Abstract
Campylobacter jejuni is the most common cause of bacterial diarrheal disease in the world. Clinical outcomes of infection can range from asymptomatic infection to life-threatening extraintestinal infections. This variability in outcomes for infected patients has raised questions as to whether genetic differences between C. jejuni isolates contribute to their likelihood of causing severe disease. In this study, we compare the genomes of ten C. jejuni isolates that were implicated in extraintestinal infections with reference gastrointestinal isolates, in order to identify unusual patterns of sequence variation associated with infection outcome. We identified a collection of genes that display a higher burden of uncommon mutations in invasive isolates compared with gastrointestinal close relatives, including some that have been previously linked to virulence and invasiveness in C. jejuni. Among the top genes identified were mreB and pgp1, which are both involved in determining cell shape. Electron microscopy confirmed morphological differences in isolates carrying unusual sequence variants of these genes, indicating a possible relationship between extraintestinal infection and changes in cell morphology.
Highlights
Campylobacter jejuni is the most common bacterial cause of diarrhea in the world [1]
We found that the patterns of sequence variation we identified in our study are unlikely to have strong predictive value in identifying other strains of invasive C. jejuni, they are indicative of a shift in selection pressures that occurs during extraintestinal infection
A NeighborNet diagram of relatedness of the strains used in our study indicated that the randomly selected ST50 strains we included in our analysis were distantly related to the New Zealand invasive isolates, and further analysis of the ST50 clade indicated that our strains were members of a rare subgroup (Fig. S1)
Summary
Campylobacter jejuni is the most common bacterial cause of diarrhea in the world [1]. Campylobacter bacteremia appears to originate from acute colitis, indicating a progression from diarrheal disease to extraintestinal infection in a subset of cases [6]. While extraintestinal infections with members of the genus Campylobacter disproportionately affect the very young, the very old and the immunocompromised, the wide range of disease presentations cannot be explained purely by host factors, indicating that differences in the bacterial pathogen may contribute [2, 6, 7]. Cytotoxin production, motility and the ability to adhere to epithelial cells have been implicated as genetic factors in members of the genus Campylobacter that are associated with disease presentation [8,9,10].
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