Welcome to the
Dr. Brian K. Coombes’ laboratory is in the Department of Biochemistry and Biomedical Sciences and the Michael G. DeGroote Institute for Infectious Disease Research at McMaster University. We are affiliated with the Michael G. DeGroote School of Medicine a full-service research and teaching hospital located on the McMaster University campus. The McMaster campus is situated on 300 acres of nestled in the Niagara escarpment. Hamilton is 45 minutes from Toronto.
Dr. Brian K. Coombes’ laboratory is in the Department of Biochemistry and Biomedical Sciences and the Michael G. DeGroote Institute for Infectious Disease Research at McMaster University. We are affiliated with the Michael G. DeGroote School of Medicine a full-service research and teaching hospital located on the McMaster University campus. The McMaster campus is situated on 300 acres of property nestled in the Niagara escarpment. Hamilton is 45 minutes from Toronto.
HARNESSING IMMUNITY TO
Targeting two-component systems uncovers a small-molecule inhibitor of Salmonella virulence
Tsai, CN, NacNair, CR, Cao, MPT, Perry, JN, Magolan, J, Brown, ED, Coombes, BK. Cell Chemical Biology, May 2020
Evolution-guided discovery of antibiotics that inhibit peptidoglycan remodelling
Culp, E.J., Waglechner, N., Wang, W., Fiebig-Comyn, A.A., Hsu, Y., Koteva, K., Synchantha, D., Coombes, B.K., Van Nieuwenhze, M.S., Brun, Y.V., Wright, G.D. Nature, February 2020
Mimicking the human environment in mice reveals that inhibiting biotin biosynthesis is effective against antibiotic-resistant pathogens
Carfrae, L., MacNair, C.R., Brown, C.M., Tsai, C.N., Weber, B.S., Zlitni, S., Rao, V.N., Chun, J., Junop, M.S., Coombes, B.K., Brown, E.D Nature Microbiology, January 2020
The Unique Lifestyle of Crohn's Disease-Associated Adherent-Invasive Escherichia coli
Shaler, C.R., Elhenawy, W., Coombes, B.K. Journal of Molecular Biology. April 25, 2019
Duodenal bacterial proteolytic activity determines sensitivity to dietary antigen through protease-activated receptor-2
Caminero, A., et al. Nature Communications, 10(1): 1198
Endocytosis of commensal antigens by intestinal epithelial cells regulates mucosal T cell homeostasis
Ladinsky, M.S., et al. Science, 8:363
The role of the host in driving phenotypic heterogeneity in Salmonella
Tsai, C.N. and Coombes B.K. Trends in Microbiology, February 2019
Host-Specific Adaptive Diversification of Crohn’s Disease-Associated Adherent-Invasive Escherichia coli
Elhenawy, W., Tsai, C.N., Coombes, B.K. Cell Host & Microbe
A macrophage-based screen identifies antibacterial compounds selective for intracellular SalmonellaTyphimurium
Ellis, M.J., Tsai, C.N., Johnson, J.W., French, S., Elhenawy, W., Porwollik, S., Andrews-Polymenis, H., McClelland, M., Magolan, J., Coombes, B.K., Brown, E.D. Nature Communications
Antibiotics potentiate adherent-invasive E. coli infection and expansion
Oberc, A.M., Fiebig-Comyn, A.A., Tsai, C.N., Elhenawy, W., Coombes, B.K. 2019. Inflammatory Bowel Diseases. 25(4):711-721
Regulatory Evolution Drives Evasion of Host Inflammasomes by Salmonella Typhimurium
Ilyas, B., Mulder, D.T., Little, D.J., Elhenawy, W., Banda, M.M., Perez-Morales, D., Tsai, C.N., Chau, N.Y.E., Bustamante, V.H., Coombes, B.K. 2018. Cell Reports.
Functional diversification of the NleG effector family in enterohemorrhagic Escherichia coli
Valleau, D., Little, D.J., Borek, D., Skarina, T., Quaile, A.T., Di Leo, R., Houliston, S., Lemak, A., Arrowsmith, C.H., Coombes, B.K., Savchenko, A. 2018. PNAS.
