Bioengineered probiotics represent the next generation of whole cell–mediated biotherapeutics. Advances in synthetic biology, genome engineering, and DNA sequencing and synthesis have enabled scientists to design and develop probiotics with increased stress tolerance and the ability to target specific pathogens and their associated toxins, as well as to mediate targeted delivery of vaccines, drugs, and immunomodulators directly to host cells. Herein, we review the most significant advances in the development of this field. We discuss the critical issue of biological containment and consider the role of synthetic biology in the design and construction of the probiotics of the future.


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Literature Cited

  1. Aakko J, Sánchez B, Gueimonde M, Salminen S. 2014. Assessment of stress tolerance acquisition in the heat-tolerant derivative strains of Bifidobacteriumanimalis subsp. lactis BB-12 and Lactobacillus rhamnosus GG. J. Appl. Microbiol 117:239–48 [Google Scholar]
  2. Adel-Patient K, Ah-Leung S, Creminon C, Nouaille S, Chatel J. et al. 2005. Oral administration of recombinant Lactococcus lactis expressing bovine β-lactoglobulin partially prevents mice from sensitization. Clin. Exp. Allergy 35:539–46 [Google Scholar]
  3. Alivisatos AP, Blaser MJ, Brodie EL, Chun M, Dangl JL. et al. 2015. A unified initiative to harness Earth's microbiomes. Science 350:507–8 [Google Scholar]
  4. Amalaradjou M, Bhunia A. 2013. Bioengineered probiotics, a strategic approach to control enteric infections. Bioengineered 4:379–87 [Google Scholar]
  5. Asadullah K, Sterry W, Volk H. 2003. Interleukin-10 therapy: review of a new approach. Pharmacol. Rev. 55:241–69 [Google Scholar]
  6. Barzegari A, Saei AA. 2012. Designing probiotics with respect to the native microbiome. Future Microbiol 7:571–75 [Google Scholar]
  7. Besselink MG, Van Santvoort HC, Buskens E, Boermeester MA, Van Goor H. et al. 2008. Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial. Lancet 371:651–59 [Google Scholar]
  8. Braat H, Rottiers P, Hommes D, Huyghebaert N, Remaut E. et al. 2006. A phase I trial with transgenic bacteria expressing interleukin-10 in Crohn's disease. Clin. Gastroenterol. Hepatol. 4:754–59 [Google Scholar]
  9. Bravo JA, Forsythe P, Chew MV, Escaravage E, Savignac HM. et al. 2011. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. PNAS 108:16050–55 [Google Scholar]
  10. Broadbent JR, Larsen RL, Deibel V, Steele JL. 2010. Physiological and transcriptional response of Lactobacillus casei ATCC 334 to acid stress. J. Bacteriol. 192:2445–58 [Google Scholar]
  11. Butel M. 2014. Probiotics, gut microbiota and health. Méd. Mal. Infect. 44:1–8 [Google Scholar]
  12. Carmen SD, de Moreno de LeBlanc A, Martin R, Chain F, Langella P. 2014. Genetically engineered immunomodulatory Streptococcus thermophilus strains producing antioxidant enzymes exhibit enhanced anti-inflammatory activities. Appl. Environ. Microbiol. 80:869–77 [Google Scholar]
  13. Chan CT, Lee JW, Cameron DE, Bashor CJ, Collins JJ. 2016. “Deadman” and “Passcode” microbial kill switches for bacterial containment. Nat. Chem. Biol. 12:82–86 [Google Scholar]
  14. Chang TL-Y, Chang C-H, Simpson DA, Xu Q, Martin PK. et al. 2003. Inhibition of HIV infectivity by a natural human isolate of Lactobacillus jensenii engineered to express functional two-domain CD4. PNAS 100:11672–77 [Google Scholar]
  15. Chen H, Lai Y, Chen C, Chu T, Lin W. et al. 2010. Probiotic Lactobacillus casei expressing human lactoferrin elevates antibacterial activity in the gastrointestinal tract. Biometals 23:543–54 [Google Scholar]
