PIPages
Labs

Patricia A Champion

University of Notre Dame, IN·Microbiology & Immunology

Tuberculosis and related mycobacterial infections begin when the bacteria are swallowed by macrophages, the immune cells meant to destroy them. Instead of dying, the bacteria damage the compartment that holds them (the phagosome), escape into the cell's interior, and spread.

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Fields

Microbiology & Immunology

Biochemistry

Genetics

Topics

Mycobacterium tuberculosis

Mycobacterium marinum

type VII secretion

Grants
4 known grants, through Jul 2030

What they work on

  1. Identify how Mycobacterium marinum senses the detergent tyloxapol, combining unbiased genetic screens with hemolysis assays, and test whether tyloxapol suppresses ESX-1 membrane-breaking activity during macrophage infection.
  2. Map how tyloxapol changes mycobacterial protein export using quantitative proteomics, then trace the changes back to gene activity with qRT-PCR and promoter-reporter fusions, including the secreted protein EspE needed for phagosome escape.
  3. Determine which genes are required for membrane lysis at acidic pH, using targeted and unbiased genetics with immunoprecipitation-proteomics and ESX-1 functional assays in a large M. marinum mutant collection.
  4. Measure the full set of proteins secreted by M. marinum and M. tuberculosis at acidic pH to test whether the ESX-1 system swaps its cargo in response to the acidity of the host compartment.
  5. Test whether specific ESX-1 cargo proteins are switched on and needed during infection, using chemical blockers of phagosome acidification, differently activated macrophages, and animal infection models.
  6. Ask whether known virulence pathways, including those that modulate the host inflammasome alarm complex, protect M. marinum from bursting in the macrophage cytoplasm, using a lysis reporter adapted from Listeria monocytogenes.
  7. Run two complementary genetic screens during macrophage infection to discover new mycobacterial genes that prevent bacteriolysis and support survival in the host cell cytoplasm.
  8. Define the mycobacterial enzymes that add acetyl groups to protein N-termini and their substrate preferences, using enrichment strategies coupled to quantitative proteomics.
  9. Establish which virulence proteins are N-terminally acetylated and what the modification does, combining in vitro biochemical assays, targeted proteomics, and genetic manipulation of pathogenic mycobacteria.
  10. Link N-terminal acetylation to metabolism by growing mycobacteria on host-relevant carbon sources and comparing acetylation patterns, with proximity-dependent labeling to find regulators of the acetyltransferases.

More about the research

Work in this lab centers on the molecular machinery that makes this possible: how mycobacteria secrete proteins that break host membranes, how they tune that machinery to the chemistry of the environment they find themselves in, how they avoid being destroyed once inside the host cell, and how a chemical tag added to the front end of their proteins shapes all of this. Most experiments use Mycobacterium marinum, a fish-infecting relative that is an accepted laboratory stand-in for M. tuberculosis, alongside M. tuberculosis itself.

Why it matters

Mycobacterial infections, including tuberculosis, cause acute and chronic disease worldwide. The bacterial factors identified here — the ESX-1 secretion system and its cargo, pathways that keep bacteria intact inside host cells, and enzymes that chemically modify bacterial proteins — are candidate targets for new drugs and vaccines. The tyloxapol work could also clarify how a detergent used in thousands of mycobacterial experiments alters results, and why it has appeared protective in animal infections.

Known grants

From NIH and NSF research grants. Labs often have other funding we can't see.

pH-Dependent Switching of ESX-1 Substrates in Mycobacterial Pathogenesis

NIH · Aug 2025 – Jul 2030

Tyloxapol Inhibition of Mycobacterial Type VII Secretory Activity

NIH · Jun 2026 – May 2028

Identifying the mycobacterial genes controlling bacteriolysis in the macrophage cytoplasm

NIH · May 2024 – Mar 2027

Closest labs

Sabine Ehrt

Weill Medical College of Cornell University, NY·Microbiology & Immunology

Test whether mutations found repeatedly in patient strains in the metabolic enzymes PPGK, PEPCK and LDH change M. tuberculosis disease progression and antibiotic susceptibility, and identify the clinical pressures and interacting mutations that select them.

Yi Xu

Texas A&M University-College Station, TX·Microbiology & Immunology

Determine how important the secreted protein EsxA is to Streptococcus gallolyticus virulence, using bacterial mutants together with the cell culture and animal infection models established in the lab.

Anna Tischler

University of Minnesota, MN·Microbiology & Immunology

Build Mycobacterium tuberculosis strains whose phenylalanine-making enzymes can be switched on or off, and use them in macrophage and mouse infections to measure how much the bacterium needs this amino acid pathway during disease.

The school

University of Notre Dame: 19 labs on PI Pages, $346M a year on research, 277 research doctorates a year.

More about University of Notre Dame

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