Mycobacterium tuberculosis curli pili (MTP) is associated with significant host metabolic pathways in an A549 epithelial
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ORIGINAL ARTICLE
Mycobacterium tuberculosis curli pili (MTP) is associated with significant host metabolic pathways in an A549 epithelial cell infection model and contributes to the pathogenicity of Mycobacterium tuberculosis K. S. Reedoy1 · D. T. Loots3 · D. Beukes3 · M. van Reenen3 · B. Pillay2 · M. Pillay1 Received: 26 May 2020 / Accepted: 2 October 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract 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. Keywords M. tuberculosis curli pili · A549 epithelial cells · mtp · Adhesin · GCxGC-TOFMS · Metabolomics
1 Introduction
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11306-020-01736-5) contains supplementary material, which is available to authorized users. * M. Pillay [email protected] 1
Medical Microbiology School of Laboratory Medicine and Medical Sciences, College of Health Sciences, Doris Duke Medical Research Institute, University of KwaZuluNatal, 1st Floor, Congella, Private Bag 7, Durban 4013, South Africa
Mycobacterium tuberculosis, one of the top ten death-causing organisms by a single infectious entity, is the etiological agent of the worldwide epidemic, tuberculosis (TB) (Centers for Disease Control and Prevention (CDC) 2018). In 2018 2
School of Life Sciences, College of
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