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Preexisting Heterogeneity of Inducible Nitric Oxide Synthase Expression Drives Differential Growth of Mycobacterium tuberculosis in Macrophages

Mycobacterium tuberculosis infection is initiated by the inhalation and implantation of bacteria in the lung alveoli, where they are phagocytosed by macrophages. Even a single bacterium may be sufficient to initiate infection. Thereafter, the clinical outcome is highly variable between individuals,...

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Detalles Bibliográficos
Autores principales: Rutschmann, Ophélie, Toniolo, Chiara, McKinney, John D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9600446/
https://www.ncbi.nlm.nih.gov/pubmed/36121153
http://dx.doi.org/10.1128/mbio.02251-22
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author Rutschmann, Ophélie
Toniolo, Chiara
McKinney, John D.
author_facet Rutschmann, Ophélie
Toniolo, Chiara
McKinney, John D.
author_sort Rutschmann, Ophélie
collection PubMed
description Mycobacterium tuberculosis infection is initiated by the inhalation and implantation of bacteria in the lung alveoli, where they are phagocytosed by macrophages. Even a single bacterium may be sufficient to initiate infection. Thereafter, the clinical outcome is highly variable between individuals, ranging from sterilization to active disease, for reasons that are not well understood. Here, we show that the rate of intracellular bacterial growth varies markedly between individual macrophages, and this heterogeneity is driven by cell-to-cell variation of inducible nitric oxide synthase (iNOS) activity. At the single-cell level, iNOS expression fluctuates over time, independent of infection or activation with gamma interferon. We conclude that chance encounters between individual bacteria and host cells randomly expressing different levels of an antibacterial gene can determine the outcome of single-cell infections, which may explain why some exposed individuals clear the bacteria while others develop progressive disease.
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spelling pubmed-96004462022-10-27 Preexisting Heterogeneity of Inducible Nitric Oxide Synthase Expression Drives Differential Growth of Mycobacterium tuberculosis in Macrophages Rutschmann, Ophélie Toniolo, Chiara McKinney, John D. mBio Research Article Mycobacterium tuberculosis infection is initiated by the inhalation and implantation of bacteria in the lung alveoli, where they are phagocytosed by macrophages. Even a single bacterium may be sufficient to initiate infection. Thereafter, the clinical outcome is highly variable between individuals, ranging from sterilization to active disease, for reasons that are not well understood. Here, we show that the rate of intracellular bacterial growth varies markedly between individual macrophages, and this heterogeneity is driven by cell-to-cell variation of inducible nitric oxide synthase (iNOS) activity. At the single-cell level, iNOS expression fluctuates over time, independent of infection or activation with gamma interferon. We conclude that chance encounters between individual bacteria and host cells randomly expressing different levels of an antibacterial gene can determine the outcome of single-cell infections, which may explain why some exposed individuals clear the bacteria while others develop progressive disease. American Society for Microbiology 2022-09-19 /pmc/articles/PMC9600446/ /pubmed/36121153 http://dx.doi.org/10.1128/mbio.02251-22 Text en Copyright © 2022 Rutschmann et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Rutschmann, Ophélie
Toniolo, Chiara
McKinney, John D.
Preexisting Heterogeneity of Inducible Nitric Oxide Synthase Expression Drives Differential Growth of Mycobacterium tuberculosis in Macrophages
title Preexisting Heterogeneity of Inducible Nitric Oxide Synthase Expression Drives Differential Growth of Mycobacterium tuberculosis in Macrophages
title_full Preexisting Heterogeneity of Inducible Nitric Oxide Synthase Expression Drives Differential Growth of Mycobacterium tuberculosis in Macrophages
title_fullStr Preexisting Heterogeneity of Inducible Nitric Oxide Synthase Expression Drives Differential Growth of Mycobacterium tuberculosis in Macrophages
title_full_unstemmed Preexisting Heterogeneity of Inducible Nitric Oxide Synthase Expression Drives Differential Growth of Mycobacterium tuberculosis in Macrophages
title_short Preexisting Heterogeneity of Inducible Nitric Oxide Synthase Expression Drives Differential Growth of Mycobacterium tuberculosis in Macrophages
title_sort preexisting heterogeneity of inducible nitric oxide synthase expression drives differential growth of mycobacterium tuberculosis in macrophages
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9600446/
https://www.ncbi.nlm.nih.gov/pubmed/36121153
http://dx.doi.org/10.1128/mbio.02251-22
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