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Functional genomics of probiotic Escherichia coli Nissle 1917 and 83972, and UPEC strain CFT073: comparison of transcriptomes, growth and biofilm formation

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Abstract

Strain CFT073 is a bona fide uropathogen, whereas strains 83972 and Nissle 1917 are harmless probiotic strains of urinary tract and faecal origin, respectively. Despite their different environmental origins and dispositions the three strains are very closely related and the ancestors of 83972 and Nissle 1917 must have been very similar to CFT073. Here, we report the first functional genome profiling of Nissle 1917 and the first biofilm profiling of a uropathogen. Transcriptomic profiling revealed that Nissle 1917 expressed many UPEC-associated genes and showed that the active genomic profiles of the three strains are closely related. The data demonstrate that the distance from a pathogen to a probiotic strain can be surprisingly short. We demonstrate that Nissle 1917, in spite of its intestinal niche origin, grows well in urine, and is a good biofilm former in this medium in which it also out-competes CFT073 during planktonic growth. The role in biofilm formation of three up-regulated genes, yhaK, yhcN and ybiJ, was confirmed by knockout mutants in Nissle 1917 and CFT073. Two of these mutants CFT073∆yhcN and CFT073∆ybiJ had significantly reduced motility compared with the parent strain, arguably accounting for the impaired biofilm formation. Although the three strains have very different strategies vis-à-vis the human host their functional gene profiles are surprisingly similar. It is also interesting to note that the only two Escherichia coli strains used as probiotics are in fact deconstructed pathogens.

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References

  • Andersson P, Engberg I, Lidin-Janson G, Lincoln K, Hull R, Hull S, Svanborg C (1991) Persistence of Escherichia coli bacteriuria is not determined by bacterial adherence. Infect Immun 59:2915–2921

    CAS  PubMed  Google Scholar 

  • Beloin C, Valle J, Latour-Lambert P, Faure P, Kzreminski M, Balestrino D, Haagensen JA, Molin S, Prensier G, Arbeille B, Ghigo JM (2004) Global impact of mature biofilm lifestyle on Escherichia coli K-12 gene expression. Mol Microbiol 51:659–674

    Article  CAS  PubMed  Google Scholar 

  • Brzuszkiewicz E, Brüggemann H, Liesegang H, Emmerth M, Ölschläger T, Nagy G, Albermann K, Wagner C, Buchrieser C, Emody L, Gottschalk G, Hacker J, Dobrindt U (2006) How to become a uropathogen: comparative genomic analysis of extraintestinal pathogenic Escherichia coli strains. Proc Natl Acad Sci USA 103:12879–12884

    Article  PubMed  Google Scholar 

  • Chen SL, Hung CS, Xu J, Reigstad CS, Magrini V, Sabo A, Blasiar D, Bieri T, Meyer RR, Ozersky P, Armstrong JR, Fulton RS, Latreille JP, Spieth J, Hooton TM, Mardis ER, Hultgren SJ, Gordon JI (2006) Identification of genes subject to positive selection in uropathogenic strains of Escherichia coli: a comparative genomics approach. Proc Natl Acad Sci USA 103:5977–5982

    Article  CAS  PubMed  Google Scholar 

  • Chouikha I, Germon P, Brée A, Gilot P, Moulin-Schouleur M, Schouler C (2006) A selC-associated genomic island of the extraintestinal avian pathogenic Escherichia coli strain BEN2908 is involved in carbohydrate uptake and virulence. J Bacteriol 188:977–987

    Article  CAS  PubMed  Google Scholar 

  • Christensen BB, Sternberg C, Andersen JB, Palmer RJ Jr, Nielsen AT, Givskov M, Molin S (1999) Molecular tools for study of biofilm physiology. Methods Enzymol 310:20–42

    Article  CAS  PubMed  Google Scholar 

  • Costerton JW, Lewandowski Z, Caldwell DE, Korber DR, Lappin-Scott HM (1995) Microbial biofilms. Annu Rev Microbiol 49:711–745

    Article  CAS  PubMed  Google Scholar 

  • Costerton JW, Stewart PS, Greenberg EP (1999) Bacterial biofilms: a common cause of persistent infections. Science 284:1318–1322

    Article  CAS  PubMed  Google Scholar 

  • Datsenko KA, Wanner BL (2000) One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products. Proc Natl Acad Sci USA 97:6640–6645

