Skip to main content

Advertisement

SpringerLink
Log in

Bacteria-mediated disease therapy

  • Mini-Review
  • Published:
Applied Microbiology and Biotechnology Aims and scope Submit manuscript

Abstract

Laboratory bacteria have been model systems for studying gene function or developing molecular biotechnologies; industrial bacteria have been used to produce drugs, foods, fuel etc.; while pathogenic bacteria have been the subject of infectious diseases studies with aim of controlling them. Recently, with our increasing knowledge in molecular biology, bacterial genetics, and immunology, bacteria have gained increased interest in therapeutic applications. This review will summarize recent advances toward applying bacteria in treatment of diseases, such as inflammatory disease, cancer, and virus infection. Probiotics have long been appreciated for their immunomodulatory effect, which are discussed in the anti-inflammatory section. Anaerobic bacteria have been applied for destructing tumor cells or used as a magic bullet to specifically deliver therapeutic agents to tumor tissue. Examples and strategies of applying those tumor-targeting bacteria are discussed in the antitumor section. Finally, the pioneer study of applying Salmonella in delivering RNase P that was specifically engineered to target essential mRNAs of virus is summarized.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Agorio C, Schreiber F, Sheppard M, Mastroeni P, Fernandez M, Martinez MA, Chabalgoity JA (2007) Live attenuated Salmonella as a vector for oral cytokine gene therapy in melanoma. J Gene Med 9:416–423

    Article  CAS  Google Scholar 

  • Agrawal N, Bettegowda C, Cheong I, Geschwind JF, Drake CG, Hipkiss EL, Tatsumi M, Dang LH, Diaz LA Jr, Pomper M, Abusedera M, Wahl RL, Kinzler KW, Zhou S, Huso DL, Vogelstein B (2004) Bacteriolytic therapy can generate a potent immune response against experimental tumors. Proc Natl Acad Sci U S A 101:15172–15177

    Article  CAS  Google Scholar 

  • Arrach N, Zhao M, Porwollik S, Hoffman RM, McClelland M (2008) Salmonella promoters preferentially activated inside tumors. Cancer Res 68:4827–4832

    Article  CAS  Google Scholar 

  • Bai Y, Gong H, Li H, Vu GP, Lu S, Liu F (2011) Oral delivery of RNase P ribozymes by Salmonella inhibits viral infection in mice. Proc Natl Acad Sci U S A 108:3222–3227

    Article  CAS  Google Scholar 

  • Bermudes D, Low B, Pawelek J (2000) Tumor-targeted Salmonella. Highly selective delivery vectors. Adv Exp Med Biol 465:57–63

    Article  CAS  Google Scholar 

  • Capurso G, Marignani M, Piciucchi M, Merola E, Delle Fave G (2008) Probiotics and severe acute pancreatitis. J Clin Gastroenterol 42(Suppl 3 Pt 1):S148–S151

    Article  Google Scholar 

  • Castanotto D, Rossi JJ (2009) The promises and pitfalls of RNA-interference-based therapeutics. Nature 457:426–433

    Article  CAS  Google Scholar 

  • Catlett-Falcone R, Dalton WS, Jove R (1999) STAT proteins as novel targets for cancer therapy. Curr Opin Oncol 11:490–496

    Article  CAS  Google Scholar 

  • Cheong I, Huang X, Bettegowda C, Diaz LA Jr, Kinzler KW, Zhou S, Vogelstein B (2006) A bacterial protein enhances the release and efficacy of liposomal cancer drugs. Science 314:1308–1311

    Article  CAS  Google Scholar 

  • Dang LH, Bettegowda C, Huso DL, Kinzler KW, Vogelstein B (2001) Combination bacteriolytic therapy for the treatment of experimental tumors. Proc Natl Acad Sci U S A 98:15155–15160

