Natural Products in Antibiotic Discovery

  • Fern R. McSorley
  • Jarrod W. Johnson
  • Gerard D. WrightEmail author
Part of the Emerging Infectious Diseases of the 21st Century book series (EIDC)


The development of antibiotics for human chemotherapy is one of the most important medical advances of the twentieth century; the vast majority of antibiotics in clinical use are microbial natural products or their semisynthetic derivatives. Pharmaceutical companies have been unsuccessful in identifying new antibiotics by screening libraries of synthetic compounds, because their chemical collections lack suitable chemical diversity tuned to entry into and retention by bacterial cells. Since natural products possess more of the physiochemical properties required for in vivo activity, there is a growing movement toward a return to these compounds for antibiotic discovery. Traditional screening methods for new antibiotics are plagued by the rediscovery of known compounds; consequently, new strategies are required to find new activity. For example, using medicinal chemistry to revisit discarded or underexplored scaffolds, or screening for adjuvants (e.g., inhibitors of resistance enzymes) can breathe new life into old antibiotics. The chemical diversity of antibiotics can also be increased by exploring new sources for antibiotic-producing organisms, by employing synthetic biology approaches using known scaffolds, and by mining genomes for silent or cryptic biosynthetic clusters.


  1. 1.
    Borchardt JK. The beginnings of drug therapy: ancient Mesopotamian medicine. Drug News Perspect. 2002;15(3):187–92.PubMedGoogle Scholar
  2. 2.
    Scurlock J. Sourcebook for ancient Mesopotamian medicine: Society of Biblical Literature; 2014.Google Scholar
  3. 3.
    Cragg GM, Newman DJ. Natural products: a continuing source of novel drug leads. Biochim Biophys Acta. 2013;1830(6):3670–95.PubMedPubMedCentralGoogle Scholar
  4. 4.
    Huang KC. The pharmacology of chinese herbs. 2nd ed. Boca Raton: CRC Press; 1999.Google Scholar
  5. 5.
    Kapoor LD. CRC handbook of ayurvedic medicinal plants. Boca Raton: CRC Press; 1990.Google Scholar
  6. 6.
    Sertuerner F. Ueber das Morphium, eine neue salzfähige Grundlage, und die Mekonsäure, als Hauptbestandtheile des Opiums. Ann Phys (Berl). 1817;55(1):56–89.Google Scholar
  7. 7.
    Newman DJ, Cragg GM. Chapter 1 Natural products as drugs and leads to drugs: the historical perspective. Natural Product Chemistry for Drug Discovery: The Royal Society of Chemistry; 2009. p. 3–27.Google Scholar
  8. 8.
    Fleming A. On the antibacterial action of cultures of a Penicillium, with special reference to their use in the isolation of B. influenzæ. Br J Exp Pathol. 1929;10(3):226–36.PubMedCentralGoogle Scholar
  9. 9.
    Zasloff M. Antimicrobial peptides of multicellular organisms. Nature. 2002;415(6870):389–95.PubMedGoogle Scholar
  10. 10.
    Newman DJ, Cragg GM. Natural products as sources of new drugs from 1981 to 2014. J Nat Prod. 2016;79(3):629–61.PubMedGoogle Scholar
  11. 11.
    Walsh CT, Wencewicz T. Antibiotics: challenges mechanisms opportunities. Washington, DC: ASM Press; 2016.Google Scholar
  12. 12.
    Brown ED, Wright GD. Antibacterial drug discovery in the resistance era. Nature. 2016;529(7586):336–43.PubMedGoogle Scholar
  13. 13.
    Ehrlich P, Hata S. Die experimentelle Chemotherapie der Spirillosen:(Syphilis, Rückfallfieber, Hühnerspirillose, Frambösie). Wiesbaden: Springer; 1910.Google Scholar
  14. 14.
    Aminov RI. A brief history of the antibiotic era: lessons learned and challenges for the future. Front Microbiol. 2010;1:134.PubMedPubMedCentralGoogle Scholar
  15. 15.
    Mahoney JF, Arnold RC, Harris A. Penicillin treatment of early syphilis-a preliminary report. Am J Public Health Nations Health. 1943;33(12):1387–91.PubMedPubMedCentralGoogle Scholar
  16. 16.
