title: Experimental model of infection with non-toxigenic strains of Corynebacterium diphtheriae and development of septic arthritis.
abstract: Corynebacterium diphtheriae is a well-known cause of localized respiratory tract infections. However, this micro-organism can also be associated with invasive infections, such as endocarditis, septic arthritis and osteomyelitis. Invasive infections are often caused by non-toxigenic strains. To set up an in vivo experimental model of C. diphtheriae infection, mice were infected intravenously with different doses (ranging from 1 x 10(7) to 5 x 10(8) bacteria per mouse) of three non-toxigenic strains, namely ISS-4749, ISS-4746 and ISS-3319. Similar mortality rates were observed with the three strains, with an LD50 ranging from 9 x 10(7) to 1.2 x 10(8). All strains were arthritogenic, although to different extents. ISS-4749 and ISS-4746 infection resulted in a maximum of 60 and 50 %, respectively, of animals with articular lesions, while in the ISS-3319-infected group only 25 % were positive. There were differences in systemic and joint cytokine production in the three experimental groups. ISS-4749- and ISS-4746-infected mice exhibited higher local levels of interleukin (IL)-6 and IL-1beta than ISS-3319-infected animals. At systemic levels, ISS-3319 was able to induce early and sustained production of interferon-gamma (IFN-gamma), but not IL-6. Conversely, infection with the other strains resulted in high IL-6, but not IFN-gamma, production. In conclusion, an experimental model of C. diphtheriae infection was set up, with development of septic arthritis. This model could be useful in studies on the pathogenicity and characterization of virulence factors other than toxin production.
authors.affiliation: Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Via del Giochetto, 06122 Perugia, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Puliti
authors.affiliation: Dipartimento di Malattie Infettive, Parassitarie ed Immunomediate, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Roma, Italy.
authors.forename: Christina
authors.initials: C
authors.lastname: von Hunolstein
authors.affiliation: Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Via del Giochetto, 06122 Perugia, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Marangi
authors.affiliation: Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Via del Giochetto, 06122 Perugia, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Bistoni
authors.affiliation: Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Via del Giochetto, 06122 Perugia, Italy.
authors.forename: Luciana
authors.initials: L
authors.lastname: Tissi
mesh_terms: D000818:Animals; D001170:Arthritis, Infectious / Q000276:immunology* / Q000473:pathology; D003353:Corynebacterium diphtheriae; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007371:Interferon-gamma / Q000032:analysis / Q000378:metabolism; D007375:Interleukin-1 / Q000032:analysis / Q000378:metabolism; D015850:Interleukin-6 / Q000032:analysis / Q000378:metabolism; D007596:Joints / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D007371:Interferon-gamma