  16. Collins SM, Surette M, Bercik P. 2012. The interplay between the intestinal microbiota and the brain. Nat. Rev. Microbiol. 10:735–42 [Google Scholar]
  17. Considine KM, Kelly AL, Fitzgerald GF, Hill C, Sleator RD. 2008. High-pressure processing–effects on microbial food safety and food quality. FEMS Microbiol. Lett. 281:1–9 [Google Scholar]
  18. Corr SC, Li Y, Riedel CU, O'Toole PW, Hill C, Gahan CG. 2007. Bacteriocin production as a mechanism for the antiinfective activity of Lactobacillus salivarius UCC118. PNAS 104:7617–21 [Google Scholar]
  19. Cortes-Perez N, Azevedo V, Alcocer-González J, Rodriguez-Padilla C, Tamez-Guerra R. et al. 2005. Cell-surface display of E7 antigen from human papillomavirus type-16 in Lactococcus lactis and in Lactobacillus plantarum using a new cell-wall anchor from lactobacilli. J. Drug Target 13:89–98 [Google Scholar]
  20. Cronin M, Morrissey D, Rajendran S, Mashad SME, Sinderen DV. et al. 2010. Orally administered bifidobacteria as vehicles for delivery of agents to systemic tumors. Mol. Ther. 18:1397–407 [Google Scholar]
  21. Cronin M, Sleator RD, Hill C, Fitzgerald GF, Van Sinderen D. 2008. Development of a luciferase-based reporter system to monitor Bifidobacterium breve UCC2003 persistence in mice. BMC Microbiol 8:161 [Google Scholar]
  22. Culligan EP, Hill C, Sleator RD. 2009. Probiotics and gastrointestinal disease: successes, problems and future prospects. Gut Pathog 1:19 [Google Scholar]
  23. Culligan EP, Sleator RD, Marchesi JR, Hill C. 2014. Metagenomics and novel gene discovery: promise and potential for novel therapeutics. Virulence 5:399–412 [Google Scholar]
  24. Cummings JH, Macfarlane GT. 1997. Role of intestinal bacteria in nutrient metabolism. Clin. Nutr. 16:3–11 [Google Scholar]
  25. Daniel C, Repa A, Wild C, Pollak A, Pot B. et al. 2006. Modulation of allergic immune responses by mucosal application of recombinant lactic acid bacteria producing the major birch pollen allergen Bet v 1. Allergy 61:812–19 [Google Scholar]
  26. Daniel C, Sebbane F, Poiret S, Goudercourt D, Dewulfa J. et al. 2009. Protection against Yersinia pseudotuberculosis infection conferred by a Lactococcus lactis mucosal delivery vector secreting LcrV. Vaccine 27:1141–44 [Google Scholar]
  27. Danino T, Prindle A, Kwong GA, Skalak M, Li H. et al. 2015. Programmable probiotics for detection of cancer in urine. Sci. Transl. Med. 7:289ra84 [Google Scholar]
  28. de Moreno de LeBlanc A, LeBlanc JG, Perdigón G, Miyoshi A, Langella P. et al. 2008. Oral administration of a catalase-producing Lactococcus lactis can prevent a chemically induced colon cancer in mice. J. Med. Microbiol. 57100–5 [Google Scholar]
  29. Desbonnet L, Garrett L, Clarke G, Bienenstock J, Dinan TG. 2008. The probiotic Bifidobacteria infantis: an assessment of potential antidepressant properties in the rat. J. Psychiatric Res. 43:164–74 [Google Scholar]
  30. Desmond C, Fitzgerald GF, Stanton C, Ross RP. 2004. Improved stress tolerance of GroESL-overproducing Lactococcus lactis and probiotic Lactobacillus paracasei NFBC 338. Appl. Environ. Microbiol 70:5929–36 [Google Scholar]
  31. Desmond C, Stanton C, Fitzgerald GF, Collins K, Ross RP. 2001. Environmental adaptation of probiotic lactobacilli towards improvement of performance during spray drying. Int. Dairy J. 11:801–8 [Google Scholar]
  32. Dewall M, Cheng D. 2011. The minimal genome: a metabolic and environmental comparison. Brief. Funct. Genom. 10:312–15 [Google Scholar]
  33. Dinan T, Cryan J. 2015. The impact of gut microbiota on brain and behaviour: implications for psychiatry. Curr. Opin. Clin. Nutr. Metab. Care 18:552–58 [Google Scholar]
