Patricia Champion

Protein Transport in Mycobacterial Pathogens

Tuberculosis (TB) is the leading cause of death by infectious disease globally. It is estimated that one in three people worldwide are infected with Mycobacterium tuberculosis, the causative agent of TB. Although only 5-10% of infected people develop active disease, there are still approximately 1.4 million deaths annually (WHO). This burden of infection and disease is in part due to a lack of a viable vaccine that protects adults from pulmonary disease, the most common form of TB. To develop the vaccines and therapeutics needed to control the TB epidemic, we first need a better understanding of M. tuberculosis biology and the mechanisms it uses to cause disease. A key mechanism that bacteria use to promote their survival within the host is the targeted transport of bacterial proteins, small molecules or nucleic acids directly into the host (secretion). The long-term goal of my research program is to define the mechanisms of regulation and transport that promote protein secretion in Mycobacteria. To address this goal, we are focused on how the protein transport machinery is regulated, how it is assembled and how it functions in mycobacterial pathogens. We are interested in discovering: 1) how proteins that make up the machinery physically interact with each other and with the mycobacterial membranes 2) how protein substrates are selected for transport 3) the signals that regulate protein transport and how they are integrated by the mycobacterial cell 4) how genes and proteins associated with protein transport are regulated at the molecular level. To address these interests, we use an interdisciplinary approach including genetics, molecular biology, biochemistry and enzymology, and proteomics.

Publications

1. "EspM Is a Conserved Transcription Factor That Regulates Gene Expression in Response to the ESX-1 System" Sanchez, K.G.; Ferrell, M.J.; Chirakos, A.E.; Nicholson, K.R.; Abramovitch, R.B.; Champion, M.M.; Champion, P.A. mBio. 2020, 11(1), e02807-19. DOI: 10.1128/mBio.02807-19.  PMID: 32019792.
2. "A New ESX-1 Substrate in Mycobacterium marinum That Is Required for Hemolysis but Not Host Cell Lysis" Bosserman, R.E.; Nicholson, K.R.; Champion, M.M.; Champion, P.A. J. Bacteriol. 2019, 201(14), e00760-18. DOI: 10.1128/JB.00760-18. Print 2019 Jul 15.PMID: 30833360.
3. "Quantitative N-Terminal Footprinting of Pathogenic Mycobacteria Reveals Differential Protein Acetylation" Thompson, C.R.; Champion, M.M.; Champion, P.A. J. Proteome Res. 2018, 17(9), 3246-3258. DOI: 10.1021/acs.jproteome.8b00373. Epub 2018 Aug 16.PMID: 30080413.
4. "Esx paralogs are functionally equivalent to ESX-1 proteins but are dispensable for virulence in Mycobacterium marinum" Bosserman, R.E.; Thompson, C.R.; Nicholson, K.R.; Champion, P.A. J. Bacteriol. 2018, 200, e00726-17.