结核分枝杆菌
微生物学
巨噬细胞
细菌粘附素
肺结核
病菌
代谢组
生物
脂肪酸
毒力
新陈代谢
化学
生物化学
代谢物
体外
医学
基因
病理
作者
Shinese Ashokcoomar,Du Toit Loots,Derylize Beukes,Mari van Reenen,Balakrishna Pillay,Manormoney Pillay
标识
DOI:10.1016/j.micpath.2021.104806
摘要
The initial host-pathogen interaction is crucial for the establishment of infection. An improved understanding of the pathophysiology of Mycobacterium tuberculosis (M. tuberculosis) during macrophage infection can aid the development of intervention therapeutics against tuberculosis. M. tuberculosis curli pili (MTP) is a surface located adhesin, involved in the first point-of-contact between pathogen and host. This study aimed to better understand the role of MTP in modulating the intertwined metabolic pathways of M. tuberculosis and its THP-1 macrophage host. Metabolites were extracted from pelleted wet cell mass of THP-1 macrophages infected with M. tuberculosis wild-type V9124 (WT), Δmtp-deletion mutant and the mtp-complemented strains, respectively, via a whole metabolome extraction method using a 1:3:1 ratio of chloroform:methanol:water. Metabolites were detected by two-dimensional gas chromatography time-of-flight mass spectrometry. Significant metabolites were determined through univariate and multivariate statistical tests and online pathway databases. Relative to the WT, a total of nine and ten metabolites were significantly different in the Δmtp and complement strains, respectively. All nine significant metabolites were found in elevated levels in the Δmtp relative to the WT. Additionally, of the ten significant metabolites, eight were detected in lower levels and two were detected in higher levels in the complement relative to the WT. The absence of the MTP adhesin resulted in reduced virulence of M. tuberculosis leading to alterations in metabolites involved in carbon, fatty acid and amino acid metabolism during macrophage infection, suggesting that MTP plays an important role in the modulation of host metabolic activity. These findings support the prominent role of the MTP adhesin as a virulence factor as well as a promising biomarker for possible diagnostic and therapeutic intervention.
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