    Article  CAS  Google Scholar 

  • De Winter H, Cheroutre H, Kronenberg M (1999) Mucosal immunity and inflammation. II. The yin and yang of T cells in intestinal inflammation: pathogenic and protective roles in a mouse colitis model. Am J Physiol 276:G1317–G1321

    Google Scholar 

  • Di Giacinto C, Marinaro M, Sanchez M, Strober W, Boirivant M (2005) Probiotics ameliorate recurrent Th1-mediated murine colitis by inducing IL-10 and IL-10-dependent TGF-beta-bearing regulatory cells. J Immunol 174:3237–3246

    Google Scholar 

  • Elson CO, Cong Y, Weaver CT, Schoeb TR, McClanahan TK, Fick RB, Kastelein RA (2007) Monoclonal anti-interleukin 23 reverses active colitis in a T cell-mediated model in mice. Gastroenterology 132:2359–2370

    Article  CAS  Google Scholar 

  • Epaulard O, Toussaint B, Quenee L, Derouazi M, Bosco N, Villiers C, Le Berre R, Guery B, Filopon D, Crombez L, Marche PN, Polack B (2006) Anti-tumorimmunotherapy via antigen delivery from a live attenuated genetically engineered Pseudomonas aeruginosa type III secretion system-based vector. Mol Ther 14:656–661

    Article  CAS  Google Scholar 

  • Finlay BB, McFadden G (2006) Anti-immunology: evasion of the host immune system by bacterial and viral pathogens. Cell 124:767–782

    Article  CAS  Google Scholar 

  • Frank DN, St Amand AL, Feldman RA, Boedeker EC, Harpaz N, Pace NR (2007) Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci U S A 104:13780–13785

    Article  CAS  Google Scholar 

  • Gardlik R, Behuliak M, Palffy R, Celec P, Li CJ (2011) Gene therapy for cancer: bacteria-mediated anti-angiogenesis therapy. Gene Ther 18:425–431

    Article  CAS  Google Scholar 

  • Guslandi M, Mezzi G, Sorghi M, Testoni PA (2000) Saccharomyces boulardii in maintenance treatment of Crohn’s disease. Dig Dis Sci 45:1462–1644

    Article  CAS  Google Scholar 

  • Heisig M, Frentzen A, Bergmann B, Galmbacher K, Gentschev I, Hotz C, Schoen C, Stritzker J, Fensterle J, Rapp UR, Goebel W (2011) Specific antibody-receptor interactions trigger InlAB-independent uptake of Listeria monocytogenes into tumor cell lines. BMC Microbiol 11:163

    Article  CAS  Google Scholar 

  • Hess J, Grode L, Hellwig J, Conradt P, Gentschev I, Goebel W, Ladel C, Kaufmann SH (2009) Protection against murine tuberculosis by an attenuated recombinant Salmonella typhimurium vaccine strain that secretes the 30-kDa antigen of Mycobacterium bovis BCG. FEMS Immunol Med Microbiol 27:283–289

    Article  Google Scholar 

  • Hooper LV, Gordon JI (2001) Commensal host-bacterial relationships in the gut. Science 292:1115–1118

    Article  CAS  Google Scholar 

  • Khan SA, Everest P, Servos S, Foxwell N, Zähringer U, Brade H, Rietschel ET, Dougan G, Charles IG, Maskell DJ (1998) A lethal role for lipid A in Salmonella infections. Mol Microbiol 29:571–579

    Article  CAS  Google Scholar 

  • Kimura NT, Taniguchi S, Aoki K, Baba T (1980) Selective localization and growth of Bifidobacterium bifidum in mouse tumours following intravenous administration. Cancer Res 40:2061–2068

    CAS  Google Scholar 

  • Kruis W, Schut E, Fric P, Fixa B, Judmaier G, Stolte M (1997) Double-blind comparison of an oral Escherichia coli preparation and mesalazine in maintaining remission of ulcerative colitis. Aliment Pharmacol Ther 11:853–858