  34. Dinan TG, Cryan JF. 2016. Mood by microbe: towards clinical translation. Genome Med 8:36 [Google Scholar]
  35. Dinan TG, Stanton C, Cryan JF. 2013. Psychobiotics: a novel class of psychotropic. Biol. Psychiatry 74:720–26 [Google Scholar]
  36. Duc LH, Hong HA, Fairweather N, Ricca E, Cutting SM. 2003. Bacterial spores as vaccine vehicles. Infect. Immun. 71:2810–18 [Google Scholar]
  37. FAO/WHO. 2001. Expert consultation on evaluation of health and nutritional properties of probiotics in food including milk powder with live lactic acid bacteria. Cordoba, Argent: FAO/WHO
  38. Field D, Quigley L, O'Connor PM, Rea MC, Daly K. et al. 2010. Studies with bioengineered Nisin peptides highlight the broad-spectrum potency of Nisin V. Microb. Biotechnol. 3:473–86 [Google Scholar]
  39. Focareta A, Paton JC, Morona R, Cook J, Paton AW. 2006. A recombinant probiotic for treatment and prevention of cholera. Gastroenterology 130:1668–95 [Google Scholar]
  40. Forssten SD, Sindelar CW, Ouwehand AC. 2011. Probiotics from an industrial perspective. Anaerobe 17:410–13 [Google Scholar]
  41. Gallagher RR, Patel JR, Interiano AL, Rovner AJ, Isaacs FJ. 2015. Multilayered genetic safeguards limit growth of microorganisms to defined environments. Nucleic Acids Res 43:1945–54 [Google Scholar]
  42. García JL, Díaz E. 2014. Plasmids as tools for containment. Microbiol. Spectr. 2: PLAS-0011-2013 [Google Scholar]
  43. Gibson DG, Glass JI, Lartigue C, Noskov VN, Chuang RY. et al. 2010. Creation of a bacterial cell controlled by a chemically synthesized genome. Science 329:52–56 [Google Scholar]
  44. Gueimonde M, Sánchez B. 2012. Enhancing probiotic stability in industrial processes. Microbial. Ecol. Health Dis. 23:18562 [Google Scholar]
  45. Guimarãesa VD, Gabriel JE, Lefèvre F, Cabanes D, Gruss A. et al. 2005. Internalin-expressing Lactococcus lactis is able to invade small intestine of guinea pigs and deliver DNA into mammalian epithelial cells. Microbes Infect 7:836–44 [Google Scholar]
  46. Hamady Z. 2013. Novel xylan-controlled delivery of therapeutic proteins to inflamed colon by the human anaerobic commensal bacterium. Ann. R. Coll. Surg. Engl. 95:235–40 [Google Scholar]
  47. Hanson ML, Hixon JA, Li W, Felber BK, Anver M. et al. 2014. Oral delivery of IL27 recombinant bacteria attenuates immune colitis in mice. Gastroenterology 146:210–21 [Google Scholar]
  48. Harris A. 2002. Hypoxia: a key regulatory factor in tumour growth. Nat. Rev. Cancer 2:38–47 [Google Scholar]
  49. Hernani ML, Ferreira P, Ferreira D, Miyaji E, Ho P, Oliveira M. 2011. Nasal immunization of mice with Lactobacillus casei expressing the pneumococcal surface protein C primes the immune system and decreases pneumococcal nasopharyngeal colonization in mice. FEMS Immunol. Med. Microbiol 62263–72 [Google Scholar]
  50. Hoban AE, Stilling RM, Ryan FJ, Shanahan F, Dinan TG. et al. 2016. Regulation of prefrontal cortex myelination by the microbiota. Transl. Psychiatry 6:e724 [Google Scholar]
  51. Huibregtse I, Snoeck V, Creus AD, Braat H, Jong ED. et al. 2007. Induction of ovalbumin-specific tolerance by oral administration of Lactococcus lactis secreting ovalbumin. Gastroenterology 133:517–28 [Google Scholar]
  52. Hutchison CA 3rd, Chuang RY, Noskov VN, Assad-Garcia N, Deerinck TJ. et al. 2016. Design and synthesis of a minimal bacterial genome. Science 351:aad6253 [Google Scholar]
  53. Hwang IY, Tan MH, Koh E, Ho CL, Poh CL, Chang MW. 2014. Reprogramming microbes to be pathogen-seeking killers. ACS Synth. Biol. 3:228–37 [Google Scholar]
