe to create damage to specific tissues-in this case the heart valves, illustrating one means by which commensal bacteria can become opportunistic or accidental pathogens. The findings further indicate that certain glycan-binding streptococci among the oral microbiota may be predisposed to produce infective endocarditis.