    Article  CAS  PubMed  Google Scholar 

  • Domka J, Lee J, Wood TK (2006) YliH (BssR) and YceP (BssS) regulate Escherichia coli K-12 biofilm formation by influencing cell signaling. Appl Environ Microbiol 72:2449–2459

    Article  CAS  PubMed  Google Scholar 

  • Ferrières L, Hancock V, Klemm P (2007) Biofilm exclusion of uropathogenic bacteria by selected asymptomatic bacteriuria Escherichia coli strains. Microbiology 153:1711–1719

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Gurmu D, Lu J, Johnson KA, Nordlund P, Holmgren A, Erlandsen H (2009) The crystal structure of the protein YhaK from Escherichia coli reveals a new subclass of redox sensitive enterobacterial bicupins. Proteins 74:18–31

    Article  CAS  PubMed  Google Scholar 

  • Hagan EC, Mobley HL (2007) Uropathogenic Escherichia coli outer membrane antigens expressed during urinary tract infection. Infect Immun 75:3941–3949

    Article  CAS  PubMed  Google Scholar 

  • Hancock V, Klemm P (2007) Global gene expression profiling of asymptomatic bacteriuria Escherichia coli during biofilm growth in human urine. Infect Immun 75:966–976

    Article  CAS  PubMed  Google Scholar 

  • Hancock V, Ferrières L, Klemm P (2007) Biofilm formation by asymptomatic and virulent urinary tract infectious Escherichia coli strains. FEMS Microbiol Lett 267:30–37

    Article  CAS  PubMed  Google Scholar 

  • Hancock V, Ferrières L, Klemm P (2008a) The ferric yersiniabactin uptake receptor FyuA is required for efficient biofilm formation by urinary tract infectious Escherichia coli in human urine. Microbiology 154:167–175

    Article  CAS  PubMed  Google Scholar 

  • Hancock V, Seshasayee AS, Ussery DW, Luscombe NM, Klemm P (2008b) Transcriptomics and adaptive genomics of the asymptomatic bacteriuria Escherichia coli strain 83972. Mol Gen Genet 279:523–534

    CAS  Google Scholar 

  • Hancock V, Dahl M, Klemm P (2010) Probiotic Escherichia coli strain Nissle 1917 out-competes intestinal pathogens during biofilm formation. J Med Microbiol 59:392–399

    Article  PubMed  Google Scholar 

  • Hull R, Rudy D, Donovan W, Svanborg C, Wieser I, Stewart C, Darouiche R (2000) Urinary tract infection prophylaxis using Escherichia coli 83972 in spinal cord injured patients. J Urol 163:872–877

    Article  CAS  PubMed  Google Scholar 

  • Johnson JR, Delavari P, Kuskowski M, Stell AL (2001) Phylogenetic distribution of extraintestinal virulence-associated traits in Escherichia coli. J Infect Dis 183:78–88

    Article  CAS  PubMed  Google Scholar 

  • Junker LM, Peters JE, Hay AG (2006) Global analysis of candidate genes important for fitness in a competitive biofilm using DNA-array-based transposon mapping. Microbiology 152:2233–2245

    Article  CAS  PubMed  Google Scholar 

  • Kim T-J, Young BM, Young GM (2008) Effect of flagellar mutations on Yersinia enterocolitica biofilm formation. Appl Environ Microbiol 74:5466–5474

    Article  CAS  PubMed  Google Scholar 

  • Kirov SM, Castrisios M, Shaw JG (2004) Aeromonas flagella (polar and lateral) are enterocyte adhesins that contribute to biofilm formation on surfaces. Infect Immun 72:1939–1945

    Article  CAS  PubMed  Google Scholar 

  • Klemm P, Roos V, Ulett GC, Svanborg C, Schembri MA (2006) Molecular characterization of the Escherichia coli asymptomatic bacteriuria strain 83972: the taming of a pathogen. Infect Immun 74:781–785

    Article  CAS  PubMed  Google Scholar 

  • Klemm P, Hancock V, Schembri MA (2007) Mellowing out: adaptation to commensalism by Escherichia coli asymptomatic bacteriuria strain 83972. Infect Immun 75:3688–3695

    Article  CAS  PubMed  Google Scholar 

  • Lasaro MA, Salinger N, Zhang J, Wang Y, Zhong Z, Goulian M, Zhu J (2009) F1C fimbriae play an important role in biofilm formation and intestinal colonization by the Escherichia coli commensal strain Nissle 1917. Appl Environ Microbiol 75:246–251