    Article  CAS  Google Scholar 

  • Lee CH, Wu CL, Shiau AL (2004) Endostatin gene therapy delivered by Salmonella choleraesuis in murine tumor models. J Gene Med 6:1382–1393

    Article  CAS  Google Scholar 

  • Lee JS, Paek NS, Kwon OS, Hahm KB (2010) Anti-inflammatory actions of probiotics through activating suppressor of cytokine signaling (SOCS) expression and signaling in Helicobacter pylori infection: a novel mechanism. J Gastroenterol Hepatol 25:194–202

    Article  CAS  Google Scholar 

  • Li Y, Guo K, Chen H, Xie Y, Song C, Xun T, Ren D (2001) Oral cytokine gene therapy against murine tumor using attenuated Salmonella typhimurium. Int J Cancer 94:438–443

    Article  CAS  Google Scholar 

  • Loguercio C, Federico A, Tuccillo C, Terracciano F, D'Auria MV, De Simone C, Del Vecchio BC (2005) Beneficial effect of a probiotic VSL#3 on parameters of liver dysfunction in chronic liver diseases. J Clin Gastroenterol 39:540–543

    Article  Google Scholar 

  • Low KB, Ittensohn M, Le T, Platt J, Sodi S, Amoss M, Ash O, Carmichael E, Chakraborty A, Fischer J, Lin SL, Luo X, Miller SI, Zheng L, King I, Pawelek JM, Bermudes D (1999) Lipid A mutant Salmonella with suppressed virulence and TNF alpha induction retain tumour-targeting in vivo. Nat Biotechnol 17:37–41

    CAS  Google Scholar 

  • Low KB, Ittensohn M, Luo X, Zheng LM, King I, Pawelek JM, Bermudes D (2004) Construction of VNP20009: a novel, genetically stable antibiotic-sensitive strain of tumor-targeting Salmonella for parenteral administration in humans. Methods Mol Med 90:47–60

    CAS  Google Scholar 

  • Luo Y, Knudson MJ (2010) Mycobacterium bovis bacillus Calmette–Guérin-induced macrophage cytotoxicity against bladder cancer cells. Clin Dev Immunol 2010:357591

    Article  Google Scholar 

  • Madsen K, Cornish A, Soper P, McKaigney C, Jijon H, Yachimec C, Doyle J, Jewell L, De Simone C (2001) Probiotic bacteria enhance murine and human intestinal epithelial barrier function. Gastroenterology 121:580–591

    Article  CAS  Google Scholar 

  • Malmgren R, Flanigan C (1955) Localisation of the vegetative form of Clostridium tetani in mouse tumours following intravenous spore administration. Cancer Res 15:473–478

    CAS  Google Scholar 

  • Mazmanian SK, Liu CH, Tzianabos AO, Kasper DL (2005) An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell 122:107–118

    Article  CAS  Google Scholar 

  • Mills E, Baruch K, Charpentier X, Kobi S, Rosenshine I (2008) Real-time analysis of effector translocation by the type III secretion system of enteropathogenic Escherichia coli. Cell Host Microbe 3:104–113

    Article  CAS  Google Scholar 

  • Mora LB, Buettner R, Seigne J, Diaz J, Ahmad N, Garcia R, Bowman T, Falcone R, Fairclough R, Cantor A, Muro-Cacho C, Livingston S, Karras J, Pow-Sang J, Jove R (2002) Constitutive activation of Stat3 in human prostate tumors and cell lines: direct inhibition of Stat3 signaling induces apoptosis of prostate cancer cells. Cancer Res 62:6659–6666

    CAS  Google Scholar 

  • Möse JR, Möse G (1964) Oncolysis by Clostridia I. Activity of Clostridium butyricum (M-55) and other nonpathogenic Clostridia against the Ehrlich carcinoma. Cancer Res 24:212–216

