Capsular genotype and lipooligosaccharide locus class distribution in Campylobacter jejuni from young children with diarrhea and asymptomatic carriers in Bangladesh

  • Z. Islam
  • S. K. Sarker
  • I. Jahan
  • K. S. Farzana
  • D. Ahmed
  • A. S. G. Faruque
  • P. Guerry
  • F. Poly
  • A. P. Heikema
  • H. P. Endtz
Original Article


Campylobacter jejuni-related diarrheal diseases is one of the major health issues among young children (0–59 months old) in low-income countries. Monitoring of the capsular (capsule polysaccharide, CPS) types of virulent C. jejuni strains in regions where the disease is endemic is of great importance for the development of a customized capsule-based multivalent vaccine. Therefore, we aimed to determine the prevalence of CPS genotypes among C. jejuni strains isolated from young children with enteritis (n = 152) and asymptomatic carriers matched by age, sex, and residence defined as the control group (n = 215) in Bangladesh. CPS genotyping was performed using a newly established multiplex polymerase chain reaction (PCR) method and lipooligosaccharide (LOS) locus classes (A–E) were characterized using PCR as well. We identified 24 different CPS genotypes among the 367 isolates. Four prevalent capsular types, HS5/31 complex (n = 27, 18%), HS3 (n = 26, 17%), HS4A (n = 10, 7%), and HS8/17 (n = 10, 7%) covered almost 50% of the strains from enteritis patients and 43% of the isolates from controls. In combination, the CPS genotype and LOS class was not discriminative between cases and controls. Dominant capsular types previously identified in C. jejuni strains isolated from patients with Guillain–Barré syndrome in Bangladesh were rarely detected in strains isolated from the young children. A similar distribution was evident among enteritis- and control-related strains when comparison was done between CPS types and LOS classes. This is the first systematic study presenting the distribution of CPS genotypes of C. jejuni strains isolated in Bangladesh from children with diarrhea and controls, with capsular genotypes HS5/31 complex, HS3, HS4A, and HS8/17 being prevalent in both. In conclusion, systematic studies are required to develop a multivalent capsule-based vaccine for children in low-income countries.



This research study was funded by icddr,b's core donors through mentoring program. icddr,b also gratefully acknowledges the following donors who provide unrestricted support: the Government of the People's Republic of Bangladesh, Global Affairs Canada (GAC), Swedish International Development Cooperation Agency (Sida), and the Department for International Development (UK Aid).

Compliance with Ethical Standards

Conflict of Interest

The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors declare that they have no conflict of interest.