    Article  CAS  PubMed  Google Scholar 

  • Lemon KP, Higgins DE, Kolter R (2007) Flagellar motility is critical for Listeria monocytogenes biofilm formation. J Bacteriol 189:4418–4424

    Article  CAS  PubMed  Google Scholar 

  • Li C, Wong WH (2001) Model-based analysis of oligonucleotide arrays: model validation, design issues and standard error application. Genome Biol 2:1

    Google Scholar 

  • Lindberg U, Hanson LA, Jodal U, Lidin-Janson G, Lincoln K, Olling S (1975) Asymptomatic bacteriuria in schoolgirls. II. Differences in Escherichia coli causing asymptomatic bacteriuria. Acta Paediatr Scand 64:432–436

    Article  CAS  PubMed  Google Scholar 

  • Lloyd AL, Henderson TA, Vigil PD, Mobley HLT (2009) Genomic islands of uropathogenic Escherichia coli contribute to virulence. J Bacteriol 191:3469–3481

    Article  CAS  PubMed  Google Scholar 

  • Lodinova-Zadnikova R, Sonnenborn U (1997) Effect of preventive administration of a nonpathogenic Escherichia coli strain on the colonization of the intestine with microbial pathogens in newborn infants. Biol Neonate 71:224–232

    Article  CAS  PubMed  Google Scholar 

  • Lodinova-Zadnikova R, Bartakova Z, Tlaskalova H (1992) The effect of oral colonization by non-pathogenic E. coli on the immune response in neonates and possibilities of its use in the prevention of nosocomial infections in children at risk. Cesk Epidemiol Mikrobiol Imunol 42:126–132

    CAS  PubMed  Google Scholar 

  • Mabbett AN, Ulett GC, Watts RE, Tree JJ, Totsika M, Ong CL, Wood JM, Monaghan W, Looke DF, Nimmo GR, Svanborg C, Schembri MA (2009) Virulence properties of asymptomatic bacteriuria Escherichia coli. Int J Med Microbiol 299:53–63

    Article  CAS  PubMed  Google Scholar 

  • Macfarlane S, Dillon JF (2007) Microbial biofilms in the human gastrointestinal tract. J Appl Microbiol 102:1187–1196

    Article  CAS  PubMed  Google Scholar 

  • Merritt PM, Danhorn T, Fuqua C (2007) Motility and chemotaxis in Agrobacterium tumefaciens surface attachment and biofilm formation. J Bacteriol 189:8005–8014

    Article  CAS  PubMed  Google Scholar 

  • Mobley HLT, Green DM, Trifillis AL, Johnson DE, Chippendale GR, Lockatell CV, Jones BD, Warren JW (1990) Pyelonephritogenic Escherichia coli and killing of cultured human renal proximal tubular epithelial cells: role of hemolysin in some strains. Infect Immun 58:1281–1289

    CAS  PubMed  Google Scholar 

  • Neidhardt FC, Bloch PL, Smith DF (1974) Culture Medium for Enterobacteria. J Bacteriol 119:736–747

    CAS  PubMed  Google Scholar 

  • O’Toole GA, Kolter R (1998) Flagellar and twitching motility are necessary for Pseudomonas aeruginosa biofilm development. Mol Microbiol 30:295–304

    Article  PubMed  Google Scholar 

  • O’Toole G, Kaplan HB, Kolter R (2000) Biofilm formation as microbial development. Annu Rev Microbiol 54:49–79

    Article  PubMed  Google Scholar 

  • Oscarsson J, Mizunoe Y, Uhlin BE, Haydon DJ (1996) Induction of haemolytic activity in Escherichia coli by the slyA gene product. Mol Microbiol 20:191–199

    Article  CAS  PubMed  Google Scholar 

  • Ren D, Bedzyk LA, Thomas SM, Ye RW, Wood TK (2004) Gene expression in Escherichia coli biofilms. Appl Microbiol Biotechnol 64:515–524

    Article  CAS  PubMed  Google Scholar 

  • Roos V, Klemm P (2006) Global gene expression profiling of the asymptomatic bacteriuria Escherichia coli strain 83972 in the human urinary tract. Infect Immun 74:3565–3575

    Article  CAS  PubMed  Google Scholar 

  • Roos V, Schembri MA, Ulett GC, Klemm P (2006a) Asymptomatic bacteriuria Escherichia coli strain 83972 carries mutations in the foc locus and is unable to express F1C fimbriae. Microbiology 152:1799–1806

