A pathogenicity locus of Streptococcus gallolyticus subspecies gallolyticus.

A pathogenicity locus of Streptococcus gallolyticus subspecies gallolyticus.
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DOI:
10.1038/s41598-023-33178-z
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发表时间:
2023-04-18
期刊:
影响因子:
4.6
通讯作者:
Xu, Yi
Xu, Yi
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Taylor, John Culver;Kumar, Ritesh;Xu, Juan;Xu, Yi

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已知解没食子酸链球菌亚种(Sgg)与结直肠癌(CRC)密切相关。最近的功能研究进一步表明,Sgg积极刺激CRC细胞增殖,促进结肠肿瘤的发展。然而,对于Sgg的促增殖和促肿瘤活性重要的Sgg因子仍不清楚。在这里,我们确定了一个染色体位点在SGG株TX 20005。该基因座的缺失显著降低了Sgg对CRC细胞的粘附,并消除了Sgg刺激CRC细胞增殖的能力。因此,我们将该位点命名为Sgg致病相关区(SPAR)。更重要的是,我们发现SPAR对Sgg的体内致病性很重要。在肠道定殖模型中,暴露于SPAR缺失突变体的小鼠显示结肠组织和粪便材料中的Sgg负荷显著降低,表明SPAR有助于Sgg的定殖能力。在CRC的小鼠模型中,SPAR的缺失消除了Sgg促进结肠肿瘤生长发展的能力。总之,这些结果突出了SPAR作为Sgg的关键致病性决定因素。
Streptococcus gallolyticus subspecies gallolyticus (Sgg) is known to be strongly associated with colorectal cancer (CRC). Recent functional studies further demonstrated that Sgg actively stimulates CRC cell proliferation and promotes the development of colon tumors. However, the Sgg factors important for the pro-proliferative and pro-tumor activities of Sgg remain unclear. Here, we identified a chromosomal locus in Sgg strain TX20005. Deletion of this locus significantly reduced Sgg adherence to CRC cells and abrogated the ability of Sgg to stimulate CRC cell proliferation. Thus, we designate this locus as the Sgg pathogenicity-associated region (SPAR). More importantly, we found that SPAR is important for Sgg pathogenicity in vivo. In a gut colonization model, mice exposed to the SPAR deletion mutant showed significantly reduced Sgg load in the colonic tissues and fecal materials, suggesting that SPAR contributes to the colonization capacity of Sgg. In a mouse model of CRC, deletion of SPAR abolished the ability of Sgg to promote the development of colon tumors growth. Taken together, these results highlight SPAR as a critical pathogenicity determinant of Sgg.
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