  1. 1.
    Allos BM (2001) Campylobacter jejuni infections: update on emerging issues and trends. Clin Infect Dis 32(8):1201–1206CrossRefPubMedGoogle Scholar
  2. 2.
    Butzler JP (2004) Campylobacter, from obscurity to celebrity. Clin Microbiol Infect 10(10):868–876CrossRefPubMedGoogle Scholar
  3. 3.
    Humphrey T, O’Brien S, Madsen M (2007) Campylobacters as zoonotic pathogens: a food production perspective. Int J Food Microbiol 117(3):237–257CrossRefPubMedGoogle Scholar
  4. 4.
    Mills DC, Gundogdu O, Elmi A et al (2012) Increase in Campylobacter jejuni invasion of intestinal epithelial cells under low-oxygen coculture conditions that reflect the in vivo environment. Infect Immun 80(5):1690–1698CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Ang CW, Jacobs BC, Laman JD (2004) The Guillain–Barré syndrome: a true case of molecular mimicry. Trends Immunol 25(2):61–66CrossRefPubMedGoogle Scholar
  6. 6.
    Pope JE, Krizova A, Garg AX, Thiessen-Philbrook H, Ouimet JM (2007) Campylobacter reactive arthritis: a systematic review. Semin Arthritis Rheum 37(1):48–55CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Thabane M, Simunovic M, Akhtar-Danesh N et al (2010) An outbreak of acute bacterial gastroenteritis is associated with an increased incidence of irritable bowel syndrome in children. Am J Gastroenterol 105(4):933–939CrossRefPubMedGoogle Scholar
  8. 8.
    Aspinall GD, McDonald AG, Pang H, Kurjanczyk LA, Penner JL (1993) An antigenic polysaccharide from Campylobacter coli serotype O:30. Structure of a teichoic acid-like antigenic polysaccharide associated with the lipopolysaccharide. J Biol Chem 268(24):18321–18329Google Scholar
  9. 9.
    Aspinall GO, Lynch CM, Pang H, Shaver RT, Moran AP (1995) Chemical structures of the core region of Campylobacter jejuni O:3 lipopolysaccharide and an associated polysaccharide. Eur J Biochem 231(3):570–578CrossRefPubMedGoogle Scholar
  10. 10.
    Parkhill J, Wren BW, Mungall K et al (2000) The genome sequence of the food-borne pathogen Campylobacter jejuni reveals hypervariable sequences. Nature 403(6770):665–668CrossRefPubMedGoogle Scholar
  11. 11.
    Bachtiar BM, Coloe PJ, Fry BN (2007) Knockout mutagenesis of the kpsE gene of Campylobacter jejuni 81116 and its involvement in bacterium–host interactions. FEMS Immunol Med Microbiol 49(1):149–154CrossRefPubMedGoogle Scholar
  12. 12.
    Bacon DJ, Szymanski CM, Burr DH, Silver RP, Alm RA, Guerry P (2001) A phase-variable capsule is involved in virulence of Campylobacter jejuni 81-176. Mol Microbiol 40(3):769–777CrossRefPubMedGoogle Scholar
  13. 13.
    Guerry P, Poly F, Riddle M, Maue AC, Chen YH, Monteiro MA (2012) Campylobacter polysaccharide capsules: virulence and vaccines. Front Cell Infect Microbiol 2:7CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Murray CJ, Vos T, Lozano R et al (2012) Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 380(9859):2197–2223CrossRefPubMedGoogle Scholar
  15. 15.
    Walker CLF, Perin J, Aryee MJ, Boschi-Pinto C, Black RE (2012) Diarrhea incidence in low- and middle-income countries in 1990 and 2010: a systematic review. BMC Public Health 12(1):220CrossRefGoogle Scholar
  16. 16.
    Lamberti LM, Fischer Walker CL, Noiman A, Victora C, Black RE (2011) Breastfeeding and the risk for diarrhea morbidity and mortality. BMC Public Health 11(Suppl 3):S15CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Maue AC, Poly F, Guerry P (2014) A capsule conjugate vaccine approach to prevent diarrheal disease caused by Campylobacter jejuni. Hum Vaccin Immunother 10(6):1499–1504CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Roberts IS (1996) The biochemistry and genetics of capsular polysaccharide production in bacteria. Annu Rev Microbiol 50(1):285–315CrossRefPubMedGoogle Scholar
  19. 19.
    Karlyshev AV, Champion OL, Churcher C et al (2005) Analysis of Campylobacter jejuni capsular loci reveals multiple mechanisms for the generation of structural diversity and the ability to form complex heptoses. Mol Microbiol 55(1):90–103CrossRefPubMedGoogle Scholar
  20. 20.
    Heikema AP, Islam Z, Horst-Kreft D et al (2015) Campylobacter jejuni capsular genotypes are related to Guillain–Barré syndrome. Clin Microbiol Infect 21(9):852.e1–852.e9CrossRefGoogle Scholar
  21. 21.
    Penner JL, Hennessy JN, Congi RV (1983) Serotyping of Campylobacter jejuni and Campylobacter coli on the basis of thermostable antigens. Eur J Clin Microbiol 2(4):378–383CrossRefPubMedGoogle Scholar
  22. 22.