  54. Innocentin S, Guimarães V, Miyoshi A, Azevedo V, Langella P. et al. 2009. Lactococcus lactis expressing either Staphylococcus aureus fibronectin-binding protein A or Listeria monocytogenes internalin A can efficiently internalize and deliver DNA in human epithelial cells. Appl. Environ. Microbiol 75:4870–78 [Google Scholar]
  55. Jenkins TA, Nguyen JCD, Polglaze KE, Bertrand PP. 2016. Influence of tryptophan and serotonin on mood and cognition with a possible role of the gut-brain axis. Nutrients 8:pii:E56 [Google Scholar]
  56. Jiang Y, Ren F, Liu S, Zhao L, Guo H, Hou C. 2015. Enhanced acid tolerance in Bifidobacterium longum by adaptive evolution: comparison of the genes between the acid-resistant variant and wild-type strain. J. Microbiol. Biotechnol. 26:452–60 [Google Scholar]
  57. Jiménez JJ, Diep DB, Borrero J, Gútiez L, Arbulu S. et al. 2015. Cloning strategies for heterologous expression of the bacteriocin enterocin A by Lactobacillus sakei Lb790, Lb. plantarum NC8 and Lb. casei CECT475. Microb. Cell Fact 14:166 [Google Scholar]
  58. Johnston C, Coffey A, O'Mahony J, Sleator RD. 2010. Development of a novel oral vaccine against Mycobacterium avium paratuberculosis and Johne disease: a patho-biotechnological approach. Bioeng. Bugs 1:155–63 [Google Scholar]
  59. Johnston C, Douarre PE, Soulimane T, Pletzer D, Weingart H. et al. 2013. Codon optimisation to improve expression of a Mycobacterium avium ssp. paratuberculosis–specific membrane-associated antigen by Lactobacillus salivarius. Pathog. Dis 68:27–38 [Google Scholar]
  60. Johnston CD, Bannantine JP, Govender R, Endersen L, Pletzer D. et al. 2014. Enhanced expression of codon optimized Mycobacterium avium subsp. paratuberculosis antigens in Lactobacillus salivarius. Front. Cell. Infect. Microbiol 4:120 [Google Scholar]
  61. Kajikawa A, Zhang L, Long J, Nordone S, Stoeker L. et al. 2012. Construction and immunological evaluation of dual cell surface display of HIV-1 gag and Salmonella enterica serovar Typhimurium FliC in Lactobacillus acidophilus for vaccine delivery. Clin. Vaccine Immunol 19:1374–81 [Google Scholar]
  62. Kaushal G, Shao J. 2006. Oral delivery of B-lactamase by Lactococcus lactis subsp. lactis transformed with plasmid ss80. Int. J. Pharm 312:90–95 [Google Scholar]
  63. Kaushal G, Shao J. 2009. Genetically engineered normal flora for oral polypeptide delivery: dose-absorption response. J. Pharm. Sci. 98:2573–80 [Google Scholar]
  64. Komatsuzaki N, Nakamura T, Kimura T, Shima J. 2008. Characterization of glutamate decarboxylase from a high γ-aminobutyric acid (GABA)-producer, Lactobacillus paracasei. Biosci. Biotechnol. Biochem. 72:278–85 [Google Scholar]
  65. Kong W, Wanda SY, Zhang X, Bollen W, Tinge SA. et al. 2008. Regulated programmed lysis of recombinant Salmonella in host tissues to release protective antigens and confer biological containment. PNAS 105:9361–66 [Google Scholar]
  66. Koo OK, Amalaradiou MA, Bhunia AK. 2012. Recombinant probiotic expressing Listeria adhesion protein attenuates Listeria monocytogenes virulence in vitro. PLOS ONE 7:e29277 [Google Scholar]
  67. Kotula JW, Kerns SJ, Shaket LA, Siraj L, Collins JJ. et al. 2014. Programmable bacteria detect and record an environmental signal in the mammalian gut. PNAS 111:4838–43 [Google Scholar]
  68. Lee P. 2010. Biocontainment strategies for live lactic acid bacteria vaccine vectors. Bioengineered 1:75–77 [Google Scholar]
  69. Lee S, Belitsky BR, Brinker JP, Kerstein KO, Brown DW. et al. 2010. Development of a Bacillus subtilis–based rotavirus vaccine. Clin. Vaccine Immunol. 17:1647–55 [Google Scholar]
