Introduction

In an effort to find alternative therapeutic interventions to combat tuberculosis, a better understanding of the pathophysiology of Mycobacterium tuberculosis is required. The Mycobacterium tuberculosis curli pili (MTP) adhesin, present on the surface of this pathogen, has previously been shown using functional genomics and global transcriptomics, to play an important role in establishing infection, bacterial aggregation, and modulating host response in vitro and in vivo.

Objective

This investigation aimed to determine the role of MTP in modulating the metabolism of M. tuberculosis, using mtp gene-knockout mutant and complemented strains.

Methods

Untargeted two-dimensional gas chromatography time-of-flight mass spectrometry, and bioinformatic analyses, were used to identify significant differences in the metabolite profiles among the wild-type, ∆mtp mutant and mtp-complemented strains, and validated with results generated by real-time quantitative PCR.

Results

A total of 28 metabolites were found to be significantly altered when comparing the ∆mtp mutant and the wild-type strains indicating a decreased utilisation of metabolites in cell wall biogenesis, a reduced efficiency in the breakdown of fatty acids, and decreased amino acid biosynthesis in the former strain. Comparison of the wild-type to mtp-complement, and ∆mtp to mtp-complemented strains revealed 10 and 16 metabolite differences, respectively. Real-time quantitative PCR results supported the metabolomics findings. Complementation of the ∆mtp mutant resulted in a partial restoration of MTP function.

Conclusion

The lack of the MTP adhesin resulted in various bacterial cell wall alterations and related metabolic changes. This study highlights the importance of MTP as a virulence factor and further substantiates its potential use as a suitable biomarker for the development of diagnostic tools and intervention therapeutics against TB.

中文翻译：

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结核分枝杆菌（MTP）缺陷与细胞壁生物发生，脂肪酸代谢和氨基酸合成的改变有关。

介绍

为了找到其他抗结核治疗方法，需要对结核分枝杆菌的病理生理有更好的了解。该病原体表面上存在的结核分枝杆菌黏附素（MTP）粘附素先前已通过功能基因组学和整体转录组学证明在建立感染，细菌聚集和调节宿主体内和体外反应中起重要作用。

目的

此调查的目的是确定在调节代谢MTP的作用结核分枝杆菌，使用MTP基因敲除突变体和补充菌株。

方法

使用非目标二维气相色谱飞行时间质谱和生物信息学分析来鉴定野生型，Δmtp突变体和mtp互补菌株之间的代谢物谱差异显着，并用真实产生的结果进行验证实时定量PCR。

结果

比较Δmtp突变体和野生型菌株时，发现总共28种代谢物发生了显着变化，表明代谢物在细胞壁生物发生中的利用减少，脂肪酸分解的效率降低以及在土壤中的氨基酸生物合成减少。前者。将野生型与mtp互补菌株以及∆ mtp与mtp互补菌株进行比较，分别发现了10和16种代谢物差异。实时定量PCR结果支持代谢组学研究结果。Δmtp突变体的互补导致MTP功能的部分恢复。

结论

MTP粘附素的缺乏导致各种细菌细胞壁改变和相关的代谢变化。这项研究强调了MTP作为毒力因子的重要性，并进一步证实了MTP作为开发针对结核病的诊断工具和干预疗法的合适生物标志物的潜在用途。