Medical Microbiology and Immunology

, Volume 204, Issue 6, pp 681–692 | Cite as

Prevalence of Mycobacterium avium subsp. paratuberculosis and Escherichia coli in blood samples from patients with inflammatory bowel disease

  • Nair Nazareth
  • Fernando Magro
  • Elisabete Machado
  • Teresa Gonçalves Ribeiro
  • António Martinho
  • Pedro Rodrigues
  • Rita Alves
  • Gonçalo Nuno Macedo
  • Daniela Gracio
  • Rosa Coelho
  • Candida Abreu
  • Rui Appelberg
  • Camila Dias
  • Guilherme Macedo
  • Tim Bull
  • Amélia Sarmento
Original Investigation


Mycobacterium avium subsp. paratuberculosis (MAP) and adherent-invasive Escherichia coli (AIEC) have been implicated as primary triggers in Crohn’s disease (CD). In this study, we evaluated the prevalence of MAP and E. coli (EC) DNA in peripheral blood from 202 inflammatory bowel disease (IBD) patients at various disease periods and compared against 24 cirrhotic patients with ascites (CIR) (non-IBD controls) and 29 healthy controls (HC). MAP DNA was detected by IS900-specific nested PCR, EC DNA by malB-specific nested PCR and AIEC identity, in selected samples, by sequencing of fimH gene. CD patients with active disease showed the highest MAP DNA prevalence among IBD patients (68 %). Infliximab treatment resulted in decreased MAP detection. CIR patients had high individual and coinfection rates (75 % MAP, 88 % EC and 67 % MAP and EC), whilst HC controls had lower MAP prevalence (38 %) and EC was undetectable in this control group. EC DNA prevalence in IBD patients was highly associated with CD, and 80 % of EC from the selected samples of CD patients analyzed carried the fimH30 allele, with a mutation strongly associated with AIEC. Our results show that coinfection with MAP and AIEC is common and persistent in CD, although the high MAP and EC detection in CIR patients suggested that colonization is, at least, partially dependent on increased gut permeability. Nevertheless, facilitative mechanisms between a susceptible host and these two potential human pathogens may allow their implication in CD pathogenesis.


Inflammatory bowel disease Mycobacterium avium subsp. paratuberculosis (MAP) Adherent-invasive Escherichia coli (AIEC) IS900, fimH gene 



This work received financial support from the European Union (FEDER funds), through Programa Operacional Factores de Competitividade—COMPETE, and from National Funds (FCT, Fundação para a Ciência e a Tecnologia), through grant number PIC/IC/82802/2007. The authors wish to thank all patients and controls for their participation in this study.

Conflict of interest

The authors declare that they have no competing interests.


  1. 1.
    Xavier RJ, Podolsky DK (2007) Unravelling the pathogenesis of inflammatory bowel disease. Nature 448(7152):427–434. doi: 10.1038/nature06005 CrossRefPubMedGoogle Scholar
  2. 2.
    Sartor RB (2008) Microbial influences in inflammatory bowel diseases. Gastroenterology 134(2):577–594. doi: 10.1053/j.gastro.2007.11.059 CrossRefPubMedGoogle Scholar
  3. 3.
    Kleessen B, Kroesen AJ, Buhr HJ, Blaut M (2002) Mucosal and invading bacteria in patients with inflammatory bowel disease compared with controls. Scand J Gastroenterol 37(9):1034–1041CrossRefPubMedGoogle Scholar
  4. 4.
    Eckburg PB, Relman DA (2007) The role of microbes in Crohn’s disease. Clin Infect Dis 44(2):256–262. doi: 10.1086/510385 CrossRefPubMedGoogle Scholar
  5. 5.
    De Hertogh G, Aerssens J, Geboes KP, Geboes K (2008) Evidence for the involvement of infectious agents in the pathogenesis of Crohn’s disease. World J Gastroenterol WJG 14(6):845–852CrossRefPubMedGoogle Scholar
  6. 6.
    Pickup RW, Rhodes G, Arnott S, Sidi-Boumedine K, Bull TJ, Weightman A, Hurley M, Hermon-Taylor J (2005) Mycobacterium avium subsp. paratuberculosis in the catchment area and water of the River Taff in South Wales, United Kingdom, and its potential relationship to clustering of Crohn’s disease cases in the city of Cardiff. Appl Environ Microbiol 71(4):2130–2139. doi: 10.1128/AEM.71.4.2130-2139.2005 PubMedCentralCrossRefPubMedGoogle Scholar
  7. 7.