  70. Li H, Qiu T, Huang G, Cao Y. 2010a. Production of γ-aminobutyric acid by Lactobacillus brevis NCL912 using fed-batch fermentation. Microb. Cell Fact. 9:85 [Google Scholar]
  71. Li Q, Chen Q, Ruan H, Zhu D, He G. 2010b. Isolation and characterisation of an oxygen, acid and bile resistant Bifidobacterium animalis subsp. lactis Qq08. J. Sci. Food Agric 90:1340–46 [Google Scholar]
  72. Li Q, Wu Y-J. 2009. A fluorescent, genetically engineered microorganism that degrades organophosphates and commits suicide when required. Appl. Microbiol. Biotechnol 82749–56 [Google Scholar]
  73. Li X, Fu G, Fan Y, Liu W, Xj L. et al. 2003. Bifidobacterium adolescentis as a delivery system of endostatin for cancer gene therapy: selective inhibitor of angiogenesis and hypoxic tumor growth. Cancer Gene Ther 10:105–11 [Google Scholar]
  74. Limaye S, Haddad R, Cilli F, Sonis S, Colevas A. et al. 2013. Phase 1b, multicenter, single blinded, placebo-controlled, sequential dose escalation study to assess the safety and tolerability of topically applied AG013 in subjects with locally advanced head and neck cancer receiving induction chemotherapy. Cancer 119:4268–76 [Google Scholar]
  75. Lopez G, Anderson JC. 2015. Synthetic auxotrophs with ligand-dependent essential genes for a BL21(DE3) biosafety strain. ACS Synth. Biol. 4:1279–86 [Google Scholar]
  76. Lyte M. 2011. Probiotics function mechanistically as delivery vehicles for neuroactive compounds: microbial endocrinology in the design and use of probiotics. BioEssays 33:574–81 [Google Scholar]
  77. Mackay AD, Taylor MB, Kibbler CC, Hamilton-Miller JM. 1999. Lactobacillus endocarditis caused by a probiotic organism. Clin. Microbiol. Infect. 5:290–92 [Google Scholar]
  78. Mandell DJ, Lajoie MJ, Mee MT, Takeuchi R, Kuznetsov G. et al. 2015. Biocontainment of genetically modified organisms by synthetic protein design. Nature 518:55–60 [Google Scholar]
  79. Marinho F, Pacífico L, Miyoshi A, Azevedo V, Le Loir Y. et al. 2010. An intranasal administration of Lactococcus lactis strains expressing recombinant interleukin-10 modulates acute allergic airway inflammation in a murine model. Clin. Exp. Allergy 40:1541–51 [Google Scholar]
  80. Marlow GJ, Van Gent D, Ferguson LR. 2013. Why interleukin-10 supplementation does not work in Crohn's disease patients. World J. Gastroenterol. 19:3931–41 [Google Scholar]
  81. Martín MC, Pant N, Ladero V, Günaydın G, Andersen KK. et al. 2011. Integrative expression system for delivery of antibody fragments by lactobacilli. Appl. Environ. Microbiol. 77:2174–79 [Google Scholar]
  82. Martín R, Chain F, Miquel S, Natividad J, Sokol H. et al. 2014. Effects in the use of a genetically engineered strain of Lactococcus lactis delivering in situ IL-10 as a therapy to treat low-grade colon inflammation. Hum. Vaccines Immunother. 10:1611–21 [Google Scholar]
  83. Metchnikoff E. 1907. Lactic acid as inhibiting intestinal putrefaction. The Prolongation of Life: Optimistic Studies PC Mitchell 161–83 London: W. Heinemann [Google Scholar]
  84. Mimee M, Tucker AC, Voigt CA, Lu TK. 2015. Programming a human commensal bacterium, to sense and respond to stimuli in the murine gut microbiota. Cell Syst 1:62–71 [Google Scholar]
  85. Mohamadzadeh M, Duong T, Sandwick SJ, Hooverd T, Klaenhammer TR. 2009. Dendritic cell targeting of Bacillus anthracis protective antigen expressed by Lactobacillus acidophilus protects mice from lethal challenge. PNAS 106:4331–36 [Google Scholar]
  86. Mohamadzadeh M, Durmaz E, Zadeh M, Pakanati KC, Klaenhammer TR. 2010. Targeted expression of anthrax protective antigen by Lactobacillus gasseri as an anthrax vaccine. Future Microbiol 5:1289–96 [Google Scholar]
