Plasmid-Encoded Pgp3 Is a Major Virulence Factor for Chlamydia muridarum To Induce Hydrosalpinx in Mice
Plasmid-Encoded Pgp3 Is a Major Virulence Factor for Chlamydia muridarum To Induce Hydrosalpinx in Mice
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DOI：
10.1128/iai.02576-14
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发表时间：
2014-12-01
影响因子：
3.1
通讯作者：
Zhong, Guangming
中科院分区：
文献类型：
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作者：
Liu, Yuanjun;Huang, Yumeng;Zhong, Guangming
用小鼠衣原体感染诱导小鼠输卵管积水，这是一种用于研究衣原体感染的模型。已知女性沙眼的发病机制依赖于编码八个基因的隐蔽质粒，这些基因被命名为pgp 1至pgp 8。为了确定质粒编码的致病决定因素，我们评估了C。用于诱导输卵管积水的质粒携带基因pgp 3、pgp-4或pgp-7缺陷的鼠耳球虫转化体。C.具有pgp 3或pgp-4但不具有pgp-7的框内缺失的鼠伤寒沙门氏菌转化体不能诱导输卵管积水。通过使用在相应的pgp基因中具有提前终止密码子插入的转化体（以使缺失突变体中固有的极性效应最小化）来再现缺失突变体表型。已知Pgp 4调节Pgp 3的表达，而Pgp 3的缺乏并不显著影响Pgp 4的功能。因此，我们得出结论，Pgp 3是一个效应毒力因子，Pgp 3的缺失可能是导致C.上述的鼠伤寒致病性。这种减弱的致病性进一步与感染衣原体的小鼠下生殖道衣原体存活率的快速下降和上生殖道衣原体Ascension的减少相关。Pgp 3缺失而Pgp 7不缺失。Pgp 3缺陷型C.当在接种后第7天直接递送到输卵管时，鼠尾菌生物体的侵入性也较小。这些观察结果表明，质粒编码的Pgp 3是C.鼠伤寒沙门氏菌在小鼠生殖道中存活，并且代表了C.鼠伤寒致病机理的研究。
Hydrosalpinx induction in mice by Chlamydia muridarum infection, a model that has been used to study C. trachomatis pathogenesis in women, is known to depend on the cryptic plasmid that encodes eight genes designated pgp1 to pgp8. To identify the plasmid-encoded pathogenic determinants, we evaluated C. muridarum transformants deficient in the plasmid-borne gene pgp3, -4, or -7 for induction of hydrosalpinx. C. muridarum transformants with an in-frame deletion of either pgp3 or -4 but not -7 failed to induce hydrosalpinx. The deletion mutant phenotype was reproduced by using transformants with premature termination codon insertions in the corresponding pgp genes (to minimize polar effects inherent in the deletion mutants). Pgp4 is known to regulate pgp3 expression, while lack of Pgp3 does not significantly affect Pgp4 function. Thus, we conclude that Pgp3 is an effector virulence factor and that lack of Pgp3 may be responsible for the attenuation in C. muridarum pathogenicity described above. This attenuated pathogenicity was further correlated with a rapid decrease in chlamydial survival in the lower genital tract and reduced ascension to the upper genital tract in mice infected with C. muridarum deficient in Pgp3 but not Pgp7. The Pgp3-deficient C. muridarum organisms were also less invasive when delivered directly to the oviduct on day 7 after inoculation. These observations demonstrate that plasmid-encoded Pgp3 is required for C. muridarum survival in the mouse genital tract and represents a major virulence factor in C. muridarum pathogenesis in mice.