    Rhodes G, Henrys P, Thomson BC, Pickup RW (2013) Mycobacterium avium subspecies paratuberculosis is widely distributed in British soils and waters: implications for animal and human health. Environ Microbiol 15(10):2761–2774. doi: 10.1111/1462-2920.12137 PubMedGoogle Scholar
  8. 8.
    Cosma CL, Sherman DR, Ramakrishnan L (2003) The secret lives of the pathogenic mycobacteria. Ann Rev Microbiol 57:641–676. doi: 10.1146/annurev.micro.57.030502.091033 CrossRefGoogle Scholar
  9. 9.
    Orme IM, Ordway DJ (2014) The host response to non-tuberculous mycobacterial infections of current clinical importance. Infect Immun 82(9):3516–3522. doi: 10.1128/IAI.01606-13 PubMedCentralCrossRefPubMedGoogle Scholar
  10. 10.
    Glawischnig W, Steineck T, Spergser J (2006) Infections caused by Mycobacterium avium subspecies avium, hominissuis, and paratuberculosis in free-ranging red deer (Cervus elaphus hippelaphus) in Austria, 2001–2004. J Wildl Dis 42(4):724–731. doi: 10.7589/0090-3558-42.4.724 CrossRefPubMedGoogle Scholar
  11. 11.
    Judge J, Kyriazakis I, Greig A, Allcroft DJ, Hutchings MR (2005) Clustering of Mycobacterium avium subsp. paratuberculosis in rabbits and the environment: How hot is a hot spot? Appl Environ Microbiol 71(10):6033–6038. doi: 10.1128/AEM.71.10.6033-6038.2005 PubMedCentralCrossRefPubMedGoogle Scholar
  12. 12.
    McClure HM, Chiodini RJ, Anderson DC, Swenson RB, Thayer WR, Coutu JA (1987) Mycobacterium paratuberculosis infection in a colony of stumptail macaques (Macaca arctoides). J Infect Dis 155(5):1011–1019CrossRefPubMedGoogle Scholar
  13. 13.
    Chiodini RJ, Van Kruiningen HJ, Thayer WR, Merkal RS, Coutu JA (1984) Possible role of mycobacteria in inflammatory bowel disease. I. An unclassified Mycobacterium species isolated from patients with Crohn’s disease. Dig Dis Sci 29(12):1073–1079CrossRefPubMedGoogle Scholar
  14. 14.
    Behr MA, Kapur V (2008) The evidence for Mycobacterium paratuberculosis in Crohn’s disease. Curr Opin Gastroenterol 24(1):17–21. doi: 10.1097/MOG.0b013e3282f1dcc4 CrossRefPubMedGoogle Scholar
  15. 15.
    Chacon O, Bermudez LE, Barletta RG (2004) Johne’s disease, inflammatory bowel disease, and Mycobacterium paratuberculosis. Annu Rev Microbiol 58:329–363CrossRefPubMedGoogle Scholar
  16. 16.
    Abubakar I, Myhill D, Aliyu SH, Hunter PR (2008) Detection of Mycobacterium avium subspecies paratuberculosis from patients with Crohn’s disease using nucleic acid-based techniques: a systematic review and meta-analysis. Inflamm Bowel Dis 14(3):401–410. doi: 10.1002/ibd.20276 CrossRefPubMedGoogle Scholar
  17. 17.
    Feller M, Huwiler K, Stephan R, Altpeter E, Shang A, Furrer H, Pfyffer GE, Jemmi T, Baumgartner A, Egger M (2007) Mycobacterium avium subspecies paratuberculosis and Crohn’s disease: a systematic review and meta-analysis. Lancet Infect Dis 7(9):607–613. doi: 10.1016/S1473-3099(07)70211-6 CrossRefPubMedGoogle Scholar
  18. 18.
    Naser SA, Collins MT, Crawford JT, Valentine JF (2009) Culture of Mycobacterium avium subspecies paratuberculosis (MAP) from the blood of patients with Crohn’s disease: a follow-up blind multi center investigation. Open Inflamm J 2:22–23CrossRefGoogle Scholar
  19. 19.
