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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Tissue specific diversification, virulence and immune response to Mycobacterium bovis BCG in a patient with an IFN-γ R1 deficiency
Virulence, Volume 11, No. 1, Year 2020
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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. © This work was authored as part of the Contributor’s official duties as an Employee of the United States Government and is therefore a work of the United States Government. In accordance with 17 U.S.C. 105, no copyright protection is available for such works under U.S. Law.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC7781554/bin/KVIR_A_1848108_SM7584.zip
Authors & Co-Authors
Shallom, Shamira J.
United States, Bethesda
National Institutes of Health Nih
Arora, Kriti
United States, Bethesda
National Institutes of Health Nih
Boshoff, Helena Ingrid M.
United States, Bethesda
National Institutes of Health Nih
Freeman, Alexandra F.
United States, Bethesda
National Institutes of Health Nih
King, Alejandra
Chile, Santiago
Hospital Dr. Luis Calvo Mackenna Hospital
Agrawal, Sonia
United States, Baltimore
University of Maryland School of Medicine
Daugherty, Sean C.
United States, Baltimore
University of Maryland School of Medicine
Kabát, Juraj
United States, Bethesda
National Institutes of Health Nih
Barry, Clifton Earl
United States, Bethesda
National Institutes of Health Nih
Holland, Steven M.
United States, Bethesda
National Institutes of Health Nih
Tettelin, Hervé
United States, Baltimore
University of Maryland School of Medicine
Rosenzweig, Sergio Damian
United States, Bethesda
National Institutes of Health Nih
Zelazny, Adrian M.
United States, Bethesda
National Institutes of Health Nih
Statistics
Citations: 2
Authors: 13
Affiliations: 3
Identifiers
Doi:
10.1080/21505594.2020.1848108
ISSN:
21505594
Research Areas
Cancer
Genetics And Genomics
Health System And Policy
Maternal And Child Health