Bacterial Infectious Disease Threat

  • Patrick L. Iversen


Human disease resulting from bacterial infection is a lottery. Outbreaks can spread though like wildfire through the global human population. Global bacterial diseases including syphilis and tuberculosis have been the drivers of modern medicine from drug discovery to objective clinical trials. Bacteria can create modular genetic segments in plasmids and exploit bacteriophage in transfer of genome segments among bacteria to enable resilience. Bacteria are also able to transfer genetic material with eukaryotes including humans through a process of horizontal gene transfer. We live in an age of effective antibacterial drugs in an effort to control infection and improve survival. Recent appreciation of bacteria living in our bodies, the microbiome, illuminates complex metabolome interactions with the human host. The microbiome and the accompanying metabolites can manipulate human resilience.


Microbiome Syphilis Tuberculosis Horizontal gene transfer Human chorionic gonadotropin Antibiotics 


  1. Acevedo HF, Koide SS, Slifkin M, Mauro T, Campbell-Acevedo EA. Choriogonadotropin-like antigen in a strain of Streptococcus faecalis and a strain of Staphylococcus simulans: detection, identification, and characterization. Infect Immun. 1981;31:487–94.PubMedPubMedCentralGoogle Scholar
  2. Acevedo HF, Raikow RB, Powell JF, Stevens VC. Effects of immunization against human chorionic gonadotropin on the growth and spread of Lewis lung carcinoma and spontaneous mammary adenocarcinoma in mice. Canc Detect Prev Suppl. 1987;1:477–86.Google Scholar
  3. Alexander FE. Is mycoplasma pneumonia associated with childhood acute lymphoblastic leukemia? Cancer Causes Control. 1997;8(5):803–11.CrossRefGoogle Scholar
  4. Anderson LA, et al. Relationship between Helicobacter pylori infection and gastric atrophy and the stages of oesophageal inflammation, metaplasia, adenocarcinoma sequence: results from the FINBAR case-control study. Gut. 2008;57:734–9.CrossRefGoogle Scholar
  5. Backus BT, Affronti LF. Tumor-associated bacteria capable of producing a human choriogonadotropin-like substance. Infect Immun. 1981;32:1211–5.PubMedPubMedCentralGoogle Scholar
  6. Blaser MJ. Missing microbes. How the overuse of antibiotics is fueling our modern plagues. New York: Henry Holt and Company; 2014.Google Scholar
  7. Bordenstein SR, Theis KR. Host biology in light of the microbiome: ten principles of holobionts and hologenomes. PLoS Biol. 2015;13(8):e1002226.CrossRefGoogle Scholar
  8. Broder LE, Weintraub BD, Rosen SW, Cohen MH, Tejada F. Placental proteins and their subunits as tumor markers in prostatic carcinoma. Cancer. 1977;40:211–6.CrossRefGoogle Scholar
  9. Buffie CG, Bucci V, Stein RR, McKenney PT, Ling L, Gobourne A, No D, Liu H, Kinnebrew M, Viale A, Littman E, van den Brink MRM, Jenq RR, Taur Y, Sander C, Cross J, Toussaint NC, Xavier JB, Pamer EG. Precision microbiome restoration on bile acid-mediated resistance to Clostridium difficile. Nature. 2015;517(7533):205–8.CrossRefGoogle Scholar
  10. Burnett J. The Navajo Nation’s own trail of tears’. National Public Radio, All Things Considered. 2005, June 14.Google Scholar
  11. Chang CM, Landgren O, Koshiol J, Bjorkholm M, Love TJ, Kristinsson SY. Borrelia and subsequent risk of solid tumors and hematologic malignancies in Sweden. Int J Cancer. 2012;131(9):2208–9.CrossRefGoogle Scholar
  12. Chen Y, Blaser MJ. Inverse associations of Helicobacter pylori asthma and allergies. Arch Intern Med. 2007;167:821–7.CrossRefGoogle Scholar