    Bull TJ, McMinn EJ, Sidi-Boumedine K, Skull A, Durkin D, Neild P, Rhodes G, Pickup R, Hermon-Taylor J (2003) Detection and verification of Mycobacterium avium subsp. paratuberculosis in fresh ileocolonic mucosal biopsy specimens from individuals with and without Crohn’s disease. J Clin Microbiol 41(7):2915–2923PubMedCentralCrossRefPubMedGoogle Scholar
  20. 20.
    Lee A, Griffiths TA, Parab RS, King RK, Dubinsky MC, Urbanski SJ, Wrobel I, Rioux KP (2011) Association of Mycobacterium avium subspecies paratuberculosis with Crohn disease in pediatric patients. J Pediatr Gastroenterol Nutr 52(2):170–174. doi: 10.1097/MPG.0b013e3181ef37ba CrossRefPubMedGoogle Scholar
  21. 21.
    Wynne JW, Bull TJ, Seemann T, Bulach DM, Wagner J, Kirkwood CD, Michalski WP (2011) Exploring the zoonotic potential of Mycobacterium avium subspecies paratuberculosis through comparative genomics. PLoS One 6(7):e22171. doi: 10.1371/journal.pone.0022171.t004 PubMedCentralCrossRefPubMedGoogle Scholar
  22. 22.
    Juste RA, Elguezabal N, Garrido JM, Pavon A, Geijo MV, Sevilla I, Cabriada J-L, Tejada A, García-Campos F, Casado R, Ochotorena I, Izeta A, Greenstein RJ, Romesberg F (2008) On the prevalence of M. avium subspecies paratuberculosis DNA in the blood of healthy individuals and patients with inflammatory bowel disease. PLoS One 3(7):e2537. doi: 10.1371/journal.pone.0002537 PubMedCentralCrossRefPubMedGoogle Scholar
  23. 23.
    Ricanek P, Lothe SM, Szpinda I, Jorde AT, Brackmann S, Perminow G, Jørgensen KK, Rydning A, Vatn MH, Tønjum T, group IIs (2010) Paucity of mycobacteria in mucosal bowel biopsies from adults and children with early inflammatory bowel disease. J Crohns Colitis 4(5):561–566. doi: 10.1016/j.crohns.2010.05.003 CrossRefPubMedGoogle Scholar
  24. 24.
    Darfeuille-Michaud A, Boudeau J, Bulois P, Neut C, Glasser AL, Barnich N, Bringer MA, Swidsinski A, Beaugerie L, Colombel JF (2004) High prevalence of adherent-invasive Escherichia coli associated with ileal mucosa in Crohn’s disease. Gastroenterology 127(2):412–421CrossRefPubMedGoogle Scholar
  25. 25.
    Sepehri S, Kotlowski R, Bernstein CN, Krause DO (2009) Phylogenetic analysis of inflammatory bowel disease associated Escherichia coli and the fimH virulence determinant. Inflamm Bowel Dis 15(11):1737–1745. doi: 10.1002/ibd.20966 CrossRefPubMedGoogle Scholar
  26. 26.
    Flores J, Okhuysen PC (2009) Enteroaggregative Escherichia coli infection. Curr Opin Gastroenterol 25(1):8–11. doi: 10.1097/MOG.0b013e32831dac5e CrossRefPubMedGoogle Scholar
  27. 27.
    Darfeuille-Michaud A, Neut C, Barnich N, Lederman E, Di Martino P, Desreumaux P, Gambiez L, Joly B, Cortot A, Colombel JF (1998) Presence of adherent Escherichia coli strains in ileal mucosa of patients with Crohn’s disease. Gastroenterology 115(6):1405–1413CrossRefPubMedGoogle Scholar
  28. 28.
    Lapaquette P, Glasser AL, Huett A, Xavier RJ, Darfeuille-Michaud A (2010) Crohn’s disease-associated adherent-invasive E. coli are selectively favoured by impaired autophagy to replicate intracellularly. Cell Microbiol 12(1):99–113. doi: 10.1111/j.1462-5822.2009.01381.x PubMedCentralCrossRefPubMedGoogle Scholar
  29. 29.
    Strober W (2011) Adherent-invasive E. coli in Crohn disease: bacterial “agent provocateur”. J Clin Investig 121(3):841–844. doi: 10.1172/JCI46333 PubMedCentralCrossRefPubMedGoogle Scholar
  30. 30.