    Lewis K. Platforms for antibiotic discovery. Nat Rev Drug Discov. 2013;12(5):371–87.PubMedGoogle Scholar
  17. 17.
    Domagk G. Ein Beitrag zur Chemotherapie der bakteriellen Infektionen. Dtsch Med Wochenschr. 1935;61(7):250–3.Google Scholar
  18. 18.
    Lewis K. Antibiotics: recover the lost art of drug discovery. Nature. 2012;485(7399):439–40.PubMedGoogle Scholar
  19. 19.
    Wright GD. Opportunities for natural products in 21st century antibiotic discovery. Nat Prod Rep. 2017;34(7):694–701.PubMedGoogle Scholar
  20. 20.
    Tipper DJ, Strominger JL. Mechanism of action of penicillins: a proposal based on their structural similarity to acyl-D-alanyl-D-alanine. Proc Natl Acad Sci U S A. 1965;54(4):1133–41.PubMedPubMedCentralGoogle Scholar
  21. 21.
    Rolinson GD. Forty years of beta-lactam research. J Antimicrob Chemother. 1998;41(6):589–603.PubMedGoogle Scholar
  22. 22.
    Drawz SM, Papp-Wallace KM, Bonomo RA. New β-lactamase inhibitors: a therapeutic renaissance in an MDR world. Antimicrob Agents Chemother. 2014;58(4):1835–46.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Wang DY, Abboud MI, Markoulides MS, Brem J, Schofield CJ. The road to avibactam: the first clinically useful non-β-lactam working somewhat like a β-lactam. Future Med Chem. 2016;8(10):1063–84.PubMedGoogle Scholar
  24. 24.
    Castanheira M, Rhomberg PR, Flamm RK, Jones RN. Effect of the β-lactamase inhibitor Vaborbactam combined with Meropenem against serine carbapenemase-producing Enterbacteriaceae. Antimicrob Agents Chemother. 2016;60(9):5454–8.PubMedPubMedCentralGoogle Scholar
  25. 25.
    Sykes RB, Cimarusti CM, Bonner DP, Bush K, Floyd DM, Georgopapadakou NH, Koster WM, Liu WC, Parker WL, Principe PA, Rathnum ML, Slusarchyk WA, Trejo WH, Wells JS. Monocyclic beta-lactam antibiotics produced by bacteria. Nature. 1981;291(5815):489–91.PubMedGoogle Scholar
  26. 26.
    Sykes RB, Bonner DP, Bush K, Georgopapadakou NH. Azthreonam (SQ26,776), a synthetic monobactam specifically active against aerobic gram-negative bacteria. Antimicrob Agents Chemother. 1982;21(1):85–92.PubMedPubMedCentralGoogle Scholar
  27. 27.
    Waksman SA, Reilly HC, Johnston DB. Isolation of streptomycin-producing strains of Streptomyces griseus. J Bacteriol. 1946;52(3):393–7.PubMedPubMedCentralGoogle Scholar
  28. 28.
    Umezawa H. Kanamycin: its discovery. Ann N Y Acad Sci. 1958;76(2):20–6.PubMedGoogle Scholar
  29. 29.
    Weinstein MJ, Luedemann GM, Oden EM, Wagman GH, Rosselet JA, Coniglio CT, Charney W, Herzog HL, Black J. Gentamicin, a new antibiotic complex from micromonospora. J Med Chem. 1963;6(4):463.PubMedGoogle Scholar
  30. 30.
    Garneau-Tsodikova S, Labby KJ. Mechanisms of resistance to aminoglycoside antibiotics: overview and perspectives. Medchemcomm. 2016;7(1):11–27.PubMedGoogle Scholar
  31. 31.
    Katz L, Ashley GW. Translation and protein synthesis: macrolides. Chem Rev. 2005;105(2):499–528.PubMedGoogle Scholar
  32. 32.
    Gomes C, Martinez-Puchol S, Palma N, Horna G, Ruiz-Roldán L, Pons MJ, Ruiz J. Macrolide resistance mechanisms in Enterobacteriaceae: focus on azithromycin. Crit Rev Microbiol. 2017;43(1):1–30.PubMedGoogle Scholar
  33. 33.
    Wright PM, Seiple IB, Myers AG. The evolving role of chemical synthesis in antibacterial drug discovery. Angew Chem Int Ed Engl. 2014;53(34):8840–69.PubMedPubMedCentralGoogle Scholar
  34. 34.
