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.
Metabolomics
; 16(11): 116, 2020 10 21.
Article
en En
| MEDLINE
| ID: mdl-33084984
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tuberculosis
/
Fimbrias Bacterianas
/
Células Epiteliales
/
Redes y Vías Metabólicas
/
Mycobacterium tuberculosis
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Metabolomics
Año:
2020
Tipo del documento:
Article
País de afiliación:
Sudáfrica