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      Clinical and epidemiological analysis of Campylobacter fetus subsp. fetus infections in humans and comparative genetic analysis with strains isolated from cattle

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          Abstract

          Background

          Campylobacter fetus subspecies fetus (CFF) is an important pathogen for both cattle and humans. We performed a systematic epidemiological and clinical study of patients and evaluated the genetic relatedness of 17 human and 17 bovine CFF isolates by using different genotyping methods. In addition, the serotype, the dissemination of the genomic island containing a type IV secretion system (T4SS) and resistance determinants for tetracycline and streptomycin were also evaluated.

          Methods

          The isolates from patients diagnosed with CFF infection as well as those from faecal samples of healthy calves were genotyped using pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), as well as single locus sequence typing (SLST) targeting cmp1 and cmp2 genes encoding two major outer membrane proteins in CFF. The presence of the genomic island and identification of serotype was determined by PCRs targeting genes of the T4SS and the sap locus, respectively. Tetracycline and streptomycin resistance phenotypes were determined by minimal inhibitory concentration. Clinical data obtained from medical records and laboratory data were supplemented by data obtained via telephone interviews with the patients and treating physicians.

          Results

          PFGE analysis defined two major clusters; cluster A containing 16 bovine (80 %) isolates and cluster B containing 13 human (92 %) isolates, suggesting a host preference. Further genotypic analysis using MLST, SLST as well as sap and T4SS PCR showed the presence of genotypically identical isolates in cattle and humans. The low diversity observed within the cmp alleles of CFF corroborates the clonal nature of this pathogen. The genomic island containing the tetracycline and streptomycin resistance determinants was found in 55 % of the isolates in cluster A and correlated with phenotypic antibiotic resistance.

          Conclusions

          Most human and bovine isolates were separated on two phylogenetic clusters. However, several human and bovine isolates were identical by diverse genotyping methods, indicating a possible link between strains from these two hosts.

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          Most cited references45

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          The versatile bacterial type IV secretion systems.

          Bacteria use type IV secretion systems for two fundamental objectives related to pathogenesis--genetic exchange and the delivery of effector molecules to eukaryotic target cells. Whereas gene acquisition is an important adaptive mechanism that enables pathogens to cope with a changing environment during invasion of the host, interactions between effector and host molecules can suppress defence mechanisms, facilitate intracellular growth and even induce the synthesis of nutrients that are beneficial to bacterial colonization. Rapid progress has been made towards defining the structures and functions of type IV secretion machines, identifying the effector molecules, and elucidating the mechanisms by which the translocated effectors subvert eukaryotic cellular processes during infection.
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            Horizontal gene transfer in human pathogens.

            Horizontal gene transfer has a tremendous impact on the genome plasticity, adaptation and evolution of bacteria. Horizontally transferred mobile genetic elements are involved in the dissemination of antibiotic resistance and virulence genes, thus contributing to the emergence of novel "superbugs". This review provides update on various mechanisms of horizontal gene transfer and examines how horizontal gene transfer contributes to the evolution of pathogenic bacteria. Special focus is paid to the role horizontal gene transfer plays in pathogenicity of the emerging human pathogens: hypervirulent Clostridium difficile and Escherichia coli (including the most recent haemolytic uraemic syndrome outbreak strain) and methicillin-resistant Staphylococcus aureus (MRSA), which have been associated with largest outbreaks of infection recently.
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              Campylobacter bacteremia: clinical features and factors associated with fatal outcome.

              Campylobacter bacteremia is uncommon. The influence of underlying conditions and of the impact of antibiotics on infection outcome are not known. From January 2000 through December 2004, 183 episodes of Campylobacter bacteremia were identified in 23 hospitals in the Paris, France, area. The medical records were reviewed. Characteristics of bacteremia due to Campylobacter fetus and to other Campylobacter species were compared. Logistic regression analysis was performed to identify risk factors for fatal outcome within 30 days. Most affected patients were elderly or immunocompromised. C. fetus was the most commonly identified species (in 53% of patients). The main underlying conditions were liver disease (39%) and cancer (38%). The main clinical manifestations were diarrhea (33%) and skin infection (16%). Twenty-seven patients (15%) died within 30 days. Compared with patients with bacteremia due to other Campylobacter species, patients with C. fetus bacteremia were older (mean age, 69.5 years vs. 55.6 years; P = .001) and were more likely to have cellulitis (19% vs. 7%; P = .03), endovascular infection (13% vs. 1%; P = .007), or infection associated with a medical device (7% vs. 0%; P = .02). Independent risk factors for death were cancer (odds ratio [OR], 5.1; 95% confidence interval [CI], 1.2-20.8) and asymptomatic infection (OR, 6.7; 95% CI, 1.5-29.4) for C. fetus bacteremia, the absence of prescription of appropriate antibiotics (OR, 12.2; 95% CI, 0.9-157.5), and prescription of third-generation cephalosporins (OR, 10.2; 95% CI, 1.9-53.7) for bacteremia caused by other species. Campylobacter bacteremia occurs mainly in immunocompromised patients. Clinical features and risk factors of death differ by infection species.
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                Author and article information

                Contributors
                robert.escher@spital-emmental.ch
                Journal
                BMC Infect Dis
                BMC Infect. Dis
                BMC Infectious Diseases
                BioMed Central (London )
                1471-2334
                14 May 2016
                14 May 2016
                2016
                : 16
                : 198
                Affiliations
                [ ]Institute of Veterinary Bacteriology, Vetsuisse Faculty, University of Bern, Bern, Switzerland
                [ ]Department of Medicine, Spital Emmental, Burgdorf, Switzerland
                [ ]Institute for Infectious Diseases, University of Bern, Bern, Switzerland
                [ ]Current address: Institute of Virology and Immunology, University of Bern, Bern, Switzerland
                Article
                1538
                10.1186/s12879-016-1538-7
                4868008
                27177684
                229fa2b7-3104-4eef-941a-f2444de51a7e
                © Escher et al. 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 23 February 2015
                : 5 May 2016
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2016

                Infectious disease & Microbiology
                campylobacter fetus subspecies fetus,epidemiology,multilocus sequence typing (mlst),pulsed-field gel electrophoresis (pfge),major outer membrane protein (momp),type iv secretion system (t4ss)

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