    Yang W, Moore IF, Koteva KP, Bareich DC, Hughes DW, Wright GD. TetX is a flavin-dependent monooxygenase conferring resistance to tetracycline antibiotics. J Biol Chem. 2004;279(50):52346–52.PubMedGoogle Scholar
  35. 35.
    Floss HG, Yu TW. Rifamycin-mode of action, resistance, and biosynthesis. Chem Rev. 2005;105(2):621–32.PubMedGoogle Scholar
  36. 36.
    Goldstein BP. Resistance to rifampicin: a review. J Antibiot (Tokyo). 2014;67(9):625–30.Google Scholar
  37. 37.
    Bugg TD, Wright GD, Dutka-Malen, S, Arthur, M, Courvalin, P, Walsh CT. Molecular basis for vancomycin resistance in Enterococcus faecium BM4147: biosynthesis of a depsipeptide peptidoglycan precursor by vancomycin resistance proteins VanH and VanA. Biochem. 1991; 30(43):10408–10415.Google Scholar
  38. 38.
    Kirst HA, Thompson DG, Nicas TI. Historical yearly usage of vancomycin. Antimicrob Agents Chemother. 1998;42(5):1303–4.PubMedPubMedCentralGoogle Scholar
  39. 39.
    Kahne D, Leimkuhler C, Lu W, Walsh C. Glycopeptide and lipoglycopeptide antibiotics. Chem Rev. 2005;105(2):425–48.PubMedGoogle Scholar
  40. 40.
    Mukhtar TA, Wright GD. Streptogramins, oxazolidnones, and other inhibitors of bacgerial protein synthesis. Chem Rev. 2005;105(2):529–42.PubMedGoogle Scholar
  41. 41.
    Wilson DN. The A-Z of bacterial translation inhibitors. Crit Rev Biochem Mol Biol. 2009;44(6):393–433.PubMedGoogle Scholar
  42. 42.
    Allington DR, Rivey MP. Quinupristin/dalfopristin: a therapeutic review. Clin Ther. 2001;23(1):24–44.PubMedGoogle Scholar
  43. 43.
    Eisenstein BI, Oleson FB Jr, Baltz RH. Daptomycin: from the mountain to the clinic, with essential help from Francis Tally, MD. Clin Infect Dis. 2010;50(1):S10–5.PubMedGoogle Scholar
  44. 44.
    Taylor SD, Palmer M. The action mechanism of daptomycin. Bioorg Med Chem. 2016;24(24):6253–68.PubMedGoogle Scholar
  45. 45.
    Ordooei Javan A, Shokouhi S, Sahraei Z. A review on colisten nephrotoxicity. Eur J Clin Pharmacol. 2015;71(7):801–10.PubMedGoogle Scholar
  46. 46.
    Velkov T, Thompson PE, Nation RL, Li J. Structure-activity relationships of polymyxin antibiotics. J Med Chem. 2010;53(5):1898–916.PubMedPubMedCentralGoogle Scholar
  47. 47.
    Yu Z, Quin W, Lin J, Fang S, Qiu J. Antibacterial mechanisms of polymyxin and bacterial resistance. Biomed Res Int. 2015;2015:679109.PubMedPubMedCentralGoogle Scholar
  48. 48.
    Srinivas P, Rivard K. Polymyxin resistance in gram-negative pathogens. Curr Infect Dis Rep. 2017;19(11):38.PubMedGoogle Scholar
  49. 49.
    Miller WR, Bayer AS, Arias CA. Mechanism of action and resistance to daptomycin in Staphylococcus aureus and Enterocci. Cold Spring Harb Perspect Med. 2016;6(11):a026997.PubMedPubMedCentralGoogle Scholar
  50. 50.
    Novak R. Are pleuromutilin antibiotics finally fit for human use? Ann N Y Acad Sci. 2011;1241:71–81.PubMedGoogle Scholar
  51. 51.
    Dinos GP, Athanassopoulos CM, Missiri DA, Giannopoulou PC, Vlachogiannis IA, Papadopoulos GE, Papaioannou D, Kalpaxis DL. Chloramphenicol derivatives as antibacterial and anticancer agents: historic problems and current solutions. Antibiotics (Basel). 2016;5(2):20.Google Scholar
  52. 52.
