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M. tuberculosis curli pili (MTP) is associated with alterations in carbon, fatty acid and amino acid metabolism in a THP-1 macrophage infection model. | LitMetric

M. tuberculosis curli pili (MTP) is associated with alterations in carbon, fatty acid and amino acid metabolism in a THP-1 macrophage infection model.

Microb Pathog

Medical Microbiology, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, 1st Floor Doris Duke Medical Research Institute, Congella, Private Bag 7, Durban, 4013, South Africa. Electronic address:

Published: May 2021

AI Article Synopsis

  • The study focuses on the initial interaction between the pathogen Mycobacterium tuberculosis (M. tuberculosis) and host macrophages, emphasizing the importance of understanding this process for developing treatments against tuberculosis.
  • The research specifically investigates M. tuberculosis curli pili (MTP), a surface adhesin that influences the metabolic pathways of both the pathogen and THP-1 macrophages during infection.
  • Findings revealed that the absence of MTP resulted in changes in key metabolites linked to carbon, fatty acid, and amino acid metabolism, indicating MTP's significant role in M. tuberculosis virulence and its potential as a diagnostic and therapeutic target.

Article Abstract

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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Source
http://dx.doi.org/10.1016/j.micpath.2021.104806DOI Listing

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