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Lactate Acquisition Promotes Successful Colonization of the Murine Genital Tract by Neisseria gonorrhoeae

机译:乳酸的吸收促进淋病奈瑟氏菌成功定殖小鼠生殖道

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Previous studies on Neisseria gonorrhoeae have demonstrated that metabolism of lactate in the presence of glucose increases the growth rate of the bacterium and enhances its resistance to complement-mediated killing. Although these findings in vitro suggest that the acquisition of lactate promotes gonococcal colonization, the significance of this carbon source to the survival of the gonococcus in vivo remains unknown. To investigate the importance of lactate utilization during Neisseria gonorrhoeae genital tract infection, we identified the gene lctP, which encodes the gonococcal lactate permease. A mutant that lacks a functional copy of lctP was unable to take up exogenous lactate and did not grow in defined medium with lactate as the sole carbon source, in contrast to the wild-type and complemented strains; the mutant strain exhibited no growth defect in defined medium containing glucose. In defined medium containing physiological concentrations of lactate and glucose, the lctP mutant demonstrated reduced early growth and increased sensitivity to complement-mediated killing compared with the wild-type strain; the enhanced susceptibility to complement was associated with a reduction in lipopolysaccharide sialylation of the lctP mutant. The importance of lactate utilization during colonization was evaluated in the murine model of lower genital tract infection. The lctP mutant was significantly attenuated in its ability to colonize and survive in the genital tract, while the complemented mutant exhibited no defect for colonization. Lactate is a micronutrient in the genital tract that contributes to the survival of the gonococcus.
机译:先前对淋病奈瑟氏菌的研究表明,在葡萄糖存在下乳酸的代谢会增加细菌的生长速率,并增强其对补体介导的杀伤的抵抗力。尽管这些体外发现表明乳酸的获取促进了淋球菌的定殖,但是这种碳源对淋球菌在体内存活的重要性仍然未知。为了调查淋病奈瑟氏球菌生殖道感染中乳酸利用的重要性,我们鉴定了编码淋球菌乳酸通透酶的基因 lctP 。与野生型和互补型菌株相比,缺少 lctP 功能性拷贝的突变体无法吸收外源乳酸,并且不能在以乳酸为唯一碳源的特定培养基中生长。突变菌株在含葡萄糖的特定培养基中没有生长缺陷。与野生型菌株相比,在包含生理浓度的乳酸和葡萄糖的特定培养基中, lctP 突变体显示出早期生长降低和对补体介导的杀伤的敏感性增加。补体的敏感性增强与 lctP 突变体的脂多糖唾液酸化作用降低有关。在下生殖道感染的小鼠模型中评估了定殖过程中乳酸利用的重要性。 lctP 突变体在生殖道中定殖和存活的能力显着减弱,而互补的突变体没有定植缺陷。乳酸是生殖道中的微量营养素,有助于淋球菌的存活。

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