    Silver LL. Fosfomycin: mechanism and resistance. Cold Spring Harb Perpect Med. 2017;7(2):a025262.Google Scholar
  53. 53.
    Fidaxomicin. A novel agent for the treatment of Clostridium difficile infection. Can J Infect Dis Med Microbiol. 2015;26(6):305–12.Google Scholar
  54. 54.
    Payne DJ, Gwynn MN, Holmes DJ, Pompliano DL. Drugs for bad bugs: confronting the challenges of antibacterial discovery. Nat Rev Drug Discov. 2007;6(1):29–40.PubMedGoogle Scholar
  55. 55.
    Tommasi R, Brown DG, Walkup GK, Manchester JI, Miller AA. ESKAPEing the labyrinth of antibacterial discovery. Nat Rev Drug Discov. 2015;14(8):529–42.PubMedGoogle Scholar
  56. 56.
    Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rec. 2001;46(1–3):3–26.Google Scholar
  57. 57.
    O'Shea R, Moser HE. Physicochemical properties of antibacterial compounds: implications for drug discovery. J Med Chem. 2008;51(10):2871–8.PubMedGoogle Scholar
  58. 58.
    Mugumbate G, Overington JP. The relationship between target-class and the physiochemical properties of antibacterial drugs. Bioorg Med Chem. 2015;23(16):5218–24.PubMedPubMedCentralGoogle Scholar
  59. 59.
    Brown DG, Tl M-D, Gagnon MM, Tommasi R. Trends and exceptions of physical properties on antibacterial activity for Gram-positive and Gram-negative pathogens. J Med Chem. 2014;57(23):10144–61.PubMedGoogle Scholar
  60. 60.
    Ganesan A. The impacet of natural product upon modern drug discovery. Curr Opin Chem Biol. 2008;12(3):306–17.PubMedGoogle Scholar
  61. 61.
    Harvey AL, Edrada-Ebel R, Quinn RJ. The re-emergene of natural products for drug discovery in the genomics era. Nat Rev Drug Discov. 2015;14(2):111–29.PubMedGoogle Scholar
  62. 62.
    Lovering F, Bikker J, Humblet C. Escape from flatland: increasing saturation as an approach to improving clinial success. J Med Chem. 2009;52(21):6752–6.PubMedGoogle Scholar
  63. 63.
    Lovering F. Escape from Flatland 2: complexity and promiscuity. Med Chem Commun. 2013;4(3):515–9.Google Scholar
  64. 64.
    Buggs CW. Ten years after streptomycin; past and current practice in antibiotic therapy. J Natl Med Assoc. 1957;49(3):142–9.PubMedPubMedCentralGoogle Scholar
  65. 65.
    Baltz RH. Antimicrobials from actinomycetes: back to the future. Microbe. 2007;2(3):125.Google Scholar
  66. 66.
    Katz L, Baltz RH. Natural product discovery: past, present, and future. J Ind Microbiol Biotechnol. 2016;43(2–3):155–76.PubMedGoogle Scholar
  67. 67.
    Chang B-C, Wang S-J. The impact of patent eligibility on biotech patents: a flow chart for determining patent eligibility and an immune therapy case study. Hum Vaccin Immunother. 2015;11(3):789–94.PubMedPubMedCentralGoogle Scholar
  68. 68.
    Challis GL, Hopwood DA. Synergy and contingency as driving forces for the evolution of multiple secondary metabolite production by Streptomyces species. Proc Natl Acad Sci U S A. 2003;100(2):14555–61.PubMedPubMedCentralGoogle Scholar
  69. 69.
    Wright GD. Antibiotic adjuvants: rescuing antibiotics from resistance. Trends Microbiol. 2016;24(11):862–71.PubMedGoogle Scholar
  70. 70.
    Melander RJ, Melander C. The challenge of overcoming antibiotic resistance: an adjuvant approach? ACS Infect Dis. 2017;3(8):559–63.PubMedPubMedCentralGoogle Scholar
  71. 71.
    Cox G, Siron A, King AM, De Pascale G, Pawlowski AC, Koteva K, Wright GD. Cell Chem Biol. 2017;24(1):98–109.PubMedGoogle Scholar
  72. 72.
