Evaluation of a Yersinia pestis mutant impaired in a thermoregulated type VI-like secretion system in flea, macrophage and murine models.

Evaluation of a Yersinia pestis mutant impaired in a thermoregulated type VI-like secretion system in flea, macrophage and murine models.
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DOI:
10.1016/j.micpath.2009.08.005
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发表时间:
2009-11
影响因子:
3.8
通讯作者:
Motin VL
Motin VL
中科院分区:
医学3区
文献类型:
--
作者:
Robinson JB;Telepnev MV;Zudina IV;Bouyer D;Montenieri JA;Bearden SW;Gage KL;Agar SL;Foltz SM;Chauhan S;Chopra AK;Motin VL

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最近在几种革兰氏阴性生物体中发现了 VI 型分泌系统 (T6SS),并已证明其与某些细菌病原体的毒力有关。删除鼠疫耶尔森菌 CO92(基因座 YPO0499-YPO0516)的 T6SS,然后研究该突变的表型。我们观察到,与 37°C 相比,鼠疫耶尔森氏菌的 T6SS 基因座在 26°C 下优先表达,表明其可能在跳蚤循环中发挥作用。然而,我们发现鼠疫耶尔森氏菌CO92中T6SS位点YPO0499-YPO0516的缺失对该菌株感染东方鼠蚤(印客客蚤)的能力没有影响。然而,在 26°C 下预生长的细菌细胞感染 20 小时后,该突变体在巨噬细胞样 J774.A1 细胞中显示出细胞内数量增加,表明该 T6SS 基因座的表达限制了巨噬细胞中的细胞内复制。此外,YPO0499-YPO0516位点的缺失减少了巨噬细胞对37°C下预生长的鼠疫耶尔森氏菌突变体的摄取,表明该T6SS位点具有吞噬促进活性。对鼠腺鼠疫和吸入性鼠疫模型中 T6SS 突变体毒力的进一步研究表明,与亲本 CO92 菌株相比,没有减弱。
Type VI secretion systems (T6SS) have been identified recently in several Gram-negative organisms and have been shown to be associated with virulence in some bacterial pathogens. A T6SS of Yersinia pestis CO92 (locus YPO0499-YPO0516) was deleted followed by investigation of the phenotype of this mutation. We observed that this T6SS locus of Y. pestis was preferentially expressed at 26° C in comparison to 37° C suggesting a possible role in the flea cycle. However, we found that the deletion of T6SS locus YPO0499-YPO0516 in Y. pestis CO92 had no effect on the ability of this strain to infect the oriental rat flea, Xenopsylla cheopis. Nevertheless, this mutant displayed increased intracellular numbers in macrophage-like J774.A1 cells after 20 hours postinfection for bacterial cells pre-grown at 26° C indicating that expression of this T6SS locus limited intracellular replication in macrophages. In addition, deletion of the YPO0499-YPO0516 locus reduced the uptake by macrophages of the Y. pestis mutant pre-grown at 37°C, suggesting that this T6SS locus has phagocytosis-promoting activity. Further study of the virulence of the T6SS mutant in murine bubonic and inhalation plague models revealed no attenuation in comparison with the parental CO92 strain.
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