Unique Yersinia enterocolitica Type May Cause Illness Through Inflammatory Response
A prevalent type of Yersinia enterocolitica may cause gastrointestinal disease through an inflammatory mechanism that differs from other pathogenic Y. enterocolitica biotypes (BTs), according to a new study published in Pathogens and conducted by researchers from New Zealand's Institute for Public Health and Forensic Science (PHF Science).
Yersiniosis is the second most frequently notified foodborne illness in New Zealand, where Y. enterocolitica BT 1A accounts for approximately 20–30 percent of annual notifications. Unlike other Y. enterocolitica types known to cause illness, BT 1A lacks several recognized virulence genes associated with the pathogen's ability to attach to and invade human cells, which has long raised questions about its clinical significance.
In this context, to investigate the pathogenic potential of Y. enterocolitica BT 1A, the researchers analyzed whole genome sequencing (WGS) data from 470 Y. enterocolitica isolates and conducted in vitro laboratory experiments using two-dimensional (2D) intestinal cell cultures and a three-dimensional (3D) organ-on-a-chip model of the human intestine.
Alternative, Inflammation-Mediated Mechanism May Cause GI Illness
Genomic analysis confirmed that all 286 BT 1A isolates lacked several key virulence determinants, including the ail gene and genes associated with the Yersinia virulence plasmid (pYV). In 2D intestinal cell assays, four BT 1A isolates also demonstrated significantly lower levels of attachment and invasion compared to BT 2/3 and BT 4 isolates, which are recognized as pathogenic.
However, in the 3D intestinal organ-on-a-chip model, a single BT 1A isolate elicited a significantly greater interleukin-8 (IL-8) inflammatory response than the BT 2/3 and BT 5 isolates tested. IL-8 is an inflammatory signaling protein involved in the body's immune response to infection.
The researchers suggested that this finding may indicate an alternative, inflammation-mediated mechanism through which BT 1A could contribute to gastrointestinal illness, despite lacking traditional virulence factors. However, they emphasized that additional research involving more isolates is necessary to establish the mechanism and its relevance to human disease.
Different Yersinia Biotypes Associated With Distinct Epidemiological Patterns
The study also analyzed 6,345 notified yersiniosis cases in New Zealand from 2018–2022, identifying differences in the age, ethnicity, and geographic distribution of infections associated with different Y. enterocolitica biotypes.
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Specifically, BT 1A was more frequently identified among adults of European or Other ethnicity, with the highest notification rates observed in New Zealand's South Island. In contrast, BT 2/3, the most commonly notified biotype, was more frequently identified among young children of Asian ethnicity, particularly in the country's northern region.
The researchers also found that 21 percent of BT 1A cases with a recorded illness onset date had an interval of at least 30 days between symptom onset and notification, compared to 6 percent of BT 2/3 cases. However, hospitalization rates were similar across BT 1A, BT 2/3, and BT 4, ranging from 13–15 percent among cases with available hospitalization information.
Implications and Recommendations
Although the findings did not establish the reasons for these epidemiological differences, the researchers highlighted the potential importance of underlying gastrointestinal conditions, host susceptibility, and differences in exposure.
Overall, the researchers concluded that distinguishing BT 1A infections from those caused by other Y. enterocolitica biotypes could improve public health investigations and surveillance. Further studies are needed to clarify BT 1A's role in human illness, identify potential alternative virulence mechanisms, and better characterize associated foodborne risk factors.