    Vejborg RM, Hancock V, Petersen AM, Krogfelt KA, Klemm P (2011) Comparative genomics of Escherichia coli isolated from patients with inflammatory bowel disease. BMC Genom 12:316–328. doi: 10.1186/1471-2164-12-316 CrossRefGoogle Scholar
  31. 31.
    Martinez-Medina M, Aldeguer X, Lopez-Siles M, Gonzalez-Huix F, Lopez-Oliu C, Dahbi G, Blanco JE, Blanco J, Garcia-Gil LJ, Darfeuille-Michaud A (2009) Molecular diversity of Escherichia coli in the human gut: new ecological evidence supporting the role of adherent-invasive E. coli (AIEC) in Crohn’s disease. Inflamm Bowel Dis 15(6):872–882. doi: 10.1002/ibd.20860 CrossRefPubMedGoogle Scholar
  32. 32.
    Krause DO, Little AC, Dowd SE, Bernstein CN (2010) Complete genome sequence of adherent invasive Escherichia coli UM146 isolated from ileal Crohn’s disease biopsy tissue. J Bacteriol 193(2):583. doi: 10.1128/JB.01290-10 PubMedCentralCrossRefPubMedGoogle Scholar
  33. 33.
    Glasser AL, Boudeau J, Barnich N, Perruchot MH, Colombel JF, Darfeuille-Michaud A (2001) Adherent invasive Escherichia coli strains from patients with Crohn’s disease survive and replicate within macrophages without inducing host cell death. Infect Immun 69(9):5529–5537PubMedCentralCrossRefPubMedGoogle Scholar
  34. 34.
    Martinez-Medina M, Mora A, Blanco M, Lopez C, Alonso MP, Bonacorsi S, Nicolas-Chanoine MH, Darfeuille-Michaud A, Garcia-Gil J, Blanco J (2009) Similarity and divergence among adherent-invasive Escherichia coli and extraintestinal pathogenic E. coli strains. J Clin Microbiol 47(12):3968–3979. doi: 10.1128/JCM.01484-09 PubMedCentralCrossRefPubMedGoogle Scholar
  35. 35.
    Smith EJ, Thompson AP, O’Driscoll A, Clarke DJ (2013) Pathogenesis of adherent-invasive Escherichia coli. Future Microbiol 8(10):1289–1300. doi: 10.2217/fmb.13.94 CrossRefPubMedGoogle Scholar
  36. 36.
    Boudeau J, Glasser AL, Masseret E, Joly B, Darfeuille-Michaud A (1999) Invasive ability of an Escherichia coli strain isolated from the ileal mucosa of a patient with Crohn’s disease. Infect Immun 67(9):4499–4509PubMedCentralPubMedGoogle Scholar
  37. 37.
    Rolhion N, Darfeuille-Michaud A (2007) Adherent-invasive Escherichia coli in inflammatory bowel disease. Inflamm Bowel Dis 13(10):1277–1283. doi: 10.1002/ibd.20176 CrossRefPubMedGoogle Scholar
  38. 38.
    Boudeau J, Barnich N, Darfeuille-Michaud A (2001) Type 1 pili-mediated adherence of Escherichia coli strain LF82 isolated from Crohn’s disease is involved in bacterial invasion of intestinal epithelial cells. Mol Microbiol 39(5):1272–1284CrossRefPubMedGoogle Scholar
  39. 39.
    Barnich N, Carvalho FA, Glasser AL, Darcha C, Jantscheff P, Allez M, Peeters H, Bommelaer G, Desreumaux P, Colombel JF, Darfeuille-Michaud A (2007) CEACAM6 acts as a receptor for adherent-invasive E. coli, supporting ileal mucosa colonization in Crohn disease. J Clin Investig 117(6):1566–1574. doi: 10.1172/JCI30504 PubMedCentralCrossRefPubMedGoogle Scholar
  40. 40.
    Dreux N, Denizot J, Martinez-Medina M, Mellmann A, Billig M, Kisiela D, Chattopadhyay S, Sokurenko E, Neut C, Gower-Rousseau C, Colombel JF, Bonnet R, Darfeuille-Michaud A, Barnich N (2013) Point mutations in FimH adhesin of Crohn’s disease-associated adherent-invasive Escherichia coli enhance intestinal inflammatory response. PLoS Pathog 9(1):e1003141. doi: 10.1371/journal.ppat.1003141.s003 PubMedCentralCrossRefPubMedGoogle Scholar
  41. 41.
