Stress hormones (Adrenaline)

Shift towards Th2 (Th1 suppression)

Low cellular immune response

2 systems to sense immune imbalance

Quorum sensing Al-3/CAs system

Oxidative stress system

1- RBS replacement

2- RBS fusion

3- Biobrick Compatibility

4- Exclusion of HlyC

5- HlyB and HlyD independent

• So far, only a probiotic concept

• Biosafety of the researcher

Bacterial chassis modified by Berkeley UC 2007 to be non-immunogenic

• Population and environment safety

System evolved by Unicamp-Brazil 2009 that self-destructs when not in the appropriate media

Also Supported by:

• Bachen EA, Manuck SB, Cohen S, Muldoon MF, Raible R, Herbert TB, Rabin BS.Adrenergic blockade ameliorates cellular immune responses to mental stress in humans. Psychosom Med. 1995 Jul-Aug;57(4):366-72. Link to PubMed

• Barbara D. Tzschaschel, Carlos A. Guzmán,, Kenneth N. Timmis and Victor de Lorenzo. An Escherichia coli hemolysin transport system-based vector for the export of polypeptides: Export of shiga-like toxin IIeB subunit by Salmonella typhimurium aroA. Nature Biotechnology 14, 765 - 769 (1996) Article link

• Chrousos G.P., The hypothalamic–pituitary–adrenal axis and immune-mediated inflammation. New Engl. J. Med., 332 (1995), pp. 1351–1362. Link to PubMed

• Clarke MB, Hughes DT, Zhu C, Boedeker EC, Sperandio V (2006) The QseC sensor kinase: a bacterial adrenergic receptor. Proc Natl Acad Sci U S A 103: 10420–10425 Link to PubMed

• Clarke MB, Sperandio V (2005) Transcriptional regulation of flhDC by QseBC and sigma (FliA) in enterohaemorrhagic Escherichia coli. Mol Microbiol 57: 1734–1749. Link to PubMed

• Elenkov IJ, Chrousos GP. Stress Hormones, Th1/Th2 patterns, Pro/Anti-inflammatory Cytokines and Susceptibility to Disease. Trends Endocrinol Metab. 1999 Nov;10(9):359-368. Link to Pubmed

• Elenkov, I.J., Papanicolaou, D.A., Wilder, R.L. and Chrousos, G.P. (1996) Modulatory effects of glucocorticoids and catecholamines on human interleukin-12 and interleukin-10 production: clinical implications. Proc. Assoc. Amer. Physic. 108, 374–381. Link to Pubmed

• H. J. E. Beaumont, B. van Schooten, S. I. Lens, H. V. Westerhoff, and R. J. M. van Spanning. 2004. Nitrosomonas europaea expresses a Nitric Oxide Reductase during Nitrification. J. Bacteriol. 186: 4417–4421. Link to PubMed

• I.J. Elenkov, D.A. Papanicolaou, R.L. Wilder and G.P. Chrousos, Modulatory effects of glucocorticoids and catecholamines on human interleukin-12 and interleukin-10 production: clinical implications. Proc. Assoc. Amer. Physic., 108 (1996), pp. 374–381. [www.ncbi.nlm.nih.gov/pubmed/8902882 Link to PubMed]

• I.J. Elenkov, G. Hasko, K.J. Kovacs and E.S. Vizi, Modulation of lipopolysaccharide-induced tumor necrosis factor-alpha production by selective alpha- and beta-adrenergic drugs in mice. J. Neuroimmunol., 61 (1995b), pp. 123–131. Link to PubMed

• Ivaylo Gentschev, Guido Dietrich and Werner Goebel. The E. coli α-hemolysin secretion system and its use in vaccine development. Trends in Microbiology 10, 39-45 (2002)

• P Panina-Bordignon, et al. Beta2-agonists prevent Th1 development by selective inhibition of interleukin 12. J. Clin. Invest., 100 (1997), pp. 1513–1519. Link to PubMed

• P. Delepelaire. Type I secretion in Gram-negative bacteria. Biochimia et Biophysica Actca 1694, 149-161 (2004) Link to PubMed

• Reading NC, Rasko DA, Torres AG, Sperandio V. The two-component system QseEF and the membrane protein QseG link adrenergic and stress sensing to bacterial pathogenesis. Proc Natl Acad Sci U S A. 2009 Apr 7;106(14):5889-94. Epub 2009 Mar 16. Link to Pubmed

• Sperandio V, Torres AG, Jarvis B, Nataro JP, Kaper JB (2003) Bacteria-host communication: the language of hormones. Proc Natl Acad Sci USA 100: 8951–8956. Link to PubMed

• Sperandio V, Torres AG, Kaper JB (2002) Quorum sensing Escherichia coli regulators B and C (QseBC): a novel two-component regulatory system involved in the regulation of flagella and motility by quorum sensing in E. coli. Mol Microbiol 43: 809–821. Link to PubMed

• Sperandio, 1999 V. Sperandio, J.L. Mellies, W. Nguyen, S. Shin and J.B. Kaper, Quorum sensing controls expression of the type III secretion gene transcription and protein secretion in enterohemorrhagic and enteropathogenic Escherichia coli. Proc. Natl. Acad. Sci. USA, 96 (1999), pp. 15196–15201.Article Link

• Sperandio, 2000 V. Sperandio, J.L. Mellies, R.M. Delahay, G. Frankel, J.A. Crawford, W. Nguyen and J.B. Kaper, Activation of enteropathogenic Escherichia coli (EPEC) LEE2 and LEE3 operons by Ler. Mol. Microbiol., 38 (2000), pp. 781–793. Link to PubMed

• Sperandio, 2001 V. Sperandio, A.G. Torres, J.A. Giron and J.B. Kaper, Quorum sensing is a global regulatory mechanism in enterohemorrhagic Escherichia coli O157:H7. J. Bacteriol., 183 (2001), pp. 5187–5197. Article link

• Steidler L, Hans W, Schotte L, Neirynck S, Obermeier F, Falk W, Fiers W, Remaut E. Treatment of murine colitis by Lactococcus lactis secreting interleukin-10, Science 289. 2000. 1352–1355. Link to Pubmed

• T. B. Bartnikas,† I. E. Tosques, W. P. Laratta, J. Shi and J. P. Shapleigh. 1997. Characterization of the Nitric Oxide Reductase-Encoding Region in Rhodobacter sphaeroides 2.4.3. J. Bacteriol. 179: 3534–3540. Link to PubMed

• V.M. Sanders, R.A. Baker, D.S. Ramer-Quinn, D.J. Kasprowicz, B.A. Fuchs and N.E. Street, Differential expression of the beta2-adrenergic receptor by Th1 and Th2 clones: implications for cytokine production and B cell help. J. Immunol., 158 (1997), pp. 4200–4210. Link to PubMed