  87. Möhler H. 2012. The GABA system in anxiety and depression and its therapeutic potential. Neuropharmacology 62:42–53 [Google Scholar]
  88. Molina L, Ramos C, Ronchel M-C, Molin S, Ramos JL. 1998. Construction of an efficient biologically contained Pseudomonas putida strain and its survival in outdoor assays. Appl. Environ. Microbiol. 64:2072–87 [Google Scholar]
  89. Nielsen AA, Der BS, Shin J, Vaidyanathan P, Paralanov V. et al. 2016. Genetic circuit design automation. Science 352:aac7341 [Google Scholar]
  90. NIH. 2016. NIH guidelines for research involving recombinant or synthetic nucleic acid molecules. Bethesda, MD: NIH http://osp.od.nih.gov/sites/default/files/resources/NIH_Guidelines_PRN_1-sided.pdf
  91. O'Driscoll A, Sleator RD. 2013. Synthetic DNA: the next generation of big data storage. Bioengineered 4:123–25 [Google Scholar]
  92. O'Neill J. 2014. Antimicrobial resistance: tackling a crisis for the health and wealth of nations. Rev. Antimicrob. Resist. https://amr-review.org/sites/default/files/AMR%20Review%20Paper%20-%20Tackling%20a%20crisis%20for%20the%20health%20and%20wealth%20of%20nations_1.pdf
  93. Pacheco AR, Sperandio V. 2012. Shiga toxin in enterohemorrhagic E. coli: regulation and novel anti-virulence strategies. Front. Cell. Infect. Microbiol. 2:81 [Google Scholar]
  94. Paton A, Jennings M, Morona R, Wang H, Focareta A. et al. 2005. Recombinant probiotics for treatment and prevention of enterotoxigenic Escherichia coli diarrhea. Gastroenterology 128:1219–28 [Google Scholar]
  95. Paton A, Morona R, Paton J. 2000. A new biological agent for treatment of Shiga toxigenic Escherichia coli infections and dysentery in humans. Nat. Med. 6:265–70 [Google Scholar]
  96. Paton A, Morona R, Paton J. 2001. Neutralization of Shiga toxins Stx1, Stx2c, and Stx2e by recombinant bacteria expressing mimics of globotriose and globotetraose. Infect. Immun. 69:1967–70 [Google Scholar]
  97. Permpoonpattana P, Hong HA, Phetcharaburanin J, Huang E-M, Cook J. et al. 2011. Immunization with Bacillus spores expressing toxin A peptide repeats protects against infection with Clostridium difficile strains producing toxins A and B. Infect. Immun 79:2295–302 [Google Scholar]
  98. Petra AI, Panagiotidou S, Hatziagelaki E, Stewart JM, Conti P, Theoharides TC. 2015. Gut-microbiota–brain axis and its effect on neuropsychiatric disorders with suspected immune dysregulation. Clin. Ther. 37:984–95 [Google Scholar]
  99. Preston A, Mandrell R, Gibson B, Apicella M. 1996. The lipooligosaccharides of pathogenic Gram-negative bacteria. Crit. Rev. Microbiol. 22:139–80 [Google Scholar]
  100. Price RB, Shungu DC, Mao X, Nestadt P, Kelly C. et al. 2009. Amino acid neurotransmitters assessed by 1H MRS: relationship to treatment-resistance in major depressive disorder. Biol. Psychiatry 65:792–800 [Google Scholar]
  101. Rao S, Hu S, McHugh L, Lueders K, Henry K. et al. 2005. Toward a live microbial microbicide for HIV: commensal bacteria secreting an HIV fusion inhibitor peptide. PNAS 102:11993–98 [Google Scholar]
  102. Rautio M, Jousimies-Somer H, Kauma H, Pietarinen I, Saxelin M. et al. 1999. Liver abscess due to a Lactobacillus rhamnosus strain indistinguishable from L. rhamnosus strain GG. Clin. Infect. Dis 28:1159–60 [Google Scholar]
  103. Ritger K, Black S, Weaver K, Jones J, Gerber S. et al. 2011. Fatal laboratory-acquired infection with an attenuated Yersiniapestis strain—Chicago, Illinois, 2009. Morb. Mortal. Wkly. Rep. 60:201–30 [Google Scholar]