  13. Chen Y, Blaser MJ. Helicobacter pylori colonization is inversely associated with childhood asthma. J Infect Dis. 2008;198:553–60.CrossRefGoogle Scholar
  14. Chen ZQ, Zhang GC, Gong XD, Lin C, Gao X, Liang GJ, Yue XL, Chen XS, Cohen MS. Syphilis in China: results of a national surveillance programme. Lancet. 2007;369:132–8.CrossRefGoogle Scholar
  15. Clemente JC, Pehrsson EC, Blaser MJ, Sandhu K, Gao Z, Wang B, Magris M, Hidalgo G, Contreras M, Noya-Alarcon O, Lander O, McDonald J, Cox M, Walter J, Oh PL, Ruiz JF, Rodriguez S, Shen N, Song SJ, Metcalf J, Knight R, Dantas G, Dominguez-Bello MG. The microbiome of uncontacted Amerindians. Sci Adv. 2015;1:e1500183.CrossRefGoogle Scholar
  16. Cohen H, Strampp A. Bacterial synthesis of a substance similar to human chorionic gonadotropin. Proc Soc Exp Biol Med. 1976;152:408–10.CrossRefGoogle Scholar
  17. Cox L, et al. Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences. Cell. 2014;158:705–21.CrossRefGoogle Scholar
  18. CTV News. First NDM-1 superbug case confirmed in Ontario. 2010, August 28.Google Scholar
  19. Czerwiec PS, Melner MH, Puett D. Transiently elevated levels of c-foc and c-myc oncogene messenger ribonucleic acids in cultured murine Leydig tumor cells after addition of human chorionic gonadotropin. Mol Endocrinol. 1989;3:105–9.CrossRefGoogle Scholar
  20. Da Silva GJ, Doningues S. Insights on the horizontal gene transfer of carbapenemase determinants in the opportunistic pathogen Acinetobacter baumannii. Microorganisms. 2016;4:29–52.CrossRefGoogle Scholar
  21. Daniel TM. Tuberculosis in history: did it change the way we live? In: Schlossberg D, editor. Tuberculosis and nontuberculosis mycobacterial infections. 6th ed. Washington, DC: ASM Press; 2011. p. 3–10.Google Scholar
  22. Denschle K. Tubercuosis amoung the navajo. Am Rev Respir Dis. 1959;80:200–6.Google Scholar
  23. Devi GR, Oldenkamp JR, London CA, Iversen PL. Inhibition of human chorionic gonadotropin β-subunit modulates the mitogenic effect of c-myc in human prostate cancer cells. Prostate. 2002;53:200–10.CrossRefGoogle Scholar
  24. Domingue GJ, Acevedo HF, JE P, Stevens VC. Antibodies to bacterial vaccines demonstrating specificity for human choriogonadotropin (hCG) and immunochemical detection of hCG-like factor in subcellular bacterial fractions. Infect Immun. 1986;53:95–8.PubMedPubMedCentralGoogle Scholar
  25. Forman D. Association between infection with Helicobacter pylori and the risk of gastric cancer: evidence from a prospective investigation. Br Med J. 1991;302:1302–5.CrossRefGoogle Scholar
  26. Freeman VJ. Studies on the virulence of bacteriophage-infected strains of Corynebacterium diphtheriae. J Bacteriol. 1951;61(6):675–688.Google Scholar
  27. Frobisher M, Parsons EI, Updyke E. The correlation of laboratory and clinical evidence of virulence of C. diphtheriae. Am J Public Health. 1947;40:704–9.Google Scholar
  28. Geller BL, Deere JD, Stein DA, Kroeker AD, Moulton HM, Iversen PL. Inhibition of gene expression in Escherichia coli by antisense Phosphorodiamidate Morphiolino oligomers. Antimicrob Agents Chemother. 2003;47(10):3233–9.CrossRefGoogle Scholar
  29. Geller BL, Deere JD, Iversen PL. Antisense antibacterial method and compound. United States Patent Application US2013/0289091. 2004.Google Scholar
  30. Geller BL, Deere TL, Iversen PL. Antisense phosphorodiamidate morpholino oligomer inhibits variability of Escherichia coli in pure cultures and in mouse peritonitis. J Antimicrob Chemother. 2005;10:1093.Google Scholar
