CRISPR typing of Campylobacter jejuni reveals a link between CRISPR array preservation and Guillain-Barré syndrome

Abstract

Guillain-Barré syndrome (GBS) is a post-infection sequela of Campylobacter jejuni-induced enteritis. Clustered regularly interspaced short palindromic repeats and associated genes (CRISPR-Cas) confers adaptive immunity and plays role in virulence in many bacteria. We investigated C. jejuni CRISPR type (CT) to explore association of CRISPR-Cas with risk of developing GBS. We analysed CRISPR-Cas in C. jejuni isolated from 30 patients with GBS, 60 patients with enteritis and 52 healthy controls from Bangladesh. CRISPR types were determined by PCR followed by CRISPR array sequencing. Statistical and genomic analyses were performed using SPSS and multiple web-based software respectively. We found preserved CRISPR array was significantly more frequent in GBS-related strains than healthy control-related strains (P = 0.02, OR = 2.95). Increased CRISPR array length was significantly associated with GBS compared to healthy control- (P = 0.003, AUC = 0.7) and enteritis-related strains (P = 0.02, AUC = 0.65). We reported 38 new CT found among 70 CRISPR-preserving strains. CT of GBS-related strains were unique from enteritis- and healthy control-related strains. Eighty spacers, including 20 novel spacers, were identified among the CRISPR-preserving strains. CRISPR typing had more discriminatory power than PCR-based subtyping in enteritis- and healthy control-related strains. Further genomic analyses are warranted to elucidate role of the C. jejuni CRISPR array in GBS pathogenesis.