    Google Scholar 

  • Nuyts S, Van Mellaert L, Theys J, Landuyt W, Bosmans E, Anné J, Lambin P (2001) Radio-responsive recA promoter significantly increases TNF alpha production in recombinant clostridia after 2 Gy irradiation. Gene Ther 8:1197–1201

    Article  CAS  Google Scholar 

  • O'Mahony C, Scully P, O'Mahony D, Murphy S, O'Brien F, Lyons A, Sherlock G, MacSharry J, Kiely B, Shanahan F, O'Mahony L (2008) Commensal-induced regulatory T cells mediate protection against pathogen stimulated NF-κB activation. PLoS Pathog 4:e1000112

    Article  Google Scholar 

  • Pálffy R, Gardlík R, Hodosy J, Behuliak M, Resko P, Radvánský J, Celec P (2006) Bacteria in gene therapy: bactofection versus alternative gene therapy. Gene Ther 13:101–105

    Article  Google Scholar 

  • Park S, Kim WS, Choi UJ, Han SU, Kim YS, Kim YB, Chung MH, Nam KT, Kim DY, Cho SW, Hahm KB (2004) Amelioration of oxidative stress with ensuing inflammation contributes to chemoprevention of H. pylori-associated gastric carcinogenesis. Antioxid Redox Signal 6:549–560

    Article  CAS  Google Scholar 

  • Park KT, Allen AJ, Bannantine JP, Seo KS, Hamilton MJ, Abdellrazeq GS, Rihan HM, Grimm A, Davis WC (2011) Evaluation of two mutants of Mycobacterium avium subsp. paratuberculosis as candidates for a live attenuated vaccine for Johne’s disease. Vaccine 29:4709–4719

    Article  CAS  Google Scholar 

  • Pawelek JM, Brooks Low K, Bermudes D (1997) Tumour-targeted Salmonella as a novel anticancer vector. Cancer Res 57:4537–4544

    CAS  Google Scholar 

  • Penner R, Fedorak RN, Madsen KL (2005) Probiotics and nutraceuticals: non-medicinal treatments of gastrointestinal diseases. Curr Opin Pharmacol 5:596–603

    Article  CAS  Google Scholar 

  • Podolsky DK (2002) Inflammatory bowel disease. N Engl J Med 347:417–429

    Article  CAS  Google Scholar 

  • Prantera C, Scribano ML, Falasco G, Andreoli A, Luzi C (2002) Ineffectiveness of probiotics in preventing recurrence after curative resection for Crohn’s disease: a randomised controlled trial with Lactobacillus GG. Gut 51:405–409

    Article  CAS  Google Scholar 

  • Quagliarello V, Scheld WM (1992) Bacterial meningitis: pathogenesis, pathophysiology, and progress. N Engl J Med 327:864–872

    Article  CAS  Google Scholar 

  • Redpath S, Ghazal P, Gascoigne NR (2001) Hijacking and exploitation of IL-10 by intracellular pathogens. Trends Microbiol 9:86–92

    Article  CAS  Google Scholar 

  • Rembacken BJ, Snelling AM, Hawkey PM, Chalmers DM, Axon AT (1999) Non-pathogenic Escherichia coli versus mesalazine for the treatment of ulcerative colitis: a randomised trial. Lancet 354:635–639

    Article  CAS  Google Scholar 

  • Round JL, Mazmanian SK (2009) The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol 9:313–323

    Article  CAS  Google Scholar 

  • Ryan RM, Green J, Lewis CE (2005) Use of bacteria in anti-cancer therapies. Bioessays 28:84–94

    Article  Google Scholar 

  • Sanchez J, Holmgren J (2011) Cholera toxin—a foe & a friend. Indian J Med Res 133:153–163

    CAS  Google Scholar 

  • Sasaki T, Fujimori M, Hamaji Y, Hama Y, Ito K, Amano J, Taniguchi S (2006) Genetically engineered Bifidobacterium longum for tumor-targeting enzyme-prodrug therapy of autochthonous mammary tumors in rats. Cancer Sci 97:649–657

