…
comment: The repository administrator has not yet configured an RDF license.
primary topic: Bioenergetic Heterogeneity in Mycobacterium tuberculosis Residing in Different Subcellular Niches

Bioenergetic Heterogeneity in Mycobacterium tuberculosis Residing in Different Subcellular Niches
type: AcademicArticle
type: Article
abstract: ATP/ADP depicts the bioenergetic state of Mycobacterium tuberculosis (Mtb). However, the metabolic state of Mtb during infection remains poorly defined due to the absence of appropriate tools. Perceval HR (PHR) was recently developed to measure intracellular ATP/ADP levels, but it cannot be employed in mycobacterial cells due to mycobacterial autofluorescence. Here, we reengineered the ATP/ADP sensor Perceval HR into PHR-mCherry to analyze ATP/ADP in fast- and slow-growing mycobacteria. ATP/ADP reporter strains were generated through the expression of PHR-mCherry. Using the Mtb reporter strain, we analyzed the changes in ATP/ADP levels in response to antimycobacterial agents. As expected, bedaquiline induced a decrease in ATP/ADP. Interestingly, the transcriptional inhibitor rifampicin led to the depletion of ATP/ADP levels, while the cell wall synthesis inhibitor isoniazid did not affect the ATP/ADP levels in Mtb. The usage of this probe revealed that Mtb faces depletion of ATP/ADP levels upon phagocytosis. Furthermore, we observed that the activation of macrophages with interferon gamma and lipopolysaccharides leads to metabolic stress in intracellular Mtb. Examination of the bioenergetics of mycobacteria residing in subvacuolar compartments of macrophages revealed that the bacilli residing in phagolysosomes and autophagosomes have significantly less ATP/ADP than the bacilli residing in phagosomes. These observations indicate that phagosomes represent a niche for metabolically active Mtb, while autophagosomes and phagolysosomes harbor metabolically quiescent bacilli. Interestingly, even in activated macrophages, Mtb residing in phagosomes remains metabolically active. We further observed that macrophage activation affects the metabolic state of intracellular Mtb through the trafficking of Mtb from phagosomes to autophagosomes and phagolysosomes. IMPORTANCE ATP/ADP levels guide bacterial cells, whether to replicate or to enter nonreplicating persistence. However, t…
date: 2021-06-29
volume: 12
issue: 3
status: peerReviewed
status: published
author list: authors
type: EPrint
type: ArticleEPrint
is part of: repository
subject: QR Microbiology

ASM JOURNALS
type: Organization

MBIO
type: Collection

Ashwani Kumar
type: Person
given name: Ashwani
family name: Kumar

Ajit Kumar Akela
type: Person
given name: Ajit Kumar
family name: Akela

HTML Summary of #2748 Bioenergetic Heterogeneity in Mycobacterium tuberculosis Residing in Different Subcellular Niches
format: text/html
primary topic: Bioenergetic Heterogeneity in Mycobacterium tuberculosis Residing in Different Subcellular Niches

QR Microbiology
type: Concept