  31. Geller BL, Iversen PL, Tilley L. Antisense antibacterial method and compound. United States Patent US 7,790,694. 2010.Google Scholar
  32. Goodman LS, Gilman A. The pharmacological basis of therapeutics. 2nd ed. New York: Macmillan Company; 1955. p. 1234.Google Scholar
  33. Hayden D. Pox. New York: Basic Books; 2003.Google Scholar
  34. Hicks L, et al. US outpatient antibiotic prescribing, 2010. N Engl J Med. 2013;368:1461–2.CrossRefGoogle Scholar
  35. Hook EW III, Stephens J, Peeling RW. Syphilis control- a continuing challenge. N Engl J Med. 2004;351:122–4.CrossRefGoogle Scholar
  36. Hotopp JCD. Horizontal gene transfer between bacteria and animals. Trends Genet. 2011;27(4):157–63.CrossRefGoogle Scholar
  37. Iversen PL. Antisense antibacterial compounds and methods. United States Patent Application US2012/0122769. 2012.Google Scholar
  38. Iversen PL, Iwen P, Weller DL, Matthews P, Weller DD, Brand RE. Evaluation of ion-trapping engines for delivery of novel therapeutics into Helicobacter felis. In: IBC conference, Helicobacter Pylori and gastrointestinal disorders. Washington, DC; 1997a, January 27–28.Google Scholar
  39. Iversen PL, Iwen P, Weller DL, Matthews P, Weller DD, Brand RE. Ion trapping engines for delivery of chloramphenicol for treatment of Helicobacter pylori. Washington, DC: American Gastroenterological Association; 1997b.Google Scholar
  40. Iversen PL, Iwen P, Weller DL, Brand RE. Ion Trapping Engines for Delivery of Novel Therapeutics for Treatment of Helicobacter pylori. Washington, DC: American Gastroenterological Association; 1997c, June.Google Scholar
  41. Iversen P, Mourich D, Moulton H. Monoclonal antibodies to two epitopes of β-human chorionic gonadotropin tor the treatment of cancer. Curr Opin Mol Ther. 2003;5(2):156–60.PubMedGoogle Scholar
  42. Kellen JA, Kolin A, Mirakian A, Acevedo HF. Effects of antibodies to choriogonadotropin in malignant growth. II Solid transplantable tumors. Cancer Immunol Immunother. 1982;13:2–4.CrossRefGoogle Scholar
  43. Koshiol J, Wozniak A, Cook P, Adaniel C, Acevedo J, Azocar L, Hsing W, Pasetti MF, Miguel JF, Ferreccio C. Salmonella enerica serovar Typhi and callbladder cancer: a case-controlled study and meta-analysis. Cancer Med. 2016;5(11):3310–25.CrossRefGoogle Scholar
  44. Kozyrskyj AL, et al. Increased risk of childhood asthma from antibiotic use early in life. Chest. 2007;131:1753–9.CrossRefGoogle Scholar
  45. Lacroix B, Citovsky V. Transfer of DNA from Bacteria to eukaryotes. MBio. 2016;7(4):e00863-16.CrossRefGoogle Scholar
  46. Lander ES, et al. Initial sequencing and analysis of the human genome. Nature. 2001;409:860–921.CrossRefGoogle Scholar
  47. Livingston VWC, Livingston AM. Some cultural, immunological, and biochemical properties of progenitor cryptocides. Trans NY Acad Sci. 1974;36:569–82.CrossRefGoogle Scholar
  48. Maruo T, Cohen H, Segal SJ, Koide SS. Production of choriogonadotropin-like factor by a microorganism. Proc Natl Acad Sci U S A. 1979;76:6622–6.CrossRefGoogle Scholar
  49. Mindell DP. Phylogenetic consequences of symbiosis: Eukarya and Eubacteria are not monophyletic taxa. Biosystems. 1992;27(1):53–62.CrossRefGoogle Scholar
  50. MMWR. Detection of Enterobacteriaceae isolates carrying metallo-beta-lactamase – United States, 2010. MMWR Morb Mortal Wkly Rep. 2010;59(24):750.Google Scholar
  51. Monari P, Farisoglio C, Calzavara Pinton PG. Borrelia burgdorfei-associated primary cutaneous marginal zone B-cell lymphoma: a case report. Dermatology. 2007;215(3):229–32.CrossRefGoogle Scholar