    Article  CAS  Google Scholar 

  • Scherer LJ, Rossi JJ (2003) Approaches for the sequence-specific knockdown of mRNA. Nat Biotechnol 21:1457–1465

    Article  CAS  Google Scholar 

  • Schultz M, Veltkamp C, Dieleman LA, Grenther WB, Wyrick PB, Tonkonogy SL, Sartor RB (2002) Lactobacillus plantarum 299V in the treatment and prevention of spontaneous colitis in interleukin-10-deficient mice. Inflamm Bowel Dis 8:71–80

    Article  Google Scholar 

  • Shahabi V, Maciag PC, Rivera S, Wallecha A (2010) Live, attenuated strains of Listeria and Salmonella as vaccine vectors in cancer treatment. Bioeng Bugs 1:235–239

    Google Scholar 

  • Simpson SJ, de Jong YP, Comiskey M, Terhorst C (2000) Pathways of T cell pathology in models of chronic intestinal inflammation. Int Rev Immunol 19:1–37

    Article  CAS  Google Scholar 

  • Sokol H, Pigneur B, Watterlot L, Lakhdari O, Bermúdez-Humarán LG, Gratadoux JJ, Blugeon S, Bridonneau C, Furet JP, Corthier G, Grangette C, Vasquez N, Pochart P, Trugnan G, Thomas G, Blottière HM, Doré J, Marteau P, Seksik P, Langella P (2008) Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc Natl Acad Sci U S A 105:16731–16736

    Article  CAS  Google Scholar 

  • Stöber H, Maier E, Schmidt H (2010) Protective effects of Lactobacilli, Bifidobacteria and Staphylococci on the infection of cultured HT29 cells with different enterohemorrhagic Escherichia coli serotypes are strain-specific. Int J Food Microbiol 144:133–140

    Article  Google Scholar 

  • Stritzker J, Weibel S, Hill PJ, Oelschlaeger TA, Goebel W, Szalay AA (2007) Tumor-specific colonization, tissue distribution, and gene induction by probiotic Escherichia coli Nissle 1917 in live mice. Int J Med Microbiol 297:151–162

    Article  CAS  Google Scholar 

  • Stritzker J, Pilgrim S, Szalay AA, Goebel W (2008) Prodrug converting enzyme gene delivery by L. monocytogenes. BMC Cancer 8:94

    Article  Google Scholar 

  • Terradot L, Waksman G (2011) Architecture of the Helicobacter pylori Cag-type IV secretion system. FEBS J 278:1213–1222

    Article  CAS  Google Scholar 

  • Wei MQ, Ellem KA, Dunn P, West MJ, Bai CX, Vogelstein B (2006) Facultative or obligate anaerobic bacteria have the potential for multimodality therapy of solid tumours. Eur J Cancer 43:490–496

    Article  Google Scholar 

  • Wood LM, Pan ZK, Guirnalda P, Tsai P, Seavey M, Paterson Y (2011) Targeting tumor vasculature with novel Listeria-based vaccines directed against CD105. Cancer Immunol Immunother 60:931–942

    Article  CAS  Google Scholar 

  • Xiang R, Lode HN, Chao TH, Ruehlmann JM, Dolman CS, Rodriguez F, Whitton JL, Overwijk WW, Restifo NP, Reisfeld RA (2000) An autologous oral DNA vaccine protects against murine melanoma. Proc Natl Acad Sci U S A 97:5492–5497

    Article  CAS  Google Scholar 

  • Xiang S, Fruehauf J, Li CJ (2006) Short hairpin RNA-expressing bacteria elicit RNA interference in mammals. Nat Biotechnol 24:697–702

    Article  CAS  Google Scholar 

  • Xiang R, Luo Y, Niethammer AG, Reisfeld RA (2008) Oral DNA vaccines target the tumor vasculature and microenvironment and suppress tumor growth and metastasis. Immunol Rev 222:117–128

