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Infectivity Acts as In Vivo Selection for Maintenance of the Chlamydial Cryptic Plasmid

机译：感染性作为体内选择以维持衣原体隐性质粒

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Chlamydia trachomatis contains a conserved ～7.5-kb plasmid. Loss of the plasmid results in reduced glycogen accumulation, failure to activate TLR2, and reduced infectivity. We hypothesized that reduced infectivity functions as a means of selection for plasmid maintenance. We directly examined the biological significance of the reduced infectivity associated with plasmid deficiency by determining the relative fitness of plasmid-deficient CM972 versus that of wild-type C. muridarum Nigg in mixed inocula in vitro and in vivo. C. muridarum Nigg rapidly out-competed its plasmid-cured derivative CM972 in vitro but was not competitive with CM3.1, a derivative of CM972 that has reverted to a normal infectivity phenotype. C. muridarum Nigg also effectively competed with CM972 during lower and upper genital tract infection in the mouse, demonstrating that strong selective pressure for plasmid maintenance occurs during infection. The severity of oviduct inflammation and dilatation resulting from these mixed infections correlated directly with the amount of C. muridarum Nigg in the initial inoculum, confirming the role of the plasmid in virulence. Genetic characterization of CM972 and CM3.1 revealed no additional mutations (other than loss of the plasmid) to account for the reduced infectivity of CM972 and detected a single base substitution in TC_0236 in CM3.1 that may be responsible for its restored infectivity. These data demonstrate that a chlamydial strain that differs genetically from its wild-type parent only with respect to the lack of the chlamydial plasmid is unable to compete in vitro and in vivo, likely explaining the rarity of plasmid-deficient isolates in nature.
机译：沙眼衣原体含有一个〜7.5-kb的保守质粒。质粒的丢失导致糖原积累减少，激活TLR2失败和感染性降低。我们假设降低的传染性充当质粒维持选择的一种手段。我们通过确定质粒缺陷的CM972与野生型 C的相对适应性，直接检查了与质粒缺乏相关的传染性降低的生物学意义。体内和体外的混合接种物中的黑murmurum Nigg。 C。 Nigg在体外迅速胜过其质粒固化的衍生物CM972 ，但与CM3.1的竞争性不强，后者已恢复为正常的传染性表型。 C。在小鼠下生殖道和上生殖道感染期间，Nigg还可以有效地与CM972竞争，这表明在感染过程中会发生很强的选择质粒维持压力。这些混合感染导致的输卵管炎症和扩张的严重程度与 C量直接相关。最初的接种物中含有muridarum Nigg，证实了质粒在毒力中的作用。 CM972和CM3.1的遗传特征表明，没有其他突变（除了质粒丢失）来解释CM972的感染性降低，并且在CM3.1的TC_0236中检测到单个碱基取代，这可能是其恢复感染性的原因。这些数据表明，就衣原体质粒的缺乏而言，仅与衣原体亲本在遗传上不同的衣原体菌株无法与体外和体内竞争，可能解释了自然界中缺乏质粒的分离株的稀有性。

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