Tissue specific diversification, virulence and immune response to Mycobacterium bovis BCG in a patient with an IFN-γ R1 deficiency

Summary: We characterized Mycobacterium bovis BCG isolates found in lung and brain samples from a previously vaccinated patient with IFNγR1 deficiency. The isolates collected displayed distinct genomic and phenotypic features consistent with host adaptation and associated changes in antibiotic susce...

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Autores principales:	Cecilia B. Korol, Shamira J. Shallom, Kriti Arora, Helena I. Boshoff, Alexandra F. Freeman, Alejandra King, Sonia Agrawal, Sean C. Daugherty, Timothy Jancel, Juraj Kabat, Sundar Ganesan, Marina N. Torrero, Elizabeth P. Sampaio, Clifton Barry, Steve M Holland, Hervé Tettelin, Sergio D Rosenzweig, Adrian M. Zelazny
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2020
Materias:	tuberculosis bcg antibiotic resistance immunodeficiency mendelian susceptibility to mycobacterial diseases interferon-γ Infectious and parasitic diseases RC109-216
Acceso en línea:	https://doaj.org/article/c389e6b7ad754220ad0f5defb0a60810
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spelling	oai:doaj.org-article:c389e6b7ad754220ad0f5defb0a608102021-11-17T14:21:59ZTissue specific diversification, virulence and immune response to Mycobacterium bovis BCG in a patient with an IFN-γ R1 deficiency2150-55942150-560810.1080/21505594.2020.1848108https://doaj.org/article/c389e6b7ad754220ad0f5defb0a608102020-12-01T00:00:00Zhttp://dx.doi.org/10.1080/21505594.2020.1848108https://doaj.org/toc/2150-5594https://doaj.org/toc/2150-5608Summary: We characterized Mycobacterium bovis BCG isolates found in lung and brain samples from a previously vaccinated patient with IFNγR1 deficiency. The isolates collected displayed distinct genomic and phenotypic features consistent with host adaptation and associated changes in antibiotic susceptibility and virulence traits. Background: We report a case of a patient with partial recessive IFNγR1 deficiency who developed disseminated BCG infection after neonatal vaccination (BCG-vaccine). Distinct M. bovis BCG-vaccine derived clinical strains were recovered from the patient’s lungs and brain. Methods: BCG strains were phenotypically (growth, antibiotic susceptibility, lipid) and genetically (whole genome sequencing) characterized. Mycobacteria cell infection models were used to assess apoptosis, necrosis, cytokine release, autophagy, and JAK-STAT signaling. Results: Clinical isolates BCG-brain and BCG-lung showed distinct Rv0667 rpoB mutations conferring high- and low-level rifampin resistance; the latter displayed clofazimine resistance through Rv0678 gene (MarR-like transcriptional regulator) mutations. BCG-brain and BCG-lung showed mutations in fadA2, fadE5, and mymA operon genes, respectively. Lipid profiles revealed reduced levels of PDIM in BCG-brain and BCG-lung and increased TAGs and Mycolic acid components in BCG-lung, compared to parent BCG-vaccine. In vitro infected cells showed that the BCG-lung induced a higher cytokine release, necrosis, and cell-associated bacterial load effect when compared to BCG-brain; conversely, both strains inhibited apoptosis and altered JAK-STAT signaling. Conclusions: During a chronic-disseminated BCG infection, BCG strains can evolve independently at different sites likely due to particular microenvironment features leading to differential antibiotic resistance, virulence traits resulting in dissimilar responses in different host tissues.Cecilia B. KorolShamira J. ShallomKriti AroraHelena I. BoshoffAlexandra F. FreemanAlejandra KingSonia AgrawalSean C. DaughertyTimothy JancelJuraj KabatSundar GanesanMarina N. TorreroElizabeth P. SampaioClifton BarrySteve M HollandHervé TettelinSergio D RosenzweigAdrian M. ZelaznyTaylor & Francis Grouparticletuberculosisbcgantibiotic resistanceimmunodeficiencymendelian susceptibility to mycobacterial diseasesinterferon-γInfectious and parasitic diseasesRC109-216ENVirulence, Vol 11, Iss 1, Pp 1656-1673 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	tuberculosis bcg antibiotic resistance immunodeficiency mendelian susceptibility to mycobacterial diseases interferon-γ Infectious and parasitic diseases RC109-216