    Wine E, Ossa JC, Gray-Owen SD, Sherman PM (2010) Adherent-invasive Escherichia coli target the epithelial barrier. Gut Microbes 1(2):80–84. doi: 10.4161/gmic.1.2.11142 PubMedCentralCrossRefPubMedGoogle Scholar
  42. 42.
    Glasser AL, Darfeuille-Michaud A (2008) Abnormalities in the handling of intracellular bacteria in Crohn’s disease: a link between infectious etiology and host genetic susceptibility. Arch Immunol Ther Exp 56(4):237–244. doi: 10.1007/s00005-008-0026-1 CrossRefGoogle Scholar
  43. 43.
    Naser SA, Ghobrial G, Romero C, Valentine JF (2004) Culture of Mycobacterium avium subspecies paratuberculosis from the blood of patients with Crohn’s disease. Lancet 364(9439):1039–1044CrossRefPubMedGoogle Scholar
  44. 44.
    Golan L, Livneh-Kol A, Gonen E, Yagel S, Rosenshine I, Shpigel NY (2009) Mycobacterium avium paratuberculosis invades human small-intestinal goblet cells and elicits inflammation. J Infect Dis 199(3):350–354. doi: 10.1086/596033 CrossRefPubMedGoogle Scholar
  45. 45.
    Secott TE, Lin TL, Wu CC (2004) Mycobacterium avium subsp. paratuberculosis fibronectin attachment protein facilitates m-cell targeting and invasion through a fibronectin bridge with host integrins. Infect Immun 72(7):3724–3732. doi: 10.1128/IAI.72.7.3724-3732.2004 PubMedCentralCrossRefPubMedGoogle Scholar
  46. 46.
    Raso T, Crivellaro S, Chirillo MG, Pais P, Gaia E, Savoia D (2011) Analysis of Escherichia coli isolated from patients affected by Crohn’s disease. Curr Microbiol 63(2):131–137. doi: 10.1007/s00284-011-9947-8 CrossRefPubMedGoogle Scholar
  47. 47.
    Abendaño N, Juste RA, Alonso-Hearn M (2013) Anti-inflammatory and antiapoptotic responses to infection: a common denominator of human and bovine macrophages infected with Mycobacterium avium subsp. paratuberculosis. BioMed Res Int 2:1–7. doi: 10.1128/IAI.69.2.1002-1008.2001 CrossRefGoogle Scholar
  48. 48.
    Keown DA, Collings DA, Keenan JI (2012) Uptake and persistence of Mycobacterium avium subsp. paratuberculosis in human monocytes. Infect Immun 80(11):3768–3775. doi: 10.1128/IAI.00534-12 PubMedCentralCrossRefPubMedGoogle Scholar
  49. 49.
    Harvey RF, Bradshaw MJ (1980) Measuring Crohn’s disease activity. Lancet 1(8178):1134–1135CrossRefPubMedGoogle Scholar
  50. 50.
    Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, Travers S, Rachmilewitz D, Hanauer SB, Lichtenstein GR, de Villiers WJS, Present D, Sands BE, Colombel JF (2005) Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med 353(23):2462–2476. doi: 10.1056/NEJMoa050516 CrossRefPubMedGoogle Scholar
  51. 51.
    Suenaert P, Bulteel V, Lemmens L, Noman M, Geypens B, Van Assche G, Geboes K, Ceuppens JL, Rutgeerts P (2002) Anti-tumor necrosis factor treatment restores the gut barrier in Crohn’s disease. Am J Gastroenterol 97(8):2000–2004. doi: 10.1111/j.1572-0241.2002.05914.x CrossRefPubMedGoogle Scholar
  52. 52.
    Suenaert P, Bulteel V, Vermeire S, Noman M, Van Assche G, Rutgeerts P (2005) Hyperresponsiveness of the mucosal barrier in Crohn’s disease is not tumor necrosis factor-dependent. Inflamm Bowel Dis 11(7):667–673CrossRefPubMedGoogle Scholar
  53. 53.
    Dignass A, Van Assche G, Lindsay JO, Lemann M, Soderholm J, Colombel JF, Danese S, D’Hoore A, Gassull M, Gomollon F, Hommes DW, Michetti P, O’Morain C, Oresland T, Windsor A, Stange EF, Travis SP, Cs European, Colitis O (2010) The second European evidence-based consensus on the diagnosis and management of Crohn’s disease: current management. J Crohn’s Colitis 4(1):28–62. doi: 10.1016/j.crohns.2009.12.002 CrossRefGoogle Scholar
  54. 54.
