Visualizing Pyrazinamide Action by Live Single-Cell Imaging of Phagosome Acidification and Mycobacterium tuberculosis pH Homeostasis.
Mycobacterium tuberculosis
antibiotics
human macrophages
intracellular pharmacokinetics
microenvironments
tuberculosis
Journal
mBio
ISSN: 2150-7511
Titre abrégé: mBio
Pays: United States
ID NLM: 101519231
Informations de publication
Date de publication:
26 04 2022
26 04 2022
Historique:
pubmed:
25
3
2022
medline:
29
4
2022
entrez:
24
3
2022
Statut:
ppublish
Résumé
Mycobacterium tuberculosis segregates within multiple subcellular niches with different biochemical and biophysical properties that, upon treatment, may impact antibiotic distribution, accumulation, and efficacy. However, it remains unclear whether fluctuating intracellular microenvironments alter mycobacterial homeostasis and contribute to antibiotic enrichment and efficacy. Here, we describe a live dual-imaging approach to monitor host subcellular acidification and M. tuberculosis intrabacterial pH. By combining this approach with pharmacological and genetic perturbations, we show that M. tuberculosis can maintain its intracellular pH independently of the surrounding pH in human macrophages. Importantly, unlike bedaquiline (BDQ), isoniazid (INH), or rifampicin (RIF), the drug pyrazinamide (PZA) displays antibacterial efficacy by disrupting M. tuberculosis intrabacterial pH homeostasis
Identifiants
pubmed: 35323041
doi: 10.1128/mbio.00117-22
pmc: PMC9040869
doi:
Substances chimiques
Antitubercular Agents
0
Pyrazinamide
2KNI5N06TI
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0011722Subventions
Organisme : European Respiratory Society (ERS)
ID : 713406
Organisme : Wellcome Trust (WT)
ID : 10092
Organisme : Cancer Research UK (CRUK)
ID : 10092
Organisme : EC | H2020 | H2020 Priority Excellent Science | H2020 Marie Skłodowska-Curie Actions (MSCA)
ID : 892859
Organisme : EC | H2020 | H2020 Priority Excellent Science | H2020 European Research Council (ERC)
ID : 772022
Organisme : UKRI | Medical Research Council (MRC)
ID : 10092
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