    King AM, Reid-Yu SA, Wang W, King DT, De Pascale G, Strynadka NC, Walsh TR, Coombes BK, Wright GD. Aspergillomarasmine A overcomes metallo-β-lacamse antibiotic resistance. Nature. 2014;510(7506):503–6.PubMedPubMedCentralGoogle Scholar
  73. 73.
    Stermitz FR, Lorenz P, Tawara JN, Zenewicz LA, Lewis K. Synergy in a medicinal plant: antimicrobial action of berberine potentiated by 5′-methoxyhydnocarpin, a multidrug pump inhibitor. Proc Natl Acad Sci U S A. 2000;97(4):1433–7.PubMedPubMedCentralGoogle Scholar
  74. 74.
    Malik M, Li L, Zhao X, Kerns RJ, Berger JM, Drlica K. Lethal synergy involving bicyclomycin: an approach for reviving old antibiotics. J Antimicrob Chemother. 2014;69(12):3227–35.PubMedPubMedCentralGoogle Scholar
  75. 75.
    Ling LL, Schneider T, Peoples AJ, Spoering AL, Engels I, Conlon BP, Mueller A, Schäberle TF, Hughes DE, Epstein S, Jones M, Lazarides L, Steadman VA, Cohen DR, Felix CR, Fetterman KA, Millet WP, Nitti AG, Zullo AM, Chen X, Lewis K. A new antibiotic kills pathogens without detectable resistance. Nature. 2015;517(7535):455–9.PubMedGoogle Scholar
  76. 76.
    Charlop-Powers Z, Owen JG, Reddy BV, Ternei MA, Guimarães DO, de Frias UA, Pupo MT, Seepe P, Feng Z, Brady SF. Global biogeographical sampling of bacterial secondary metabolism. elife. 2015;4:e05048.PubMedPubMedCentralGoogle Scholar
  77. 77.
    Masschelein J, Jenner M, Challis GL. Antibiotics from Gram-negative bacteria: a comprehensive overview and selected biosynthetic highlights. Nat Prod Rep. 2017;34(7):712–83.PubMedGoogle Scholar
  78. 78.
    Hermann J, Fayad AA, Müller R. Natural products from myxobacteria: novel metabolites and bioactivities. Nat Prod Rep. 2017;34(2):135–60.Google Scholar
  79. 79.
    Lok C. Mining the microbial dark matter. Nature. 2015;522(7556):270–3.PubMedGoogle Scholar
  80. 80.
    Nichols D, Cahoon N, Trakhtenber EM, Pham L, Mehta A, Belanger A, Kanigan T, Lewis K, Epstein SS. Use of ichip for high-throughput in situ cultivation of “uncultivable” microbial species. Appl Environ Microbiol. 2010;76(8):2445–50.PubMedPubMedCentralGoogle Scholar
  81. 81.
    Blin K, Wolf T, Chevrette MG, Lu X, Schwalen CJ, Kautsar SA, Suarez Duran HG, de Los Santos ELC, Kim H, Nave M, Dickschat JS, Mitchell DA, Shelest E, Breitling R, Takano E, Sy L, Webe T, Medema MH. antiSMASH 4.0-improvements in chemistry predictions and gene cluster boundary identification. Nucleic Acids Res. 2017;45(W1):W36–41. Scholar
  82. 82.
    Ibrahim A, Yang L, Johnston C, Liu X, Ma B, Magarvey NA. Dereplicating nonribosomal peptides using an informatic search algorithm for natural products (iSNAP) discovery. Proc Natl Acad Sci U S A. 2012;109(47):19196–201.PubMedPubMedCentralGoogle Scholar
  83. 83.
    Johnston CW, Skinnider MA, Wyatt MA, Li X, Ranieri MR, Yang L, Zecehl DL, Ma B, Magarvey NA. An automated Gencomes-to-Natural Products platform (GNP) for the discovery of modular natural products. Nat Commun. 2015;8:8421.Google Scholar
  84. 84.
    Medema MH, Osbourn A. Computational genomic identification and functional reconstitution of plant natural product biosynthetic pathways. Nat Prod Rep. 2016;33(8):951–62.PubMedPubMedCentralGoogle Scholar
  85. 85.
    Skinnifer MA, Merwin NJ, Johnston CW, Magarvey NA. PRISM 3: expanded prediction of natural product chemical structures from microbial genomes. Nucleic Acids Res. 2017;45(W1):W49–54.Google Scholar
  86. 86.
