A Persistent Tuberculosis Outbreak in the UK Is Characterized by Hydrophobic fadB4 -Deficient Mycobacterium tuberculosis That Replicates Rapidly in Macrophages

Farzand, Robeena, Haigh, Richard D., Monk, Philip, Haldar, Pranabashis, Patel, Hemu, Pareek, Manish, Verma, Raman, Barer, Michael R., Woltmann, Gerrit, Ahyow, Lauren, Jagatia, Heena, Decker, Jonathan ORCID: 0000-0001-5904-7311, Mukamolova, Galina V., Cooper, Andrea M., Garton, Natalie J., O’Hare, Helen M. and Stallings, Christina L. (2022) A Persistent Tuberculosis Outbreak in the UK Is Characterized by Hydrophobic fadB4 -Deficient Mycobacterium tuberculosis That Replicates Rapidly in Macrophages. mBio, 13 (6). Art 02656. doi:10.1128/mbio.02656-22

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Abstract

The genetic diversity of Mycobacterium tuberculosis can influence disease severity and transmissibility. To better understand how this diversity influences individuals and communities, we phenotyped M. tuberculosis that was causing a persistent outbreak in the East Midlands, United Kingdom. Compared to nonoutbreak isolates, bacilli had higher lipid contents and more hydrophobic cell surfaces. In macrophage infection models, the bacteria increased more rapidly, provoked the enhanced accumulation of macrophage lipid droplets and enhanced the secretion of IL-1β. Natural deletions in fadB4, nrdB, and plcC distinguished the outbreak isolates from other lineage 3 isolates in the region. fadB4 is annotated with a putative role in cell envelope biosynthesis, so the loss of this gene has the potential to alter the interactions of bacteria with immune cells. Reintroduction of fadB4 to the outbreak strain led to a phenotype that more closely resembled those of nonoutbreak strains. The improved understanding of the microbiological characteristics and the corresponding genetic polymorphisms that associate with outbreaks have the potential to inform tuberculosis control.

Item Type:	Article
Article Type:	Article
Uncontrolled Keywords:	Mycobacterium tuberculosis: Genomes; Lung infection; Molecular epidemiology; Tuberculosis
Subjects:	Q Science > Q Science (General) Q Science > QR Microbiology
Divisions:	Schools and Research Institutes > School of Health and Social Care
Research Priority Areas:	Health, Life Sciences, Sport and Wellbeing
Depositing User:	Jonathan Decker
Date Deposited:	23 Aug 2023 22:11
Last Modified:	24 Aug 2023 21:11
URI:	https://eprints.glos.ac.uk/id/eprint/13062

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