Novel Clues on the Specific Association of Streptococcus gallolyticus subsp gallolyticus With Colorectal Cancer

Novel Clues on the Specific Association of Streptococcus gallolyticus subsp gallolyticus With Colorectal Cancer
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DOI:
10.1093/infdis/jiq169
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发表时间:
2011-04-15
影响因子:
6.4
通讯作者:
Tjalsma, Harold
Tjalsma, Harold
中科院分区:
医学2区
文献类型:
--
作者:
Boleij, Annemarie;Muytjens, Carla M. J.;Tjalsma, Harold

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背景解没食子链球菌解没食子亚种(牛链球菌生物型I)心内膜炎的患病率一般较低,但通常与结直肠癌有关。因此,本研究旨在揭示区分这种机会致病菌与一组(密切相关的)肠道细菌的毒力特征。在体外用分化的Caco-2细胞上的粘附、侵袭和易位测定重建感染途径。此外,以比较的方式分析了感染和细菌生物膜形成后的细胞免疫应答。S.已证明解没食子酸亚种菌株具有相对低的亲和力,并且不能内化上皮细胞。然而,这些细菌能够独特地在细胞旁穿过分化的上皮而不诱导上皮白细胞介素8或1 β应答。重要的是,它们具有在富含胶原蛋白的表面形成生物膜的出色能力,这种生物膜在体内存在于受损的心脏瓣膜和上皮移位的(癌前)部位。结论。总而言之,这些数据表明S.解没食子酸杆菌亚种具有独特的毒力因子库,其促进通过(前)恶性结肠病变的感染,并且随后可以在以下方面为该细菌提供竞争优势:(1)逃避先天免疫系统和(2)在结肠直肠癌易感患者的富含胶原的部位形成抗性赘生物。
Background. The prevalence of Streptococcus gallolyticus subsp gallolyticus ( Streptococcus bovis biotype I) endocarditis is in general low but very often linked to colorectal cancer. Therefore, this study aimed to reveal the virulence characteristics that distinguish this opportunistic pathogen from a panel of (closely related) intestinal bacteria.Methods. The route of infection was reconstructed in vitro with adhesion, invasion, and translocation assays on differentiated Caco-2 cells. Furthermore, cellular immune responses upon infection and bacterial biofilm formation were analyzed in a comparative manner.Results. S. gallolyticus subsp gallolyticus strains were demonstrated to have a relative low adhesiveness and could not internalize epithelial cells. However, these bacteria were uniquely able to paracellularly cross a differentiated epithelium without inducing epithelial interleukin 8 or 1 beta responses. Importantly, they had an outstanding ability to form biofilms on collagen-rich surfaces, which in vivo are found at damaged heart valves and (pre)cancerous sites with a displaced epithelium.Conclusions. Together, these data show that S. gallolyticus subsp gallolyticus has a unique repertoire of virulence factors that facilitate infection through (pre)malignant colonic lesions and subsequently can provide this bacterium with a competitive advantage in (1) evading the innate immune system and (2) forming resistant vegetations at collagen-rich sites in susceptible patients with colorectal cancer.