Introduction

A clear understanding of the metabolome of Mycobacterium tuberculosis and its target host cell during infection is fundamental for the development of novel diagnostic tools, effective drugs and vaccines required to combat tuberculosis. The surface-located Mycobacterium tuberculosis curli pili (MTP) adhesin forms initial contact with the host cell and is therefore important for the establishment of infection.

Objective

The aim of this investigation was to determine the role of MTP in modulating pathogen and host metabolic pathways in A549 epithelial cells infected with MTP proficient and deficient strains of M. tuberculosis.

Methods

Uninfected A549 epithelial cells, and those infected with M. tuberculosis V9124 wild-type strain, Δmtp and the mtp-complemented strains, were subjected to metabolite extraction, two-dimensional gas chromatography time-of-flight mass spectrometry (GCxGC-TOFMS) and bioinformatic analyses. Univariate and multivariate statistical tests were used to identify metabolites that were significantly differentially produced in the WT-infected and ∆mtp-infected A549 epithelial cell models, comparatively.

Results

A total of 46 metabolites occurred in significantly lower relative concentrations in the Δmtp-infected cells, indicating a reduction in nucleic acid synthesis, amino acid metabolism, glutathione metabolism, oxidative stress, lipid metabolism and peptidoglycan, compared to those cells infected with the WT strain.

Conclusion

The absence of MTP was associated with significant changes to the host metabolome, suggesting that this adhesin is an important contributor to the pathogenicity of M. tuberculosis, and supports previous findings of its potential as a suitable drug, vaccine and diagnostic target.

中文翻译：

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结核分枝杆菌菌毛（MTP）与A549上皮细胞感染模型中的重要宿主代谢途径相关，并有助于结核分枝杆菌的致病性

介绍

清楚了解结核分枝杆菌及其靶宿主细胞在感染过程中的代谢组是开发新型诊断工具，抗击结核病所需的有效药物和疫苗的基础。位于表面的结核分枝杆菌结核分枝杆菌（MTP）粘附素与宿主细胞形成初始接触，因此对于建立感染很重要。

目的

本研究的目的是确定MTP在结核分枝杆菌MTP熟练和缺陷菌株感染的A549上皮细胞中调节病原体和宿主代谢途径的作用。

方法

对未感染的A549上皮细胞以及感染了结核分枝杆菌V9124野生型菌株Δmtp和补充mtp的菌株进行代谢物提取，二维气相色谱飞行时间质谱（GCxGC-TOFMS）和生物信息学分析。比较而言，单变量和多变量统计检验用于鉴定在WT感染和∆ mtp感染的A549上皮细胞模型中差异显着产生的代谢物。

结果

与WT感染的那些细胞相比，Δmtp感染的细胞中总共有46种代谢物以相对较低的相对浓度发生，这表明核酸合成，氨基酸代谢，谷胱甘肽代谢，氧化应激，脂质代谢和肽聚糖的减少。应变。

结论

MTP的缺乏与宿主代谢组的显着变化有关，表明该粘附素是结核分枝杆菌致病性的重要贡献者，并支持其作为合适药物，疫苗和诊断靶标的潜力的先前发现。