Abstract
Campylobacter jejuni causes more than 2 million cases of gastroenteritis annually in the United States, and is also linked to the autoimmune sequelae Guillan–Barre syndrome (GBS). GBS often results in flaccid paralysis, as the myelin sheaths of nerve cells are degraded by the adaptive immune response. Certain strains of C. jejuni modify their lipooligosaccharide (LOS) with the addition of neuraminic acid, resulting in LOS moieties that are structurally similar to gangliosides present on nerve cells. This can trigger GBS in a susceptible host, as antibodies generated against C. jejuni can cross-react with gangliosides, leading to demyelination of nerves and a loss of signal transduction. The goal of this study was to develop a quantitative PCR (qPCR) method and use whole genome sequencing data to detect the Campylobacter sialyltransferase (cst) genes responsible for the addition of neuraminic acid to LOS. The qPCR method was used to screen a library of 89 C. jejuni field samples collected by the Food and Drug Administration Pacific Northwest Lab (PNL) as well as clinical isolates transferred to PNL. In silico analysis was used to screen 827 C. jejuni genomes in the FDA GenomeTrakr SRA database. The results indicate that a majority of C. jejuni strains could produce LOS with ganglioside mimicry, as 43.8% of PNL isolates and 46.9% of the GenomeTrakr isolates lacked the cst genes. The methods described in this study can be used by public health laboratories to rapidly determine whether a C. jejuni isolate has the potential to induce GBS. Based on these results, a majority of C. jejuni in the PNL collection and submitted to GenomeTrakr have the potential to produce LOS that mimics human gangliosides.
Highlights
Campylobacter jejuni is a leading bacterial cause of gastroenteritis in the United States and worldwide (Tauxe, 1992; Kaakoush et al, 2015; CDC, 2017)
The results of this study indicate that the majority of C. jejuni in GenomeTrakr and the FDA Pacific Northwest Laboratory collection have the potential to produce LOS that mimics gangliosides
A rapid quantitative PCR (qPCR) method was developed to detect the cst-II and cst-III genes based on previous work demonstrating that these genes are required for the addition of sialic acid to Campylobacter LOS (Gilbert et al, 2002; Godschalk et al, 2004; Yuki, 2007; Parker et al, 2008)
Summary
Campylobacter jejuni is a leading bacterial cause of gastroenteritis in the United States and worldwide (Tauxe, 1992; Kaakoush et al, 2015; CDC, 2017). Infection is usually linked to the consumption of contaminated food or water, especially poultry products (Konkel et al, 2001; Sahin et al, 2015; Skarp et al, 2016). One gram of cecal contents may contain greater than 108 CFU of C. jejuni, and can cross contaminate C. jejuni-free chicken carcasses during processing (Garcia-Sanchez et al, 2017; Johnson et al, 2017). Cross-contamination in the kitchen can lead to the introduction of C. jejuni into other food products (Sahin et al, 2015; Skarp et al, 2016)
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