Molecular basis for CesT recognition of type 3 secretion effectors in enteropathogenic E. coli
Little, D., Coombes, B.K. 2018 PLoS Pathogens. 14(8):e1007224
The transcriptional regulator SsrB is involved in a molecular switch controlling virulence lifestyles of Salmonella
Perez-Morales, D., Banda, M.M., Chau, N.Y.E., Salgado, H., Martinez-Flores, I., Ibarra, A., Ilyas, B., Coombes, B.K., Bustamante, V.H. 2017. PLoS Pathogens. 13(7): e1006497.
Pentamidine sensitizes Gram-negative pathogens to antibiotics and overcomes acquired colistin resistance
Stokes, J.M., MacNair, C.R., Ilyas, B., French, S., Cote, J, Bouwman, C., Farha, M.A., Sieron, A.O., Whitfield, C., Coombes, B.K., Brown, E.D. 2017. Nature Microbiology. 2:17028. 1-8.
Acute infectious gastroenteritis potentiates a Crohn's disease pathobiont to fuel ongoing inflammation in the post-infectious period
Small, C.N., Xing, L., McPhee, J.B., Law, H.T., Coombes, B.K. PLoS Pathogens. 1-20.
Bacterial Evolution: Making a host-adapted bacterum
Coombes, B.K. Nature Microbiology. doi:10.1038/NMICROBIOL.2016.10
CXCL9 contributes to antimicrobial protection of the gut during Citrobacter rodentium infection independent of chemokine-receptor signaling
Reid-Yu, S.A., Tuinema, B.R., Small, C.N., Xing, L., Coombes, B.K. PLoS Pathogens. 11(2):e1004648
Salmonella evades D-amino acid oxidase to promote infection in neutrophils
Tuinema, B.R., Reid-Yu, S.A., Coombes, BK. mBio. 5(6):e01886-14.
Aspergillomarasmine A overcomes metallo-beta-lactamase antibiotic resistance
King, A.M., Reid-Yu, SA, Wang, W., King, DT., De Pascale, G., Strynadka, NC., Walsh, TR., Coombes, BK., Wright, GD. Nature (from the cover). June 26, 2014.
Persistent infection with Crohn’s disease-associated adherent-invasive Escherichia coli leads to chronic inflammation and intestinal fibrosis
Small, C.N., Reid-Yu, S.A., McPhee, J.B., Coombes, B.K. Nature Communications. DOI: 10.1038/ncomms2957.
Infection Biology: cheats never prosper
Mulder DT and Coombes BK. Nature. 494:321-322.
GogB is an anti-inflammatory effector that limits tissue damage during Salmonella infection through interaction with human FBXO22 and Skp1.
Pilar AV, Reid-Yu SA, Cooper CA, Mulder DT, Coombes BK. PLoS Pathogens. 8(6):e1002773.
A draft genome of Yersinia pestis from victims of the Black Death.
Bos, K., Schuenemann, VJ., Golding, GB., et al. Nature. 478:506-510.
Combinations of antibiotics and non-antibiotic drugs enhance antimicrobial efficacy.
Ejim L, Farha MA, Falconer SB, Wildenhain J, Coombes BK, Tyers M, Brown ED, Wright GD. Nature Chemical Biology. 7(6): 348-350.
Identification of the regulatory logic controlling Salmonella pathoadaptation by the SsrA-SsrB two-component system.
Tomljenovic-Berube, A.M., Mulder, D.T., Whiteside, M.D., Brinkman, F.S., Coombes, B.K. PLoS Genetics. Mar 12; 6(3):e1000875.
Pathogenic adaptation of intracellular bacteria by rewiring an ancestral cis-regulatory input function.
Osborne, S.E., Walthers, D., Duong, N., Lowden, M.J., Tomljenovic, A.M., Wickham, M.E., Silphaduang, U., Waller, R.F., Kenney, L.J., Coombes, B.K. Proc Natl Acad Sci USA. 106: 3982–3987.
A complete listing of the lab's publications can be found on PubMed