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Deletion of N-acetylmuramyl-L-alanine amidases alters the host immune response to Mycobacterium tuberculosis infection

Peptidoglycan (PG), a heteropolysaccharide component of the mycobacterial cell wall can be shed during tuberculosis infection with immunomodulatory consequences. As such, changes in PG structure are expected to have important implications on disease progression and host responses during infection wi...

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Autores principales: Kieswetter, Nathan Scott, Ozturk, Mumin, Jones, Shelby-Sara, Senzani, Sibusiso, Chengalroyen, Melissa Dalcina, Brombacher, Frank, Kana, Bavesh, Guler, Reto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128173/
https://www.ncbi.nlm.nih.gov/pubmed/33980132
http://dx.doi.org/10.1080/21505594.2021.1914448
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author Kieswetter, Nathan Scott
Ozturk, Mumin
Jones, Shelby-Sara
Senzani, Sibusiso
Chengalroyen, Melissa Dalcina
Brombacher, Frank
Kana, Bavesh
Guler, Reto
author_facet Kieswetter, Nathan Scott
Ozturk, Mumin
Jones, Shelby-Sara
Senzani, Sibusiso
Chengalroyen, Melissa Dalcina
Brombacher, Frank
Kana, Bavesh
Guler, Reto
author_sort Kieswetter, Nathan Scott
collection PubMed
description Peptidoglycan (PG), a heteropolysaccharide component of the mycobacterial cell wall can be shed during tuberculosis infection with immunomodulatory consequences. As such, changes in PG structure are expected to have important implications on disease progression and host responses during infection with Mycobacterium tuberculosis. Mycobacterial amidases have important roles in remodeling of PG during cell division and are implicated in susceptibility to antibiotics. However, their role in modulating host immunity remains unknown. We assessed the bacterial burden and host immune responses to M. tuberculosis mutants defective for either one of two PG N-acetylmuramyl-L-alanine amidases, Ami1 and Ami4, in bone marrow-derived macrophages (BMDM) and C57BL/6 mice. In infected BMDM, the single deletion of both genes resulted in increased proinflammatory cytokine responses. In mice, infection with the Δami1 mutant led to differential induction of pro-inflammatory cytokines and chemokines, decreased cellular recruitment and reduced lung pathology during the acute phase of the infection. While increased proinflammatory cytokines production was observed in BMDM infected with the Δami4 mutant, these effects did not prevail in mice. Infection using the Δami1 and Δami4 Mtb mutants showed that these genes are dispensable for intracellular mycobacterial growth in macrophages and mycobacterial burden in mice. These findings suggest that both Ami1 and Ami4 in M. tuberculosis are not essential for mycobacterial growth within the host. In summary, we show that amidases are important for modulating host immunity during Mtb infection in murine macrophages and mice.
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spelling pubmed-81281732021-05-21 Deletion of N-acetylmuramyl-L-alanine amidases alters the host immune response to Mycobacterium tuberculosis infection Kieswetter, Nathan Scott Ozturk, Mumin Jones, Shelby-Sara Senzani, Sibusiso Chengalroyen, Melissa Dalcina Brombacher, Frank Kana, Bavesh Guler, Reto Virulence Research Paper Peptidoglycan (PG), a heteropolysaccharide component of the mycobacterial cell wall can be shed during tuberculosis infection with immunomodulatory consequences. As such, changes in PG structure are expected to have important implications on disease progression and host responses during infection with Mycobacterium tuberculosis. Mycobacterial amidases have important roles in remodeling of PG during cell division and are implicated in susceptibility to antibiotics. However, their role in modulating host immunity remains unknown. We assessed the bacterial burden and host immune responses to M. tuberculosis mutants defective for either one of two PG N-acetylmuramyl-L-alanine amidases, Ami1 and Ami4, in bone marrow-derived macrophages (BMDM) and C57BL/6 mice. In infected BMDM, the single deletion of both genes resulted in increased proinflammatory cytokine responses. In mice, infection with the Δami1 mutant led to differential induction of pro-inflammatory cytokines and chemokines, decreased cellular recruitment and reduced lung pathology during the acute phase of the infection. While increased proinflammatory cytokines production was observed in BMDM infected with the Δami4 mutant, these effects did not prevail in mice. Infection using the Δami1 and Δami4 Mtb mutants showed that these genes are dispensable for intracellular mycobacterial growth in macrophages and mycobacterial burden in mice. These findings suggest that both Ami1 and Ami4 in M. tuberculosis are not essential for mycobacterial growth within the host. In summary, we show that amidases are important for modulating host immunity during Mtb infection in murine macrophages and mice. Taylor & Francis 2021-05-13 /pmc/articles/PMC8128173/ /pubmed/33980132 http://dx.doi.org/10.1080/21505594.2021.1914448 Text en © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Paper
Kieswetter, Nathan Scott
Ozturk, Mumin
Jones, Shelby-Sara
Senzani, Sibusiso
Chengalroyen, Melissa Dalcina
Brombacher, Frank
Kana, Bavesh
Guler, Reto
Deletion of N-acetylmuramyl-L-alanine amidases alters the host immune response to Mycobacterium tuberculosis infection
title Deletion of N-acetylmuramyl-L-alanine amidases alters the host immune response to Mycobacterium tuberculosis infection
title_full Deletion of N-acetylmuramyl-L-alanine amidases alters the host immune response to Mycobacterium tuberculosis infection
title_fullStr Deletion of N-acetylmuramyl-L-alanine amidases alters the host immune response to Mycobacterium tuberculosis infection
title_full_unstemmed Deletion of N-acetylmuramyl-L-alanine amidases alters the host immune response to Mycobacterium tuberculosis infection
title_short Deletion of N-acetylmuramyl-L-alanine amidases alters the host immune response to Mycobacterium tuberculosis infection
title_sort deletion of n-acetylmuramyl-l-alanine amidases alters the host immune response to mycobacterium tuberculosis infection
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128173/
https://www.ncbi.nlm.nih.gov/pubmed/33980132
http://dx.doi.org/10.1080/21505594.2021.1914448
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