    Article  CAS  Google Scholar 

  • Yang N, Li SH, Lü YZ, Chen LS, Ren DM (2011) Attenuated Salmonella typhimurium carrying shRNA-expressing vectors elicit RNA interference in murine bladder tumors. Acta Pharmacol Sin 32:368–374

    Article  CAS  Google Scholar 

  • Yazawa K, Fujimori M, Amano J, Kano Y, Taniguchi S (2000) Bifidobacterium longum as a delivery system for cancer gene therapy: selective localization and growth in hypoxic tumours. Cancer Gene Ther 7:269–274

    Article  CAS  Google Scholar 

  • Yoon WS, Chae YS, Hong J, Park YK (2011) Antitumor therapeutic effects of a genetically engineered Salmonella typhimurium harboring TNF-α in mice. Appl Microbiol Biotechnol 89:1807–1819

    Article  CAS  Google Scholar 

  • Yu H, Kim KS (2010) Ferredoxin is involved in secretion of cytotoxic necrotizing factor 1 across the cytoplasmic membrane in Escherichia coli K1. Infect Immun 78:838–844

    Article  CAS  Google Scholar 

  • Yu H, Kim KS (2011) The involvement of SelB in expression of cytotoxic necrotizing factor 1 in Escherichia coli. FEBS Lett 585:1934–1940

    Article  CAS  Google Scholar 

  • Yu H, Peng W, Liu Y, Wu T, Yao Y, Cui M, Jiang W, Zhao G (2006) Identification and characterization of glnA promoter and its corresponding trans-regulatory protein GlnR in the rifamycin SV producing actinomycete, Amycolatopsis mediterranei U32. Acta Biochim Biophys Sin 38:831–843

    Article  CAS  Google Scholar 

  • Yu H, Yao Y, Liu Y, Jiao R, Jiang W, Zhao G (2007) A complex role of Amycolatopsis mediterranei GlnR in nitrogen metabolism and related antibiotics production. Arch Microbiol 188:89–96

    Article  CAS  Google Scholar 

  • Yuksel ZS, Buber E, Kocagoz T, Alp A, Saribas Z, Acan NL (2011) Mycobacterial strains that stimulate the immune system most efficiently as candidates for the treatment of bladder cancer. J Mol Microbiol Biotechnol 20:24–28

    Article  CAS  Google Scholar 

  • Zhang L, Gao L, Zhao L, Guo B, Ji K, Tian Y, Wang J, Yu H, Hu J, Kalvakolanu DV, Kopecko DJ, Zhao X, Xu DQ (2007) Intratumoral delivery and suppression of prostate tumor growth by attenuated Salmonella enterica serovar typhimurium carrying plasmid-based small interfering RNAs. Cancer Res 67:5859–5864

    Article  CAS  Google Scholar 

  • Zhao M, Yang M, Li XM, Jiang P, Baranov E, Li S, Xu M, Penman S, Hoffman RM (2005) Tumor-targeting bacterial therapy with amino acid auxotrophs of GFP-expressing Salmonella typhimurium. Proc Natl Acad Sci U S A 102:755–760

    Article  CAS  Google Scholar 

Download references

Acknowledgment

The author would like to give thanks to Prof. Alexander Steinbüchel for the helpful suggestions in preparing the manuscripts.

Author information

Authors and Affiliations

  1. Division of Pediatric Infectious Diseases, Johns Hopkins University School of Medicine, 720 Rutland Ave, Ross 1109, Baltimore, MD, 21205, USA

    Hao Yu

Authors
  1. Hao Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hao Yu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yu, H. Bacteria-mediated disease therapy. Appl Microbiol Biotechnol 92, 1107–1113 (2011). https://doi.org/10.1007/s00253-011-3648-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00253-011-3648-x

Keywords

Search

Navigation