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Campylobacter coli clade 3 isolates induce rapid cell death in vitro
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology. (Clinical Microbiology)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology. (Clinical Microbiology)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology. (Clinical Microbiology)ORCID iD: 0000-0002-2111-9751
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.ORCID iD: 0000-0002-9692-8473
2019 (English)In: Applied and Environmental Microbiology, ISSN 0099-2240, E-ISSN 1098-5336, Vol. 85, no 5, article id UNSP e02993-18Article in journal (Refereed) Published
Abstract [en]

Campylobacter are major human enteropathogens. C. coli show less genetic diversity than C. jejuni and cluster into three clades, of which clade 1 includes most human and farm animal isolates while environmental C. coli mainly belong to clades 2 and 3. Recently, we whole genome-sequenced eight C. coli clade 2 and 3 isolates cultivated from water, and here we studied their interaction with human HT-29 colon cancer cells compared to clinical clade 1 isolates. All C. coli clade 3 isolates caused cell necrosis already 1-2 hours after inoculation, whereas none of the clade 1 and 2 isolates analyzed induced cell death. Isolates from clades 2 and 3 adhered better than clade 1 isolates to epithelial cells but all isolates induced similar levels of IL-8. Alignment and phylogenetic analysis of translated putative virulence genes cadF, flpA, iamA, ciaB and ceuE revealed clade-specific protein sequence variations with clade 1 and 2 sequences more closely related and clade 3 sequences further apart in general.Moreover, when RNA levels were measured, clade 3 isolates showed a significantly lower expression of cadF, iamA and ceuE than clade 2 isolates, while flpA levels were higher in clade 3 isolates. The cytolethal distending toxin genes were also expressed in clades 2 and 3 although there was no difference between clades. Our findings demonstrate differences between effects of C. coli clade 1, 2 and 3 isolates on human cells and suggest that C. coli clade 3 might be more virulent than clade 2 due to the observed cytotoxicity.

IMPORTANCECampylobacter coli is a common zoonotic cause of gastroenteritis in humans worldwide. The majority of infections are caused by C. coli clade 1 isolates, whereas infections due to clade 2 and 3 isolates are rare. Whether this depends on a low prevalence of clade 2 and 3 isolates in reservoirs important for human infections or their lower ability to cause human disease is unknown. Here, we studied the effects of C. coli clade 2 and 3 isolates on a human cell line. These isolates adhered to human cells to a higher degree than clinical clade 1 isolates. Furthermore, we could show that C. coli clade 3 isolates rapidly induced cell death suggesting differences in the virulence of C. coli The exact mechanism of cell death remains to be revealed but selected genes showed interesting clade-specific expression patterns.

Place, publisher, year, edition, pages
2019. Vol. 85, no 5, article id UNSP e02993-18
National Category
Microbiology in the medical area
Identifiers
URN: urn:nbn:se:uu:diva-372594DOI: 10.1128/AEM.02993-18ISI: 000459327600019PubMedID: 30578266OAI: oai:DiVA.org:uu-372594DiVA, id: diva2:1276162
Funder
Swedish Research Council FormasAvailable from: 2019-01-07 Created: 2019-01-07 Last updated: 2019-08-01Bibliographically approved

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Nilsson, Anna J. E.Kaden, ReneRautelin, Hilpi

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