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  • 1 Molecular Microbiology and Genomics Consultants, Germany
  • 2 Institute of Medical Microbiology and Hygiene, Germany
  • 3 vermicon AG, Germany
  • 4 Berlin, Germany
  • 5 Center for Biological Sequence Analysis, Department of Systems Biology, Denmark
  • 6 SymbioPharm GmbH, Germany
  • 7 GlaxoSmithKline Biologicals, Germany
Open access

The probiotic product Symbioflor2 (DSM 17252) is a bacterial concentrate of six different Escherichia coli genotypes, whose complete genome sequences are compared here, between each other as well as to other E. coli genomes. The genome sequences of Symbioflor2 E. coli components contained a number of virulence-associated genes. Their presence seems to be in conflict with a recorded history of safe use, and with the observed low frequency of adverse effects over a period of more than 6 years. The genome sequences were used to identify unique sequences for each component, for which strain-specific hybridization probes were designed. A colonization study was conducted whereby five volunteers were exposed to an exceptionally high single dose. The results showed that the probiotic E. coli could be detected for 3 months or longer in their stools, and this was in particular the case for those components containing higher numbers of virulence-associated genes. Adverse effects from this long-term colonization were absent. Thus, the presence of the identified virulence genes does not result in a pathogenic phenotype in the genetic background of these probiotic E. coli.

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  • Littlejohn TG, DiBerardino D, Messerotti LJ, Spiers SJ, Skurray RA: Structure and evolution of a family of genes encoding antiseptic and disinfectant resistance in Staphylococcus aureus. Gene 101, 59–66 (1991)

  • Wassenaar TM, Gaastra W: Bacterial virulence, where to draw the line? FEMS Microbiol Letters 201, 1–7 (2001)

  • Wassenaar TM, Alter T (2012): Virulence genes in microbial risk assessment of probiotic organisms: what do genome sequences tell us? In: Beneficial microorganisms in agriculture, food and the environment, eds. Sundh I, Goettel M, Wilckes A, CABI, pp. 180–196

  • Wassenaar TM, Bohlin J, Binnewies TT, Ussery DW: Genome comparison of bacterial pathogens. Genome Dyn 6, 1–20 (2009)

  • Willenbrock H, Hallin PF, Wassenaar TM, Ussery DW: Characterization of probiotic Escherichia coli isolates with a novel pan-genome microarray. Genome Biol 8, R267 (2007)

  • Sonnenborn U, Schulze J: The non-pathogenic Escherichia coli strain Nissle 1917 — features of a versatile probiotic. Microb Ecol Health Dis 21, 122–158 (2009)

  • Grozdanov L, Raasch C, Schulze J, Sonnenborn U, Gottschalk G, Hacker, J Dobrindt U: Analysis of the genome structure of the nonpathogenic probiotic Escherichia coli strain Nissle 1917. J Bacteriol 186, 5432–5441 (2004)

  • Hancock V, Vejborg RM, Klemm P: Functional genomics of probiotic Escherichia coli Nissle 1917 and 83972, and UPEC strain CFT073: comparison of transcriptomes, growth and biofilm formation. Mol Genet Genomics 284, 437–454 (2010)

  • Lukjancenko O, Wassenaar TM, Ussery DW: Comparison of 61 sequenced Escherichia coli genomes. Microb Ecol 60, 708–720 (2010)

  • Zschüttig A, Auerbach C, Meltke S, Eichhorn C, Brandt M, Blom J, Goesmann A, Jarek M, Scharfe M, Zimmermann K, Wassenaar TM, and Gunzer F: Complete sequence of probiotic Symbioflor2 E. coli strain G3/10 and draft sequences of Symbioflor2 strains G1/2, G4/9, G5, G6/7 and G8. Submitted to Genome Announcement

  • Vesth T, Lagesen K, Acar O, Ussery D: CMG-Biotools, a Free Workbench for Basic Comparative Microbial Genomics. PLoS One 8, e60120 (2013)

  • Snipen L, Ussery DW: Standard operating procedure for computing pangenome trees. Stand Genomic Sci 2, 135–141 (2010)

  • Zhou CE, Smith J, Lam M, Zemla A, Dyer MD, Slezak T: MvirDB-a microbial database of protein toxins, virulence factors and antibiotic resistance genes for bio-defence applications. Nucl Acids Res 35 (Database issue), D391–D394 (2006)

  • Chen LH, Xiong ZH, Sun LL, Yang J and Jin Q: VFDB 2012 update: toward the genetic diversity and molecular evolution of bacterial virulence factors. Nucleic Acids Res 40 (Database issue), D641–D645 (2012)

  • Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ: Basic local alignment search tool. J Mol Biol 215, 403–410 (1990)

  • Elvers KT, Helps CR, Wassenaar TM, Allen VM, Newell DG: Development of a strain-specific molecular method for quantitating individual campylobacter strains in mixed populations. Appl Environ Microbiol 74, 2321–2331 (2008)

  • Zschüttig A, Zimmermann K, Blom J, Goesmann A, Pöhlmann C, Gunzer F: Identification and characterization of microcin S, a new antibacterial peptide produced by probiotic Escherichia coli G3/10. PLoS One 7, e33351 (2012)

  • Maiden MC, Bygraves JA, Feil E, Morelli G, Russell JE, Urwin R, Zhang Q, Zhou J, Zurth K, Caugant DA, Feavers IM, Achtman M, Spratt BG: Multilocus sequence typing: a portable approach to the identification of clones within populations of pathogenic microorganisms. Proc Natl Acad Sci USA 95, 3140–3145 (1998)

  • Monteiro C, Saxena I, Wang X, Kader A, Bokranz W, Simm R, Nobles D, Chromek M, Brauner A, Brown RM Jr., Römling U: Characterization of cellulose production in Escherichia coli Nissle 1917 and its biological consequences. Environ Microbiol 11, 1105–1116 (2009)

  • Linke D, Riess T, Autenrieth IB, Lupas A, Kempf VA: Trimeric autotransporter adhesins: variable structure, common function. Trends Microbiol 14, 264–270 (2006)

  • Al-Hasani K, Henderson IR, Sakellaris H, Rajakumar K, Grant T, Nataro JP, Robins-Browne R, Adler B: The sigA gene which is borne on the she pathogenicity island of Shigella flexneri 2a encodes an exported cytopathic protease involved in intestinal fluid accumulation. Infect Immun 68, 2457–2463 (2000)

  • Bücker R, Schulz E, Günzel D, Bojarski C, Lee IF, John LJ, Wiegand S, Janßen T, Wieler LH, Dobrindt U, Beutin L, Ewers C, Fromm M, Siegmund B, Troeger H, Schulzke JD: a-Haemolysin of Escherichia coli in IBD: a potentiator of inflammatory activity in the colon. Gut 63, 1893–1901 (2014)

  • Mahan MJ, Heithoff DM, Sinsheimer RL, Low DA: Assessment of bacterial pathogenesis by analysis of gene expression in the host. Annu Rev Genet 34, 139–164 (2000)

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