    Dignass A, Eliakim R, Magro F, Maaser C, Chowers Y, Geboes K, Mantzaris G, Reinisch W, Colombel JF, Vermeire S, Travis S, Lindsay JO, Van Assche G (2012) Second European evidence-based consensus on the diagnosis and management of ulcerative colitis part 1: definitions and diagnosis. J Crohn’s Colitis 6(10):965–990Google Scholar
  55. 55.
    Sechi LA, Scanu AM, Molicotti P, Cannas S, Mura M, Dettori G, Fadda G, Zanetti S (2005) Detection and isolation of Mycobacterium avium subspecies paratuberculosis from intestinal mucosal biopsies of patients with and without Crohn’s disease in Sardinia. Am J Gastroenterol 100(7):1529–1536. doi: 10.1111/ajg.2005.100.issue-7 CrossRefPubMedGoogle Scholar
  56. 56.
    Singh A (2008) Presence and characterization of Mycobacterium avium subspecies paratuberculosis from clinical and suspected cases of Crohn’s disease and in the healthy human population in India. Int J Infect Dis 12(2):190–197. doi: 10.1016/j.ijid.2007.06.008 CrossRefPubMedGoogle Scholar
  57. 57.
    Collins MT, Lisby G, Moser C, Chicks D, Christensen S, Reichelderfer M, Høiby N, Harms BA, Thomsen OO, Skibsted U, Binder V (2000) Results of multiple diagnostic tests for Mycobacterium avium subsp. paratuberculosis in patients with inflammatory bowel disease and in controls. J Clin Microbiol 38(12):4373–4381PubMedCentralPubMedGoogle Scholar
  58. 58.
    Tuci A, Tonon F, Castellani L, Sartini A, Roda G, Marocchi M, Caponi A, Munarini A, Rosati G, Ugolini G, Fuccio L, Scagliarini M, Bazzoli F, Belluzzi A (2011) Fecal detection of Mycobacterium avium paratuberculosis using the IS900 DNA sequence in Crohn’s disease and ulcerative colitis patients and healthy subjects. Dig Dis Sci 56(10):2957–2962. doi: 10.1007/s10620-011-1699-6 CrossRefPubMedGoogle Scholar
  59. 59.
    Darfeuille-Michaud A, Boudeau J, Bulois P, Neut C, Glasser A-L, Barnich N, Bringer M-A, Swidsinski A, Beaugerie L, Colombel JF (2004) High prevalence of adherent-invasive Escherichia coli associated with ileal mucosa in Crohn’s disease. Gastroenterology 127(2):412–421CrossRefPubMedGoogle Scholar
  60. 60.
    Corti S, Stephan R (2002) Detection of Mycobacterium avium subspecies paratuberculosis specific IS900 insertion sequences in bulk-tank milk samples obtained from different regions throughout Switzerland. BMC Microbiol 2:15PubMedCentralCrossRefPubMedGoogle Scholar
  61. 61.
    Tuci A, Tonon F, Castellani L, Sartini A, Roda G, Marocchi M, Caponi A, Munarini A, Rosati G, Ugolini G, Fuccio L, Scagliarini M, Bazzoli F, Belluzzi A (2011) Fecal detection of Mycobacterium avium paratuberculosis using the IS900 DNA sequence in Crohn’s disease and ulcerative colitis patients and healthy subjects. Dig Dis Sci 56(10):2957–2962. doi: 10.1007/s10620-011-1699-6 CrossRefPubMedGoogle Scholar
  62. 62.
    Hofnung M, Hatfield D, Schwartz M (1974) malB region in Escherichia coli K-12: characterization of new mutations. J Bacteriol 117(1):40–47PubMedCentralPubMedGoogle Scholar
  63. 63.
    Iebba V, Conte MP, Lepanto MS, Di Nardo G, Santangelo F, Aloi M, Totino V, Checchi MP, Longhi C, Cucchiara S, Schippa S (2012) Microevolution in fimH gene of mucosa-associated Escherichia coli strains isolated from pediatric patients with inflammatory bowel disease. Infect Immun 80(4):1408–1417. doi: 10.1128/IAI.06181-11 PubMedCentralCrossRefPubMedGoogle Scholar
  64. 64.
