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We are studying the genetic and molecular basis of virulence in members of the Mycobacterium tuberculosis complex.

Cow looking at researcher using laptop

Challenge

The Mycobacterium tuberculosis complex is comprised of a group of closely related bacteria with distinct host preferences. Species such as Mycobacterium bovis causes TB in animals, but has a wide host range. Species such as Mycobacterium tuberculosis and Mycobacterium africanum primarily cause TB in humans. Human TB is one of the top 10 causes of death from a single infectious agent and causes approximately 1.5 million deaths annually. The costs of control programmes of M. bovis infection in domestic livestock are prohibitively expensive and in LMIC M. bovis can represent a zoonotic risk. Unlike many other bacterial pathogens, members of the MTBC are highly genetically similar (>99% similar) and so we are trying to understand the genetic basis of host adaptation and virulence in both M. bovis and M. tuberculosis using a One Health approach. Despite the availability of many genome sequences we still do not understand the roles of many genes in virulence (e.g. virulence factors).

Cow looking at researcher using laptop

Solution

We are using whole genome approaches (Transposon insertion sequencing) to identify the gene required for survival in vivo. Additionally, we are using CRISPRi mediated gene silencing to investigate host pathogen interactions for selected gene targets. We are also utilising CRISPRi to determine target vulnerabilities for therapeutic agents for human tuberculosis. Through a better understanding of host:pathogen interactions in the two species we hope to generate novel therapeutics.

Partners

The work has been funded by several sources including; , , the  and 

Publications/Presentations

Title Publication Year
Mol Microbiol 2021
Frontiers in Veterinary Science 2021
Nature 2021
Front Microbiol 2021
Lancet Infect Dis 2020
Front Microbiol 2017
Br J Pharmacol 2017
J Biol Chem 2016
BMC Genomics 2015
Tuberculosis 2014
Acta Crystallogr Sect FStructural Biol Commun 2014
FEMS Microbiol Lett 2013
Environ Microbiol Rep 2012
J Microbiol Methods 2010
Microbiology 2010

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