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Arcobacter (A.) spp. is a gram-negative, motile and spiral-shaped bacterium belonging together with Campylobacter (C.) and Sulfurospirillum to the family of Campylobacteraceae. At present, 18 Arcobacter species have been characterized with A. butzleri as the most important and predominant species associated with human diseases, such as gastroenteritis, bacteremia or septicaemia. A. butzleri have been rated a serious hazard to human health by the International Commission on Microbiological Specifications for Foods in 2002. The bacteria have become more important in public health due to their presence in different sources such as animals including various food products of animal origin and water. However, the most frequent source of human A. butzleri infection is contaminated undercooked poultry meat and water. In few studies several authors demonstrated that A. butzleri is the fourth most common Campylobacterales species recovered from patients suffering from. Reported clinical signs of an A. butzleri infection are diarrhea associated with abdominal pain, nausea and vomiting or more rarely fever. Compared to C. jejuni, A. butzleri caused more watery and persistent, but less acute and bloody diarrhea. As human infections with A. butzleri are not routinely investigated, the relevance of this pathogen could not be determined so far. However, a few case reports and some outbreak data on human infection with A. butzleri are available indicating that A. butzleri is a truly human pathogen.
Although some progress has been made over the past decade, the knowledge about the pathogenic mechanisms and immune host responses of A. butzleri is still scarce. Several putative virulence determinants homologous to C. jejuni, were identified in the genome sequence of A. butzleri RM4018, while other virulence-associated genes of C. jejuni are missing. Results from phenotypic assays revealed adhesive, invasive and cytotoxic capabilities of A. butzleri on several cell lines in vitro. The barrier dysfunction caused by A. butzleri infection in monolayers of the human colon cell line HT-29/B6 highlights potential mechanisms by which diarrhea can be induced in human. This work focused on the investigation of virulence mechanisms of A. butzleri including its interactions with intestinal epithelial cells in vitro. Chapter 1 provides a literature review that emphasises the relevance of A. butzleri in human and veterinary public health. In the first study (Chapter 2), the presence of virulence genes homologous to those of C. jejuni and other enteric pathogens was investigated in several A. butzleri strains. Further the adhesive and invasive abilities of several A. butzleri strains on two different human intestinal epithelial cell lines (HT-29 and Caco-2) were demonstrated. No correlation was observed between putative virulence gene patterns and adhesive or invasive phenotypes with the tested cell lines; also the putative functional domains of CiaB, CadF and Cj1349 in the amino acid sequences showed no correlation with the different adhesive and invasive phenotypes. The aim of the second study (Chapter 3) was to obtain additional information on the pathogenicity and the pathomechanisms of A. butzleri strains. A. butzleri was investigated on two further epithelial cell lines to characterize different epithelial cell interactions and strain-specific pathomechanisms. The ability of A. butzleri strains for adhesion, invasion and cytotoxicity in human (HT-29/B6) and porcine (IPEC-J2) intestinal epithelial cell lines could be demonstrated. These A. butzleri strains were able to influence the transepithelial electrical resistance. The A. butzleri strain specific pathomechanisms has been observed with the human colon cell line HT-29/B6. Furthermore, A. butzleri induced systemic immune response in gnotobiotic IL-10 deficient mice in a strain-dependent manner (Chapter 4). Taken all data together, these findings emphasize the enteric pathogenic potential and strain-specific pathomechanisms of A. butzleri.