Pathogenic mycobacteria include microbes that cause the human disease, Tuberculosis, and other chronic human infections. Several of the mechanisms used by Mycobacterium tuberculosis to cause disease are shared with environmental bacteria that cause chronic infections. We are interested in understanding the shared molecular mechanisms used by pathogenic mycobacteria to cause disease.
During infection, the mycobacterial pathogens manipulate the host cell to avoid detection by the immune response, and to create a niche that favors replication and persistence. One of the major ways that mycobacterial pathogens manipulate the host is through the secretion of bacterial proteins. The ESX-1 (ESAT-6 System-1) system transports protein virulence factors that are required for mycobacterial pathogenesis. While there are many proteins known to play a role in ESX-1 protein secretion, the way the majority of these proteins function is unclear. Moreover, the pathways regulating the process of proteins secretion are not well understood. We are interested in 1) identifying novel components and substrates of the ESX-1 system, 2) determining how components of this complex secretion machine function to select and transport protein substrates during infection and 3) defining regulatory pathways that fine tune the process of secretion.
To do so, we use Mycobacterium marinum and Mycobacterium tuberculosis. M. marinum is a non-tuberculous mycobacterial species (NTM) that is related to M. tb, that causes a tuberculosis-like infection in poikilothermic fish, but rarely causes serious disease in humans. Despite the differences between these two pathogens, the ESX-1 system is functionally conserved. We study the molecular biology of mycobacterial protein secretion using genetic, proteomic and biochemical approaches to better understand mycobacterial pathogenesis. We use both amoebae and macrophage infection models. Understanding the mechanisms used by pathogenic mycobacteria to cause disease will inform future strategies to combat mycobacterial disease, and provide fundamental insight to the process of mycobacterial protein secretion.
WhiB6 regulation of ESX-1 gene expression is controlled by a negative feedback loop in Mycobacterium marinum.
Rachel E. Bosserman, Tiffany T. Nguyen, Kevin G. Sanchez, Alexandra E. Chirakos, Micah J. Ferrell, Cristal R. Thompson, Matthew M. Champion, Robert B. Abramovitch, and Patricia A. Champion.
PNAS, 2017; doi:10.1073/pnas.1710167114
Esx Systems and the Mycobacterial Cell Envelope: What's the Connection?
Bosserman RE, Champion PA.
Journal of Bacteriology. 2017; 199(17).
A Nonsense Mutation in Mycobacterium marinum That Is Suppressible by a Novel Mechanism.
Williams EA, Mba Medie F, Bosserman RE, Johnson BK, Reyna C, Ferrell MJ, Champion MM, Abramovitch RB, Champion PA.
Infection and Immunity. 2017; 85(2).
Rational engineering of a virulence gene from Mycobacterium tuberculosis facilitates proteomic analysis of a natural protein N-terminus.
Reyna C, Mba Medie F, Champion MM, Champion PA.
Scientific Reports. 2016; 6:33265.
Correlation of phenotypic profiles using targeted proteomics identifies mycobacterial esx-1 substrates.
Champion MM, Williams EA, Pinapati RS, Champion PA.
Journal of Proteome Research. 2014; 13(11):5151-64.
Click here for a complete listing of our publications: www.ncbi.nlm.nih.gov/sites/myncbi/patricia.champion.1/bibliography/41154650/public/?sort=date&direction= descending