    Weissman SJ, Johnson JR, Tchesnokova V, Billig M, Dykhuizen D, Riddell K, Rogers P, Qin X, Butler-Wu S, Cookson BT, Fang FC, Scholes D, Chattopadhyay S, Sokurenko E (2012) High-resolution two-locus clonal typing of extraintestinal pathogenic Escherichia coli. Appl Environ Microbiol 78(5):1353–1360. doi: 10.1128/AEM.06663-11 PubMedCentralCrossRefPubMedGoogle Scholar
  65. 65.
    Giufre M, Accogli M, Farina C, Giammanco A, Pecile P, Cerquetti M (2014) Predominance of the fimH30 subclone among multidrug-resistant Escherichia coli strains belonging to sequence type 131 in Italy. J Infect Dis 209(4):629–630. doi: 10.1093/infdis/jit583 CrossRefPubMedGoogle Scholar
  66. 66.
    Chen Y, Yang F, Lu H, Wang B, Chen Y, Lei D, Wang Y, Zhu B, Li L (2011) Characterization of fecal microbial communities in patients with liver cirrhosis. Hepatology 54(2):562–572. doi: 10.1002/hep.24423 CrossRefPubMedGoogle Scholar
  67. 67.
    Such J, Frances R, Munoz C, Zapater P, Casellas JA, Cifuentes A, Rodriguez-Valera F, Pascual S, Sola-Vera J, Carnicer F, Uceda F, Palazon JM, Perez-Mateo M (2002) Detection and identification of bacterial DNA in patients with cirrhosis and culture-negative, nonneutrocytic ascites. Hepatology 36(1):135–141. doi: 10.1053/jhep.2002.33715 CrossRefPubMedGoogle Scholar
  68. 68.
    Nazareth N, Magro F, Appelberg R, Silva J, Gracio D, Coelho R, Cabral JM, Abreu C, Macedo G, Bull TJ, Sarmento A (2015) Increased viability but decreased culturability of Mycobacterium avium subsp. paratuberculosis in macrophages from inflammatory bowel disease patients under Infliximab treatment. Med Microbiol Immunol. doi: 10.1007/s00430-015-0393-2 Google Scholar
  69. 69.
    Wang RF, Cao WW, Cerniglia CE (1996) PCR detection and quantitation of predominant anaerobic bacteria in human and animal fecal samples. Appl Environ Microbiol 62(4):1242–1247PubMedCentralPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Nair Nazareth
    • 1
  • Fernando Magro
    • 2
    • 3
    • 4
  • Elisabete Machado
    • 1
    • 5
  • Teresa Gonçalves Ribeiro
    • 1
    • 5
  • António Martinho
    • 1
  • Pedro Rodrigues
    • 1
    • 6
  • Rita Alves
    • 1
  • Gonçalo Nuno Macedo
    • 1
  • Daniela Gracio
    • 2
    • 4
  • Rosa Coelho
    • 3
  • Candida Abreu
    • 7
    • 8
  • Rui Appelberg
    • 6
  • Camila Dias
    • 9
  • Guilherme Macedo
    • 3
  • Tim Bull
    • 10
  • Amélia Sarmento
    • 1
    • 6
  1. 1.FP-ENAS (UFP Energy, Environment and Health Research Unit), CEBIMED (Biomedical Research Centre)University Fernando PessoaPortoPortugal
  2. 2.Institute of Pharmacology and Therapeutics, Faculdade de MedicinaUniversidade do PortoPortoPortugal
  3. 3.Gastroenterology DepartmentCentro Hospitalar São JoãoPortoPortugal
  4. 4.MedInUP -Center for Drug Discovery and Innovative MedicinesUniversidade do PortoPortoPortugal
  5. 5.REQUIMTE, Laboratory of Microbiology, Faculdade de FarmáciaUniversidade do PortoPortoPortugal
  6. 6.Infection and Immunity Unit, IBMC – Instituto de Biologia Molecular e CelularUniversidade do PortoPortoPortugal
  7. 7.Department of Infectious DiseasesCentro Hospitalar S. JoãoPortoPortugal
  8. 8.Nephrology Research and Development UnitFaculdade de Medicina da Universidade do PortoPortoPortugal
  9. 9.Department of Biostatistics and Medical Informatics, Faculdade de MedicinaUniversidade do PortoPortoPortugal
  10. 10.Institute for Infection and ImmunitySt George’s University of LondonLondonUK

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