Mycobacterium tuberculosis curli pili (MTP) deficiency is associated with alterations in cell wall biogenesis, fatty aci
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ORIGINAL ARTICLE
Mycobacterium tuberculosis curli pili (MTP) deficiency is associated with alterations in cell wall biogenesis, fatty acid metabolism and amino acid synthesis S. Ashokcoomar1 · K. S. Reedoy1 · S. Senzani1 · D. T. Loots3 · D. Beukes3 · M. van Reenen3 · B. Pillay2 · M. Pillay1 Received: 24 April 2020 / Accepted: 28 August 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract 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. Keywords M. tuberculosis curli pili · mtp · Adhesin · GC × GC-TOFMS · Metabolomics
1 Introduction S. Ashokcoomar and K. S. Reedoy Joint first authors Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11306-020-01720-z) contains supplementary material, which is available to authorized users.
Tuberculosis (TB), caused by Mycobacterium tuberculosis, still poses a global threat, not only to health, but also to socio-economics, particularly in low and middle income countries (WHO 2019). An estimated 10 million incident
* M. Pillay [email protected] 1
Discipline of Medical Microbiology, School of Laboratory Medicine and Medical Sciences, College
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