Department of Medicine, Indiana University, Indianapolis, Indiana, USA.
Targeted Metabolomics and Proteomics Laboratory, University of Alabama at Birmingham, Birmingham, Alabama, USA.
J Infect Dis. 2023 Oct 18;228(8):1119-1126. doi: 10.1093/infdis/jiad155.
Natural clearance of Chlamydia trachomatis in women occurs in the interval between screening and treatment. In vitro, interferon-γ (IFN-γ)-mediated tryptophan depletion results in C. trachomatis clearance, but whether this mechanism occurs in vivo remains unclear. We previously found that women who naturally cleared C. trachomatis had lower cervicovaginal levels of tryptophan and IFN-γ compared to women with persisting infection, suggesting IFN-γ-independent pathways may promote C. trachomatis clearance.
Cervicovaginal lavages from 34 women who did (n = 17) or did not (n = 17) naturally clear C. trachomatis were subjected to untargeted high-performance liquid chromatography mass-spectrometry to identify metabolites and metabolic pathways associated with natural clearance.
In total, 375 positively charged metabolites and 149 negatively charged metabolites were annotated. Compared to women with persisting infection, C. trachomatis natural clearance was associated with increased levels of oligosaccharides trehalose, sucrose, melezitose, and maltotriose, and lower levels of indoline and various amino acids. Metabolites were associated with valine, leucine, and isoleucine biosynthesis pathways.
The cervicovaginal metabolome in women who did or did not naturally clear C. trachomatis is distinct. In women who cleared C. trachomatis, depletion of various amino acids, especially valine, leucine, and isoleucine, suggests that amino acids other than tryptophan impact C. trachomatis survival in vivo.
沙眼衣原体在女性中的自然清除发生在筛查和治疗之间的间隔内。在体外,干扰素-γ(IFN-γ)介导的色氨酸耗竭导致沙眼衣原体清除,但这种机制是否在体内发生尚不清楚。我们之前发现,与持续感染的女性相比,自然清除沙眼衣原体的女性的宫颈阴道色氨酸和 IFN-γ水平较低,这表明 IFN-γ 不依赖的途径可能促进沙眼衣原体的清除。
对 34 名自然清除沙眼衣原体的女性(n=17)和未清除沙眼衣原体的女性(n=17)的宫颈阴道灌洗液进行非靶向高效液相色谱-质谱分析,以鉴定与自然清除相关的代谢物和代谢途径。
总共鉴定出 375 种带正电荷的代谢物和 149 种带负电荷的代谢物。与持续感染的女性相比,沙眼衣原体自然清除与寡糖海藻糖、蔗糖、梅利托糖和麦芽三糖水平升高,以及吲哚啉和各种氨基酸水平降低相关。代谢物与缬氨酸、亮氨酸和异亮氨酸生物合成途径相关。
自然清除或未清除沙眼衣原体的女性的宫颈阴道代谢组学是不同的。在清除沙眼衣原体的女性中,各种氨基酸,特别是缬氨酸、亮氨酸和异亮氨酸的耗竭表明,除色氨酸外,其他氨基酸会影响沙眼衣原体在体内的存活。