  104. Romijn AR, Rucklidge JJ. 2015. Systematic review of evidence to support the theory of psychobiotics. Nutr. Rev. 73:675–93 [Google Scholar]
  105. Rovner AJ, Haimovich AD, Katz SR, Li Z, Grome MW. et al. 2015. Recoded organisms engineered to depend on synthetic amino acids. Nature 518:89–93 [Google Scholar]
  106. Saeidi N, Wong C, Lo T, Nguyen H, Ling H. et al. 2011. Engineering microbes to sense and eradicate Pseudomonas aeruginosa, a human pathogen. Mol. Syst. Biol. 7:521 [Google Scholar]
  107. Salyers AA. 1984. Bacteroides of the human lower intestinal tract. Annu. Rev. Microbiol. 38:293–313 [Google Scholar]
  108. Sánchez B, López P, González-Rodríguez I, Suárez A, Margolles A, Urdaci M. 2011. A flagellin-producing Lactococcus strain: interactions with mucin and enteropathogens. FEMS Microbiol. Lett. 318:101–7 [Google Scholar]
  109. Sanders ME, Akkermans LMA, Haller D, Hammerman C, Heimbach J. et al. 2010. Safety assessment of probiotics for human use. Gut Microbes 1:164–85 [Google Scholar]
  110. Sasaki T, Fujimori M, Hamaji Y, Hama Y, Ito K. et al. 2006. Genetically engineered Bifidobacterium longum for tumor-targeting enzyme-prodrug therapy of autochthonous mammary tumors in rats. Cancer Sci 97:649–57 [Google Scholar]
  111. Sekirov I, Russell SL, Antunes LCM, Finlay BB. 2010. Gut microbiota in health and disease. Physiol. Rev. 90:859–904 [Google Scholar]
  112. Sheehan VM, Sleator RD, Fitzgerald GF, Hill C. 2006. Heterologous expression of BetL, a betaine uptake system, enhances the stress tolerance of Lactobacillus salivarius UCC118. Appl. Environ. Microbiol. 72:2170–77 [Google Scholar]
  113. Sheehan VM, Sleator RD, Hill C, Fitzgerald GF. 2007. Improving gastric transit, gastrointestinal persistence and therapeutic efficacy of the probiotic strain Bifidobacterium breve UCC2003. Microbiology 153:3563–71 [Google Scholar]
  114. Sibley L, Reljic R, Radford DS, Huang J-M, Hong HA. et al. 2014. Recombinant Bacillus subtilis spores expressing MPT64 evaluated as a vaccine against tuberculosis in the murine model. FEMS Microbiol. Lett. 358:170–79 [Google Scholar]
  115. Sleator RD. 2010a. The human superorganism: of microbes and men. Med. Hypotheses 74214–15 [Google Scholar]
  116. Sleator RD. 2010b. An overview of the current status of eukaryote gene prediction strategies. Gene 461:1–4 [Google Scholar]
  117. Sleator RD. 2010c. Probiotic therapy: recruiting old friends to fight new foes. Gut Pathog 2:5 [Google Scholar]
  118. Sleator RD. 2010d. Probiotics: a viable therapeutic alternative for enteric infections especially in the developing world. Discov. Med. 10:119–24 [Google Scholar]
  119. Sleator RD. 2011. Phylogenetics. Arch. Microbiol. 193:235–39 [Google Scholar]
  120. Sleator RD. 2012. Digital biology: a new era has begun. Bioengineered 3:311–12 [Google Scholar]
  121. Sleator RD. 2013a. A beginner's guide to phylogenetics. Microb. Ecol. 66:1–4 [Google Scholar]
  122. Sleator RD. 2013b. Synthetic ribosomes: making molecules that make molecules. Bioengineered 4:63–64 [Google Scholar]
  123. Sleator RD. 2014a. Genetics just got SEXY: sequences encoding XY. Bioengineered 5:214–15 [Google Scholar]
  124. Sleator RD. 2014b. The synthetic biology future. Bioengineered 5:69–72 [Google Scholar]
  125. Sleator RD. 2015a. Designer probiotics: development and applications in gastrointestinal health. World J. Gastrointest. Pathophysiol. 6:73–78 [Google Scholar]
  126. Sleator RD. 2015b. Under the microscope: from pathogens to probiotics and back. Bioengineered 6:275–82 [Google Scholar]
  127. Sleator RD. 2016. JCVI-syn3.0: a synthetic genome stripped bare!. Bioengineered 2:53–56 [Google Scholar]
