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Title: Distinct Campylobacter jejuni capsular types are related to Guillain-Barré syndrome in The Netherlands and Bangladesh

Author
item HEIKEMA, ASTRID - Erasmus Medical Center
item ISLAM, ZHAHIRUL - International Centre For Diarrhoeal Disease Research
item HORST-KREFT, DEBORAH - Erasmus Medical Center
item HUIZINGA, RUTH - Erasmus Medical Center
item JACOBS, BART - Erasmus Medical Center
item WAGENAAR, JAAP - Utrecht University
item POLY, FREDERIC - Us Naval Medical Research Center
item GUERRY, PATRICK - Us Naval Medical Research Center
item VAN BELKAM, ALEX - Biomerieux, Inc
item Parker, Craig
item ENDTZ, HUBERT - Desiderio Finamore Veterinary Research Institute (FEPAGRO)

Submitted to: Journal of Bacteriology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/22/2015
Publication Date: 7/1/2015
Citation: Heikema, A.P., Islam, Z., Horst-Kreft, D., Huizinga, R., Jacobs, B.C., Wagenaar, J.A., Poly, F., Guerry, P., Van Belkam, A., Parker, C., Endtz, H.P. 2015. Distinct Campylobacter jejuni capsular types are related to Guillain-Barré syndrome in The Netherlands and Bangladesh. Journal of Bacteriology. doi: 10.1016/j.cmi.2015.05.031.

Interpretive Summary: Guillain-Barré syndrome (GBS), a debilitating and sometimes fatal paralysis, occurs in around one in thousand cases following an infection with the intestinal pathogen Campylobacter jejuni. It is established that sialylated lipooligosaccharides (LOS) of C. jejuni that mimic human gangliosides are a crucial virulence factor in GBS development. Frequent detection of C. jejuni with sialylated LOS in stools derived from patient with uncomplicated enteritis, however, implies that additional bacterial factors may contribute to the onset of neurological disease. To assess whether the capsule is a marker for GBS more globally, the capsular genotype of a large and heterogeneous collection of GBS- and uncomplicated enteritis-associated C. jejuni strains was determined. Capsule genotyping of C. jejuni strains from the Netherlands revealed that three capsule types, HS4c, HS2, and HS1/44c were over-represented in the GBS-associated strain collection. When GBS and enteritis control strains were compared, capsular types HS1/44c and HS4c were significantly associated with GBS (P = 0.05 and P = 0.01 respectively). Correlation of LOS class and capsular type resulted in the identification of conserved LOS class/capsular type combinations that were dominant in the GBS strain collection. In a GBS-associated strain collection from Bangladesh, capsular types HS23/36c, HS19, and HS41 were most prevalent. Multi locus sequence typing revealed restricted genetic diversity for strain populations with the capsular types HS2, HS19 and HS41. We conclude that capsular types HS1/44c, HS2, HS4c, HS19, HS23/36c and HS41 are markers for GBS. Besides a crucial role for sialylated LOS of C. jejuni in GBS pathogenesis, the identified capsules may contribute to GBS susceptibility.

Technical Abstract: An infection with the intestinal pathogen Campylobacter jejuni leads to Guillain-Barré syndrome (GBS) in around one in thousand cases. It is established that sialylated lipooligosaccharides (LOS) of C. jejuni are a crucial virulence factor in GBS development. Frequent detection of C. jejuni with sialylated LOS in stools derived from patient with uncomplicated enteritis, however, implies that additional bacterial factors may contribute to the onset of neurological disease. To assess whether the capsule is a marker for GBS more globally, the capsular genotype of a large and heterogeneous collection of GBS- and uncomplicated enteritis-associated C. jejuni strains was determined. Capsule genotyping of C. jejuni strains from the Netherlands revealed that three capsule types, HS4c, HS2, and HS1/44c were over-represented in the GBS-associated strain collection. When GBS and enteritis control strains were compared, capsular types HS1/44c and HS4c were significantly associated with GBS (P = 0.05 and P = 0.01 respectively). Correlation of LOS class and capsular type resulted in the identification of conserved LOS class/capsular type combinations that were dominant in the GBS strain collection. In a GBS-associated strain collection from Bangladesh, capsular types HS23/36c, HS19, and HS41 were most prevalent. Multi locus sequence typing revealed restricted genetic diversity for strain populations with the capsular types HS2, HS19 and HS41. We conclude that capsular types HS1/44c, HS2, HS4c, HS19, HS23/36c and HS41 are markers for GBS. Besides a crucial role for sialylated LOS of C. jejuni in GBS pathogenesis, the identified capsules may contribute to GBS susceptibility.