spellingShingle	tuberculosis bcg antibiotic resistance immunodeficiency mendelian susceptibility to mycobacterial diseases interferon-γ Infectious and parasitic diseases RC109-216 Cecilia B. Korol Shamira J. Shallom Kriti Arora Helena I. Boshoff Alexandra F. Freeman Alejandra King Sonia Agrawal Sean C. Daugherty Timothy Jancel Juraj Kabat Sundar Ganesan Marina N. Torrero Elizabeth P. Sampaio Clifton Barry Steve M Holland Hervé Tettelin Sergio D Rosenzweig Adrian M. Zelazny Tissue specific diversification, virulence and immune response to Mycobacterium bovis BCG in a patient with an IFN-γ R1 deficiency
description	Summary: We characterized Mycobacterium bovis BCG isolates found in lung and brain samples from a previously vaccinated patient with IFNγR1 deficiency. The isolates collected displayed distinct genomic and phenotypic features consistent with host adaptation and associated changes in antibiotic susceptibility and virulence traits. Background: We report a case of a patient with partial recessive IFNγR1 deficiency who developed disseminated BCG infection after neonatal vaccination (BCG-vaccine). Distinct M. bovis BCG-vaccine derived clinical strains were recovered from the patient’s lungs and brain. Methods: BCG strains were phenotypically (growth, antibiotic susceptibility, lipid) and genetically (whole genome sequencing) characterized. Mycobacteria cell infection models were used to assess apoptosis, necrosis, cytokine release, autophagy, and JAK-STAT signaling. Results: Clinical isolates BCG-brain and BCG-lung showed distinct Rv0667 rpoB mutations conferring high- and low-level rifampin resistance; the latter displayed clofazimine resistance through Rv0678 gene (MarR-like transcriptional regulator) mutations. BCG-brain and BCG-lung showed mutations in fadA2, fadE5, and mymA operon genes, respectively. Lipid profiles revealed reduced levels of PDIM in BCG-brain and BCG-lung and increased TAGs and Mycolic acid components in BCG-lung, compared to parent BCG-vaccine. In vitro infected cells showed that the BCG-lung induced a higher cytokine release, necrosis, and cell-associated bacterial load effect when compared to BCG-brain; conversely, both strains inhibited apoptosis and altered JAK-STAT signaling. Conclusions: During a chronic-disseminated BCG infection, BCG strains can evolve independently at different sites likely due to particular microenvironment features leading to differential antibiotic resistance, virulence traits resulting in dissimilar responses in different host tissues.
format	article
author	Cecilia B. Korol Shamira J. Shallom Kriti Arora Helena I. Boshoff Alexandra F. Freeman Alejandra King Sonia Agrawal Sean C. Daugherty Timothy Jancel Juraj Kabat Sundar Ganesan Marina N. Torrero Elizabeth P. Sampaio Clifton Barry Steve M Holland Hervé Tettelin Sergio D Rosenzweig Adrian M. Zelazny
author_facet	Cecilia B. Korol Shamira J. Shallom Kriti Arora Helena I. Boshoff Alexandra F. Freeman Alejandra King Sonia Agrawal Sean C. Daugherty Timothy Jancel Juraj Kabat Sundar Ganesan Marina N. Torrero Elizabeth P. Sampaio Clifton Barry Steve M Holland Hervé Tettelin Sergio D Rosenzweig Adrian M. Zelazny
author_sort	Cecilia B. Korol
title	Tissue specific diversification, virulence and immune response to Mycobacterium bovis BCG in a patient with an IFN-γ R1 deficiency
title_short	Tissue specific diversification, virulence and immune response to Mycobacterium bovis BCG in a patient with an IFN-γ R1 deficiency
title_full	Tissue specific diversification, virulence and immune response to Mycobacterium bovis BCG in a patient with an IFN-γ R1 deficiency
title_fullStr	Tissue specific diversification, virulence and immune response to Mycobacterium bovis BCG in a patient with an IFN-γ R1 deficiency
title_full_unstemmed	Tissue specific diversification, virulence and immune response to Mycobacterium bovis BCG in a patient with an IFN-γ R1 deficiency
title_sort	tissue specific diversification, virulence and immune response to mycobacterium bovis bcg in a patient with an ifn-γ r1 deficiency
publisher	Taylor & Francis Group
publishDate	2020
url	https://doaj.org/article/c389e6b7ad754220ad0f5defb0a60810
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Tissue specific diversification, virulence and immune response to Mycobacterium bovis BCG in a patient with an IFN-γ R1 deficiency

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