Associate Member, Michael Smith Laboratories
Howard Hughes Senior International Research Scholar

Research Summary

Resistance to standard antibiotic therapies is a growing health concern around the globe. Certain infections that are essentially untreatable have been identified in both hospital and community settings. The increasing frequency of drug resistance has been attributed to a combination of antibiotic over-prescription and societal and technologic changes that affect the transmission of drug-resistant organisms.

The ultimate goal of the research in our laboratory is the structure-based design of novel, therapeutically useful antibiotics and inhibitors of antibiotic-resistance mechanisms. To achieve this goal we use a combination of x-ray crystallography, molecular modelling, molecular docking and molecular biology in collaboration with medicinal chemistry to engineer drugs that specifically interact with and disable critical bacterial target proteins.


Ph.D. University of Alberta, 1990
B.Sc. University of Alberta, 1984

  1. Kumar NS, Amandoron EA, Cherkasov A, Brett Finlay B, Gong H, Jackson L, Kaur S, Lian T, Moreau A, Labrière C, Reiner NE, See RH, Strynadka NC, Thorson L, Wong EW, Worrall L, Zoraghi R, Young RN. Optimization and structure-activity relationships of a series of potent inhibitors of methicillin-resistant Staphylococcus aureus (MRSA) pyruvate kinase as novel antimicrobial agents. Bioorg Med Chem. 2012 Dec 15;20(24):7069-82.
  2. Lovering AL, Gretes MC, Safadi SS, Danel F, de Castro L, Page MG, Strynadka NC. Structural insights into the anti-methicillin-resistant Staphylococcus aureus (MRSA) activity of ceftobiprole. J Biol Chem. 2012 Sep 14;287(38):32096-102.
  3. Prehna G, Li Y, Stoynov N, Okon M, Vuckovic M, McIntosh LP, Foster LJ, Finlay BB, Strynadka NC. The zinc regulated antivirulence pathway of Salmonella is a multiprotein immunoglobulin adhesion system. J Biol Chem. 2012 Sep 21;287(39):32324-37.
  4. King DT, Worrall LJ, Gruninger R, Strynadka NC. New Delhi metallo-β-lactamase: structural insights into β-lactam recognition and inhibition. J Am Chem Soc. 2012 Jul 18;134(28):11362-5.
  5. Lovering AL, Safadi SS, Strynadka NC. Structural perspective of peptidoglycan biosynthesis and assembly. Annu Rev Biochem. 2012;81:451-78.
  6. Prehna G, Zhang G, Gong X, Duszyk M, Okon M, McIntosh LP, Weiner JH, Strynadka NC. A protein export pathway involving Escherichia coli porins.Structure. 2012 Jul 3;20(7):1154-66.
  7. Schur MJ, Lameignere E, Strynadka NC, Wakarchuk WW. Characterization of α2,3- and α2,6-sialyltransferases from Helicobacter acinonychis. Glycobiology. 2012 Jul;22(7):997-1006.
  8. Yu AC, Worrall LJ, Strynadka NC. Structural insight into the bacterial mucinase StcE essential to adhesion and immune evasion during enterohemorrhagic E. coli infection. Structure. 2012 Apr 4;20(4):707-17.
  9. Burkinshaw BJ, Prehna G, Worrall LJ, Strynadka NC. Structure of Salmonella effector protein SopB N-terminal domain in complex with host Rho GTPase Cdc42.J Biol Chem. 2012 Apr 13;287(16):13348-55.
  10. Axerio-Cilies P, See RH, Zoraghi R, Worral L, Lian T, Stoynov N, Jiang J, Kaur S, Jackson L, Gong H, Swayze R, Amandoron E, Kumar NS, Moreau A, Hsing M, Strynadka NC, McMaster WR, Finlay BB, Foster LJ, Young RN, Reiner NE, Cherkasov A. Cheminformatics-driven discovery of selective, nanomolar inhibitors for staphylococcal pyruvate kinase. ACS Chem Biol. 2012 Feb 17;7(2):350-9.