  128. Sleator RD, Cronin M, Hill C. 2008a. Why appendectomies may lead to an increased risk of functional gastrointestinal disorders. Med. Hypotheses 71814–16 [Google Scholar]
  129. Sleator RD, Hill C. 2006. Patho-biotechnology: using bad bugs to do good things. Curr. Opin. Biotechnol. 17:211–16 [Google Scholar]
  130. Sleator RD, Hill C. 2007. Patho-biotechnology; using bad bugs to make good bugs better. Sci. Prog. 90:1–14 [Google Scholar]
  131. Sleator RD, Hill C. 2008a. “Bioengineered bugs” - a patho-biotechnology approach to probiotic research and applications. Med. Hypotheses 70167–69 [Google Scholar]
  132. Sleator RD, Hill C. 2008b. Designer probiotics: a potential therapeutic for Clostridium difficile. J. Med. Microbiol 57793–94 [Google Scholar]
  133. Sleator RD, Hill C. 2008c. Engineered pharmabiotics with improved therapeutic potential. Hum. Vaccin. 4:271–74 [Google Scholar]
  134. Sleator RD, Hill C. 2008d. New frontiers in probiotic research. Lett. Appl. Microbiol. 46:143–47 [Google Scholar]
  135. Sleator RD, Hill C. 2009. Rational design of improved pharmabiotics. J. Biomed. Biotechnol 2009:275287 [Google Scholar]
  136. Sleator RD, Shortall C, Hill C. 2008b. Metagenomics. Lett. Appl. Microbiol. 47:361–66 [Google Scholar]
  137. Smanski MJ, Zhou H, Claesen J, Shen B, Fischbach MA, Voigt CA. 2016. Synthetic biology to access and expand nature's chemical diversity. Nat. Rev. Microbiol. 14:135–49 [Google Scholar]
  138. Spinale JM, Ruebner RL, Copelovitch L, Kaplan BS. 2013. Long-term outcomes of Shiga toxin hemolytic uremic syndrome. Pediatr. Nephrol. 28:2097–105 [Google Scholar]
  139. Steidler L, Neirynck S, Huyghebaert N, Snoeck V, Vermeire A. et al. 2003. Biological containment of genetically modified Lactococcus lactis for intestinal delivery of human interleukin 10. Nat. Technol. 21:785–89 [Google Scholar]
  140. Termont S, Vandenbroucke K, Iserentant D, Neirynck S, Steidler L. et al. 2006. Intracellular accumulation of trehalose protects Lactococcus lactis from freeze-drying damage and bile toxicity and increases gastric acid resistance. Appl. Environ. Microbiol. 72:7694–700 [Google Scholar]
  141. Torre L, Bray F, Siegel R, Ferlay J, Lortet-Tieulent J, Jemal A. 2015. Global cancer statistics, 2012. Cancer J. Clin 65:87–108 [Google Scholar]
  142. Torres B, Jaenecke S, Timmis KN, Garcia JL, Diaz E. 2003. A dual lethal system to enhance containment of recombinant micro-organisms. Microbiology 149:3595–601 [Google Scholar]
  143. Vandenbroucke K, De Haard H, Beirnaert E, Dreier T, Lauwereys M. et al. 2010. Orally administered L.lactis secreting an anti-TNF nanobody demonstrate efficacy in chronic colitis. Mucosal Immunol 3:49–56 [Google Scholar]
  144. Vandenplas Y, Huys G, Daube G. 2015. Probiotics: an update. J. Pediatr. 91:6–21 [Google Scholar]
  145. Watson D, Sleator RD, Hill C, Gahan CG. 2008. Enhancing bile tolerance improves survival and persistence of Bifidobacterium and Lactococcus in the murine gastrointestinal tract. BMC Microbiol 8:176 [Google Scholar]
  146. Watve MG, Tickoo R, Jog MM, Bhole BD. 2001. How many antibiotics are produced by the genus Streptomyces. Arch. Microbiol. 176:386–90 [Google Scholar]
  147. Wells JM, Mercenier A. 2008. Mucosal delivery of therapeutic and prophylactic molecules using lactic acid bacteria. Nat. Rev. Microbiol. 6:349–62 [Google Scholar]
  148. Wu C, Chung T. 2007. Mice protected by oral immunization with Lactobacillus reuteri secreting fusion protein of Escherichia coli enterotoxin subunit protein. FEMS Immunol. Med. Microbiol 50:354–65 [Google Scholar]

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