  52. Mourich D, Marshall N, Iversen P. Tumor expressed Beta-hCG promotes IgG 2a responses which are less efficient for CTL cross-priming. In: 12th international congress of immunology and 4th annual conference of FOCIS. Immunology. 2004: 155–159.Google Scholar
  53. Muhammad R, Bollampalli VP, Chryssanthou E, Maeurer MJ, Iversen PL, Rothfuchs AG. Peptide phosphorodiamidate morpholino oliogmers as antisense therapeutics for Mycobacterium tuberculosis. ECCMID 2012. 2012.Google Scholar
  54. Muir A, Weinbren MJ. New Delhi metallo-beta-lactamase: a cautionary tale. J Hosp Infect. 2010;75(3):239–40.CrossRefGoogle Scholar
  55. Nomura A, et al. Helicobacter pylori infection and gastric carcinoma among Japanese Americans in Hawaii. N Engl J Med. 1991;325:1132–6.CrossRefGoogle Scholar
  56. Parsonnet J, et al. Helicobacter pylori infection and the risk of gastric carcinoma. N Engl J Med. 1991;325:1127–31.CrossRefGoogle Scholar
  57. Qvist G. John Hunter’s alleged syphilis. Ann R Coll Surg Engl. 1977;59:205–9.PubMedCentralGoogle Scholar
  58. Rad R, et al. CD25+/Foxp3+ T cells regulate gastric inflammation and Helicobacter pylori colonization in vivo. Gastroenterology. 2006;131:525–37.CrossRefGoogle Scholar
  59. Reibman J, et al. Asthma is inversely associated with Helicobacter pylori status in an urban population. PLoS One. 2008;3(e4060):1–6.Google Scholar
  60. Robinson K, et al. Helicobacter pylori-induced peptic ulcer disease is associated with inadequate regulatory T cell responses. Gut. 2008;57:1375–85.CrossRefGoogle Scholar
  61. Salzberg SL, et al. Microbial genes in the human genome: lateral transfer of gene loss? Science. 2001;292:1903–6.CrossRefGoogle Scholar
  62. Science Daily. Superbugs’ found breeding in sewage plants. 2013, December 16.Google Scholar
  63. Stamm LV, Bergen HL. A point mutation associated with bacterial macrolide resistance in both 23S rRNA genes of an erythromycin-resistant Treponema pallidum clinical isolate. Antimicrob Agents Chemother. 2000;44:806–7.CrossRefGoogle Scholar
  64. Talley NJ, et al. Gastric adenocarcinoma and Helicobacter pylori infection. J Natl Cancer Inst. 1991;83:1734–9.CrossRefGoogle Scholar
  65. Tillett WS, et al. The treatment of lobular pneumonia with penicillin. J Clin Invest. 1945;4:589–94.CrossRefGoogle Scholar
  66. Tilley LD, Mellbye BL, Puckett SE, Iversen PL, Geller BL. Antisense peptide-phosphoerodiamidate morpholino oligomer conjugate: dose-response in mice infected with Escherichia coli. J Antimicrob Chemother. 2007;59:66–73.CrossRefGoogle Scholar
  67. Trasande L, et al. Infant antibiotic exposures and early-life body mass. Intl J Obes. 2013;37:16–23.CrossRefGoogle Scholar
  68. Vaezi MF, et al. CagA-positive strains of Helicobacter pylori may protect against Barrett’s esophagus. Am J Gastroenerol. 2000;95:2206–11.CrossRefGoogle Scholar
  69. Van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013;368:407–15.CrossRefGoogle Scholar
  70. Vicari JJ, et al. The seroprrevalence of cagA-positive Helicobacter pylori strains in the spectrum of gastroesophageal reflux disease. Gastroenterology. 1998;115:50–7. Scholar
  71. Yong D, Toleman MA, Giske CG, Cho HS, Sundman K, Lee K, Walsh TR. Characterization of anew metallo-beta-lactamase gene bla(NDM-1), and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumonia sequence type 14 from India. Antimicrob Agents Chemother. 2009;53(12):5046–54.CrossRefGoogle Scholar

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© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Patrick L. Iversen
    • 1
  1. 1.LS PharmaOregon State UniversityGrand JctUSA

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