Untargeted metabolomics analysis reveals Mycobacterium tuberculosis strain H37Rv specifically induces tryptophan metabolism in human macrophages

被引：9

作者：

Xiao, Guohui ^{[1
]}

Zhang, Su ^{[1
]}

Zhang, Like ^{[2
]}

Liu, Shuyan ^{[1
]}

Li, Guobao ^{[1
]}

Ou, Min ^{[1
]}

Zeng, Xuan ^{[1
]}

Wang, Zhaoqin ^{[1
]}

Zhang, Guoliang ^{[1
,2
]}

Lu, Shuihua ^{[1
]}

机构：

[1] Southern Univ Sci & Technol, Shenzhen Peoples Hosp 3, Guangdong Prov Clin Res Ctr TB, Natl Clin Res Ctr Infect Dis, Shenzhen 518112, Peoples R China

[2] Guangdong Med Univ, Sch Basic Med Sci, Dongguan, Peoples R China

来源：

BMC MICROBIOLOGY | 2022年 / 22卷 / 01期

基金：

中国国家自然科学基金;

关键词：

mycobacterium tuberculosis; Metabolome; THP-1; Tryptophan metabolism; Virulence; INDOLEAMINE 2,3-DIOXYGENASE ACTIVITY; INTRACELLULAR GROWTH; CELL-DEATH; APOPTOSIS; THP-1; PATHWAY; MONOCYTES; VIRULENCE; DEPLETION; NECROSIS;

D O I：

10.1186/s12866-022-02659-y

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Background Tuberculosis (TB) caused by Mycobacterium tuberculosis (M. tb) remains a global health issue. The characterized virulent M. tb H37Rv, avirulent M. tb H37Ra and BCG strains are widely used as reference strains to investigate the mechanism of TB pathogenicity. Here, we attempted to determine metabolomic signatures associated with the Mycobacterial virulence in human macrophages through comparison of metabolite profile in THP-1-derived macrophages following exposure to the M. tb H37Rv, M. tb H37Ra and BCG strains. Results Our findings revealed remarkably changed metabolites in infected macrophages compared to uninfected macrophages. H37Rv infection specifically induced 247 differentially changed metabolites compared to H37Ra or BCG infection. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed H37Rv specifically induces tryptophan metabolism. Moreover, quantitative PCR (qPCR) results showed that indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase 2 (TDO2) which converts the tryptophan to a series of biologically second metabolites were up-regulated in H37Rv-infected macrophages compared to H37Ra- or BCG-infected macrophages, confirming the result of enhanced tryptophan metabolism induced by H37Rv infection. These findings indicated that targeting tryptophan (Trp) metabolism may be a potential therapeutic strategy for pulmonary TB. Conclusions We identified a number of differentially changed metabolites that specifically induced in H37Rv infected macrophages. These signatures may be associated with the Mycobacterial virulence in human macrophages. The present findings provide a better understanding of the host response associated with the virulence of the Mtb strain.

引用

页数：10

共 47 条

[21] Depletion of alveolar macrophages exerts protective effects in pulmonary tuberculosis in mice [J].