    Pike BL, Guerry P, Poly F (2013) Global distribution of Campylobacter jejuni Penner serotypes: a systematic review. PLoS One 8(6):e67375CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Poly F, Serichatalergs O, Schulman M et al (2011) Discrimination of major capsular types of Campylobacter jejuni by multiplex PCR. J Clin Microbiol 49(5):1750–1757CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Kotloff KL, Blackwelder WC, Nasrin D et al (2012) The Global Enteric Multicenter Study (GEMS) of diarrheal disease in infants and young children in developing countries: epidemiologic and clinical methods of the case/control study. Clin Infect Dis 55(Suppl 4):S232–S245CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Kotloff KL, Nataro JP, Blackwelder WC et al (2013) Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case–control study. Lancet 382(9888):209–222CrossRefPubMedGoogle Scholar
  26. 26.
    Levine MM, Kotloff KL, Nataro JP, Muhsen K (2012) The Global Enteric Multicenter Study (GEMS): impetus, rationale, and genesis. Clin Infect Dis 55(Suppl 4):S215–S224CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Bertolo L, Ewing CP, Maue A, Poly F, Guerry P, Monteiro MA (2013) The design of a capsule polysaccharide conjugate vaccine against Campylobacter jejuni serotype HS15. Carbohydr Res 366:45–49CrossRefPubMedGoogle Scholar
  28. 28.
    Talukder KA, Aslam M, Islam Z et al (2008) Prevalence of virulence genes and cytolethal distending toxin production in Campylobacter jejuni isolates from diarrheal patients in Bangladesh. J Clin Microbiol 46(4):1485–1488CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Godschalk PC, Heikema AP, Gilbert M et al (2004) The crucial role of Campylobacter jejuni genes in anti-ganglioside antibody induction in Guillain–Barre syndrome. J Clin Invest 114(11):1659–1665CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Parker CT, Horn ST, Gilbert M, Miller WG, Woodward DL, Mandrell RE (2005) Comparison of Campylobacter jejuni lipooligosaccharide biosynthesis loci from a variety of sources. J Clin Microbiol 43(6):2771–2781CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Chandra Mouli Natchu U, Bhatnagar S (2013) Diarrhoea in children: identifying the cause and burden. Lancet 382(9888):184–186CrossRefGoogle Scholar
  32. 32.
    Islam Z, van Belkum A, Cody AJ et al (2009) Campylobacter jejuni HS:23 and Guillain–Barre syndrome, Bangladesh. Emerg Infect Dis 15(8):1315–1317CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Kuroki S, Saida T, Nukina M et al (1993) Campylobacter jejuni strains from patients with Guillain–Barré syndrome belong mostly to Penner serogroup 19 and contain beta-N-acetylglucosamine residues. Ann Neurol 33(3):243–247CrossRefPubMedGoogle Scholar
  34. 34.
    Lastovica AJ, Goddard EA, Argent AC (1997) Guillain–Barré syndrome in South Africa associated with Campylobacter jejuni O:41 strains. J Infect Dis 176(Suppl 2):S139–S143CrossRefPubMedGoogle Scholar
  35. 35.
    Endtz HP, Ang CW, van Den Braak N et al (2000) Molecular characterization of Campylobacter jejuni from patients with Guillain–Barré and Miller Fisher syndromes. J Clin Microbiol 38(6):2297–2301PubMedPubMedCentralGoogle Scholar
  36. 36.
    Nachamkin I, Engberg J, Gutacker M et al (2001) Molecular population genetic analysis of Campylobacter jejuni HS:19 associated with Guillain–Barré syndrome and gastroenteritis. J Infect Dis 184(2):221–226CrossRefPubMedGoogle Scholar
  37. 37.
    Rees JH, Soudain SE, Gregson NA, Hughes RA (1995) Campylobacter jejuni infection and Guillain–Barré syndrome. N Engl J Med 333(21):1374–1379CrossRefPubMedGoogle Scholar
  38. 38.
    Jacobs BC, Endtz H, van der Meché FG, Hazenberg MP, Achtereekte HA, van Doorn PA (1995) Serum anti-GQ1b IgG antibodies recognize surface epitopes on Campylobacter jejuni from patients with Miller Fisher syndrome. Ann Neurol 37(2):260–264CrossRefPubMedGoogle Scholar
  39. 39.
    Yuki N (1997) Molecular mimicry between gangliosides and lipopolysaccharides of Campylobacter jejuni isolated from patients with Guillain–Barré syndrome and Miller Fisher syndrome. J Infect Dis 176(Suppl 2):S150–S153CrossRefPubMedGoogle Scholar
  40. 40.
    Sheikh KA, Ho TW, Nachamkin I et al (1998) Molecular mimicry in Guillain–Barré syndrome. Ann N Y Acad Sci 845:307–321CrossRefPubMedGoogle Scholar
  41. 41.
    Godschalk PC, Heikema AP, Gilbert M et al (2004) The crucial role of Campylobacter jejuni genes in anti-ganglioside antibody induction in Guillain–Barré syndrome. J Clin Invest 114(11):1659–1665CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  • Z. Islam
    • 1
  • S. K. Sarker
    • 1
  • I. Jahan
    • 1
  • K. S. Farzana
    • 1
  • D. Ahmed
    • 1
  • A. S. G. Faruque
    • 2
  • P. Guerry
    • 3
  • F. Poly
    • 3
  • A. P. Heikema
    • 4
  • H. P. Endtz
    • 1
    • 4
    • 5
  1. 1.Laboratory Sciences and Services DivisionInternational Centre for Diarrhoeal Disease Research (icddr,b)DhakaBangladesh
  2. 2.Nutrition and Clinical Services DivisionInternational Centre for Diarrhoeal Disease Research, (icddr,b)DhakaBangladesh
  3. 3.Naval Medical Research CenterSilver SpringUSA
  4. 4.Department of Medical Microbiology and Infectious DiseasesErasmus MC, University Medical Centre RotterdamRotterdamThe Netherlands
  5. 5.Fondation MérieuxLyonFrance

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