Symbiotic Relationship between Streptococcus mutans and Candida albicans Synergizes Virulence of Plaque Biofilms In Vivo
Symbiotic Relationship between Streptococcus mutans and Candida albicans Synergizes Virulence of Plaque Biofilms In Vivo
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DOI：
10.1128/iai.00087-14
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发表时间：
2014-05-01
影响因子：
3.1
通讯作者：
Koo, Hyun
中科院分区：
文献类型：
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作者：
Falsetta, Megan L.;Klein, Marlise I.;Koo, Hyun
变形链球菌是龋病，特别是儿童早期龋病的主要致病菌。S.变形链球菌可能不是单独作用的;白色念珠菌细胞经常与变形链球菌的严重感染沿着被检测到。受ECC影响的儿童的菌斑生物膜中的变形菌。这种关联是否参与了生物膜毒力的增强，仍有待阐明。我们发现，这些生物体在体外和体内共同形成生物膜的能力得到增强。C.白念珠菌增加胞外多糖（EPS）的产生，使得同种生物膜积累更多的生物量，并容纳更多的活S。变形细胞比单一物种生物膜。所得的三维生物膜结构显示出相当大的S。变形菌小菌落被真菌细胞包围，这些真菌细胞被密集的富含EPS的基质包围。使用啮齿动物模型，我们探讨了这种跨王国的相互作用的龋齿的发病机制的影响。与单独感染任一种的动物相比，合并感染的动物显示出更高水平的感染和菌斑生物膜内的微生物携带。此外，合并感染协同增强生物膜毒力，导致疾病的侵袭性发作，并伴有猖獗的龋损。我们的体外实验数据还表明，葡萄糖基转移酶衍生的EPS是同种生物膜形成的关键介质，并且与C.白念珠菌诱导S.变异体（例如，gtfB，fabM）。我们还发现，葡聚糖衍生的β 1，3-葡聚糖有助于EPS基质结构，而真菌甘露聚糖和β-葡聚糖提供GtfB结合和活性的位点。总之，我们证明了一种新的互利共生的细菌-真菌的关系，发生在临床相关的网站，以放大普遍存在的传染病的严重性。
Streptococcus mutans is often cited as the main bacterial pathogen in dental caries, particularly in early-childhood caries (ECC). S. mutans may not act alone; Candida albicans cells are frequently detected along with heavy infection by S. mutans in plaque biofilms from ECC-affected children. It remains to be elucidated whether this association is involved in the enhancement of biofilm virulence. We showed that the ability of these organisms together to form biofilms is enhanced in vitro and in vivo. The presence of C. albicans augments the production of exopolysaccharides (EPS), such that cospecies biofilms accrue more biomass and harbor more viable S. mutans cells than single-species biofilms. The resulting 3-dimensional biofilm architecture displays sizeable S. mutans microcolonies surrounded by fungal cells, which are enmeshed in a dense EPS-rich matrix. Using a rodent model, we explored the implications of this cross-kingdom interaction for the pathogenesis of dental caries. Coinfected animals displayed higher levels of infection and microbial carriage within plaque biofilms than animals infected with either species alone. Furthermore, coinfection synergistically enhanced biofilm virulence, leading to aggressive onset of the disease with rampant carious lesions. Our in vitro data also revealed that glucosyltransferase-derived EPS is a key mediator of cospecies biofilm development and that coexistence with C. albicans induces the expression of virulence genes in S. mutans (e.g., gtfB, fabM). We also found that Candida-derived beta 1,3-glucans contribute to the EPS matrix structure, while fungal mannan and beta-glucan provide sites for GtfB binding and activity. Altogether, we demonstrate a novel mutualistic bacterium-fungus relationship that occurs at a clinically relevant site to amplify the severity of a ubiquitous infectious disease.