    Article  CAS  PubMed  Google Scholar 

  • Roos V, Ulett GC, Schembri MA, Klemm P (2006b) The asymptomatic bacteriuria Escherichia coli strain 83972 out-competes UPEC strains in human urine. Infect Immun 74:615–624

    Article  CAS  PubMed  Google Scholar 

  • Rudd KE, Ian H-S, Valerie CW, Amos B (1998) Low molecular weight proteins: a challenge for post-genomic research. Electrophoresis 19:536–544

    Article  CAS  PubMed  Google Scholar 

  • Russo TA, Carlino UB, Johnson JR (2001) Identification of a new iron-regulated virulence gene, ireA, in an extraintestinal pathogenic isolate of Escherichia coli. Infect Immun 69:6209–6216

    Article  CAS  PubMed  Google Scholar 

  • Schembri MA, Kjaergaard K, Klemm P (2003) Global gene expression in Escherichia coli biofilms. Mol Microbiol 48:253–267

    Article  CAS  PubMed  Google Scholar 

  • Schultz M (2008) Clinical use of E. coli Nissle 1917 in inflammatory bowel disease. Inflamm Bowel Dis 14:1012–1018

    Article  PubMed  Google Scholar 

  • Schulze J, Sonnenborn U (1995) Oral administration of a certain strain of live Escherichia coli for intestinal disorders? Infection 23:184–188

    Article  CAS  PubMed  Google Scholar 

  • Snyder JA, Haugen BJ, Buckles EL, Lockatell CV, Johnson DE, Donnenberg MS, Welch RA, Mobley HL (2004) Transcriptome of uropathogenic Escherichia coli during urinary tract infection. Infect Immun 72:6373–6381

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Sundén F, Håkansson L, Ljunggren E, Wullt B (2006) Bacterial interference–is deliberate colonization with Escherichia coli 83972 an alternative treatment for patients with recurrent urinary tract infection? Int J Antimicrob Agents 28S:S26–S29

    Article  Google Scholar 

  • Vejborg RM, Friis C, Hancock V, Schembri MA, Klemm P (2010) A virulent parent with probiotic progeny: comparative genomics of Escherichia coli strains CFT073, Nissle 1917 and ABU 83972. Mol Genet Genomics 283:469–484

    Article  CAS  PubMed  Google Scholar 

  • Warren JW (2001) Catheter-associated urinary tract infections. Int J Antimicrob Agents 17:299–303

    Article  CAS  PubMed  Google Scholar 

  • Weber MM, French CL, Barnes MB, Siegele DA, McLean RJ (2010) A previously uncharacterized gene, yjfO (bsmA) influences Escherichia coli biofilm formation and stress response. Microbiology 156:139–147

  • Welch RA, Burland V, Plunkett G 3rd, Redford P, Roesch P, Rasko D, Buckles EL, Liou SR, Boutin A, Hackett J, Stroud D, Mayhew GF, Rose DJ, Zhou S, Schwartz DC, Perna NT, Mobley HL, Donnenberg MS, Blattner FR (2002) Extensive mosaic structure revealed by the complete genome sequence of uropathogenic Escherichia coli. Proc Natl Acad Sci USA 99:17020–17024

    Article  CAS  PubMed  Google Scholar 

  • Wood TK (2009) Insights on Escherichia coli biofilm formation and inhibition from whole-transcriptome profiling. Environ Microbiol 11:1–15

    Article  CAS  PubMed  Google Scholar 

  • Wood TK, Gonzalez Barrios AF, Herzberg M, Lee J (2006) Motility influences biofilm architecture in Escherichia coli. Appl Microbiol Biotechnol 72:361–367

    Article  CAS  PubMed  Google Scholar 

  • Zdziarski J, Svanborg C, Wullt B, Hacker J, Dobrindt U (2007) Molecular basis of commensalism in the urinary tract: low virulence or virulence attenuation? Infect Immun 76:695–703

    Article  PubMed  Google Scholar 

  • Zhang XS, Garcia-Contreras R, Wood TK (2007) YcfR (BhsA) influences Escherichia coli biofilm formation through stress response and surface hydrophobicity. J Bacteriol 189:3051–3062

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We thank Birthe Jul Bondo for expert technical assistance. This work was supported by grants from Lundbeckfonden (R17-A1603) and FSS (271-06-0555).

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Correspondence to Viktoria Hancock.

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Communicated by D. Andersson.

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Hancock, V., Vejborg, R.M. & 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). https://doi.org/10.1007/s00438-010-0578-8

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