  11. Zoraghi R, Worrall L, See RH, Strangman W, Popplewell WL, Gong H, Samaai T, Swayze RD, Kaur S, Vuckovic M, Finlay BB, Brunham RC, McMaster WR, Davies-Coleman MT, Strynadka NC, Andersen RJ, Reiner NE. Methicillin-resistant Staphylococcus aureus (MRSA) pyruvate kinase as a target for bis-indole alkaloids with antibacterial activities. J Biol Chem. 2011 Dec 30;286(52):44716-25.
  12. Capyk JK, Casabon I, Gruninger R, Strynadka NC, Eltis LD. Activity of 3-ketosteroid 9α-hydroxylase (KshAB) indicates cholesterol side chain and ring degradation occur simultaneously in Mycobacterium tuberculosis. J Biol Chem. 2011 Nov 25;286(47):40717-24.
  13. Lin LY, Rakic B, Chiu CP, Lameignere E, Wakarchuk WW, Withers SG, Strynadka NC. Structure and mechanism of the lipooligosaccharide sialyltransferase from Neisseria meningitidis. J Biol Chem. 2011 Oct 28;286(43):37237-48.
  14. Lee HJ, Lairson LL, Rich JR, Lameignere E, Wakarchuk WW, Withers SG, Strynadka NC. Structural and kinetic analysis of substrate binding to the sialyltransferase Cst-II from Campylobacter jejuni. J Biol Chem. 2011 Oct 14;286(41):35922-32.
  15. King D, Strynadka N. Crystal structure of New Delhi metallo-β-lactamase reveals molecular basis for antibiotic resistance. Protein Sci. 2011 Sep;20(9):1484-91. doi: 10.1002/pro.697.
  16. Zoraghi R, See RH, Axerio-Cilies P, Kumar NS, Gong H, Moreau A, Hsing M, Kaur S, Swayze RD, Worrall L, Amandoron E, Lian T, Jackson L, Jiang J, Thorson L, Labriere C, Foster L, Brunham RC, McMaster WR, Finlay BB, Strynadka NC, Cherkasov A, Young RN, Reiner NE. Identification of pyruvate kinase in methicillin-resistant Staphylococcus aureus as a novel antimicrobial drug target. Antimicrob Agents Chemother. 2011 May;55(5):2042-53.
  17. Worrall LJ, Lameignere E, Strynadka NC. Structural overview of the bacterial injectisome. Curr Opin Microbiol. 2011 Feb;14(1):3-8.
  18. Babu M, Greenblatt JF, Emili A, Strynadka NC, Reithmeier RA, Moraes TF. Structure of a SLC26 anion transporter STAS domain in complex with acyl carrier protein: implications for E. coli YchM in fatty acid metabolism. Structure. 2010 Nov 10;18(11):1450-62.
  19. Sanowar S, Singh P, Pfuetzner RA, André I, Zheng H, Spreter T, Strynadka NC, Gonen T, Baker D, Goodlett DR, Miller SI. Interactions of the Transmembrane Polymeric Rings of the Salmonella enterica Serovar Typhimurium Type III Secretion System. MBio. 2010 Aug 3;1(3).
  20. Dresen C, Lin LY, D’Angelo I, Tocheva EI, Strynadka N, Eltis LD. A flavin-dependent monooxygenase from Mycobacterium tuberculosis involved in cholesterol catabolism. J Biol Chem. 2010 Jul 16;285(29):22264-75.
  21. Lovering AL, Lin LY, Sewell EW, Spreter T, Brown ED, Strynadka NC. Structure of the bacterial teichoic acid polymerase TagF provides insights into membrane association and catalysis. Nat Struct Mol Biol. 2010 May;17(5):582-9.
  22. Worrall LJ, Vuckovic M, Strynadka NC. Crystal structure of the C-terminal domain of the Salmonella type III secretion system export apparatus protein InvA. Protein Sci. 2010 May;19(5):1091-6.
  23. Reitinger S, Yu Y, Wicki J, Ludwiczek M, D’Angelo I, Baturin S, Okon M, Strynadka NC, Lutz S, Withers SG, McIntosh LP. Circular permutation of Bacillus circulans xylanase: a kinetic and structural study. Biochemistry. 2010 Mar 23;49(11):2464-74.
  24. Johnson JW, Gretes M, Goodfellow VJ, Marrone L, Heynen ML, Strynadka NC, Dmitrienko GI. Cyclobutanone analogues of beta-lactams revisited: insights into conformational requirements for inhibition of serine- and metallo-beta-lactamases. J Am Chem Soc. 2010 Mar 3;132(8):2558-60.
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