title: A highly susceptible CD46 transgenic mouse model of subcutaneous infection with Streptococcus dysgalactiae subspecies equisimilis.
abstract: The Streptococcus dysgalactiae subspecies equisimilis (SDSE) possesses clinical similarities to group A streptococcus (GAS) and has recently been recognized as a causative pathogen of life-threatening streptococcal infections. Human membrane cofactor protein (CD46), a complement regulatory protein ubiquitously expressed on every cell type except for erythrocytes, has been implicated as a receptor for human-specific pathogens including GAS. In the present report, SDSE strain GGS_124 was isolated from a patient suffering from streptococcal toxic shock syndrome. When CD46-expressing transgenic (Tg) and non-Tg mice were infected subcutaneously into a hind footpad with 1 × 10(7) colony-forming units of GGS_124, both CD46 Tg and non-Tg mice showed similar levels of colonization in the popliteal lymph nodes at day 3 after infection. However, the following differences were found between CD46 Tg and non-Tg mice after infection. First, there was a statistically significant difference in mortality rates between CD46 Tg (33%) and non-Tg (0%) mice within 35 days after infection. Second, all surviving CD46 Tg mice developed ankle arthritis at day 35 after infection, whereas non-Tg mice did not develop ankle arthritis on the infected hind paws. Finally, CD46 Tg mice developed a pus-filled abscess accompanied by renal failure at day 6 or later after infection. These observations suggest that CD46, the host cell-surface pathogen receptor, functioned to attract GGS_124 into deep tissues, so that the subcutaneous infection with GGS_124 induced invasive streptococcal diseases in CD46 Tg mice.
authors.affiliation: Kitasato Institute for Life Sciences and Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Haruno
authors.initials: H
authors.lastname: Yoshida
authors.affiliation: Center for Clinical Pharmacy and Clinical Sciences, School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Tetsufumi
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Center for Clinical Pharmacy and Clinical Sciences, School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Center for Clinical Pharmacy and Clinical Sciences, School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Anders
authors.initials: A
authors.lastname: Øverby
authors.affiliation: Kitasato Institute for Life Sciences and Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Kitasato Institute for Life Sciences and Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Kimiko
authors.initials: K
authors.lastname: Ubukata
authors.affiliation: Kitasato Institute for Life Sciences and Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan. Electronic address: hmatsui@lisci.kitasato-u.ac.jp.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Matsui
mesh_terms: D000818:Animals; D001170:Arthritis, Infectious / Q000276:immunology / Q000382:microbiology*; D004195:Disease Models, Animal; D004198:Disease Susceptibility / Q000276:immunology; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D051916:Membrane Cofactor Protein / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012772:Shock, Septic / Q000276:immunology / Q000382:microbiology*; D013290:Streptococcal Infections / Q000276:immunology / Q000382:microbiology*; D013291:Streptococcus
chemical_list: C497857:CD46 protein, human; D051916:Membrane Cofactor Protein
keywords: Ankle arthritis; CD46 transgenic mouse; Necrotic lesion; Pyogenic abscess; Streptococcal toxic shock syndrome; Streptococcus dysgalactiae subsp. equisimilis