    Johnston CW, Skinnider MA, Ca D, Rees PN, Chen GM, Walker CG, French S, Brown ED, Bérdy J, Liu DY, Magarvey NA. Assembly and clustering of natural antibiotics guides target identification. Nat Chem Biol. 2016;12(4):233–9.PubMedGoogle Scholar
  87. 87.
    Gillespie DE, Brady SF, Bettermann AD, Cianciotto NP, Liles MR, Rondon MR, Clardy J, Goodman RM, Handelsman J. Isolation of antibiotics turbomycin A and B from a metagenomic library of soil microbial DNA. Appl Environ Microbiol. 2002;68(9):4301–6.PubMedPubMedCentralGoogle Scholar
  88. 88.
    Tanaka Y, Tokuyama S, Ochi K. Activation of secondary metabolite-biosynthetic gene clusters by generating rsmG mutations in Streptomyces griseus. J Antibiot (Tokyo). 2009;62(12):669–73.Google Scholar
  89. 89.
    Tanaka Y, Kasahara K, Hirose Y, Murakami K, Kugimiya R, Ochi K. Activation and products of the cryptic secondary metabolite biosynthetic gene clusters by rifampin resistance (rpoB) mutations in actinomycetes. J Bacteriol. 2012;195(10):2959–70.Google Scholar
  90. 90.
    Yoon V, Nodwell JR. Activating secondary metabolism with stress and chemicals. J Ind Microbiol Biotechnol. 2014;41(2):415–24.PubMedGoogle Scholar
  91. 91.
    Onaka H. Novel antibiotic screening methods to awaken silent or cryptic secondary metabolic pathways in actinomycetes. J Antibiot (Tokyo). 2017;70(8):865–70.Google Scholar
  92. 92.
    Yamanaka K, Reynolds KA, Kersten RD, Tyan KS, Gonzalez DJ, Nizet V, Dorrestein PC, Moore BS. Direct cloning and refactoring of a silent lipopeptide biosynthetic gene cluster yields the antibiotic taromycin A. Proc Natl Acad Sci U S A. 2014;111(5):1957–62.PubMedPubMedCentralGoogle Scholar
  93. 93.
    Li Y, Li Z, Yamanaka K, Xy Y, Zhang W, Wlamakis H, Kolter R, Moore BS, Qian PY. Directed natural product biosynthesis gene cluster capture and expression in the model bacterium Bacilus subtilis. Sci Rep. 2015;5(9383). Google Scholar
  94. 94.
    Banik JJ, Brady SF. Cloning and characterization of new glycopeptide gene clusters found in environmental DNA megalibrary. Proc Natl Acad Sci U S A. 2008;105(45):17273–7.PubMedPubMedCentralGoogle Scholar
  95. 95.
    Cohen LJ, Han S, Huang YH, Brady SF. Identification of the colicin V bacteriocin gene cluster by functional screening of a human microbiome metagenomic library. ACS Infec Dis; 2017. 4(1):27–32.Google Scholar
  96. 96.
    Wright GD. Perspective: synthetic biology revives antibiotics. Nature. 2014;509(7498):S13.PubMedGoogle Scholar
  97. 97.
    Thaker MN, Wright GD. Opportunities for synthetic biology in antibiotics:expanding glycopeptide diversity. ACS Synth Biol. 2015;4(3):195–206.PubMedGoogle Scholar
  98. 98.
    Braff D, Shis D, Collins JJ. Synthetic biology platform technologies for antimicrobial applications. Adv Drug Deliv Rev. 2016;105(Pt A):35–43.PubMedGoogle Scholar
  99. 99.
    Yim G, Wang W, Thaker MN, Tan S, Wriight GD. How to make a glycopeptide: asynthetic biology approach to expand glycopeptide antibiotic chemcial diversity. ACS Infect. Dis. 2016;2(9):642–50.PubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Fern R. McSorley
    • 1
  • Jarrod W. Johnson
    • 1
  • Gerard D. Wright
    • 1
    Email author
  1. 1.Department of Biochemistry and Biomedical SciencesMcMaster University, Michael G. DeGroote Institute for Infectious Disease Research, McMaster UniversityHamiltonCanada

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