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Updated: Mar 25, 2026
Humanized Mouse Model to Study Bacterial Infections Targeting the Microvasculature
Published on: April 1, 2014
A highly susceptible CD46 transgenic mouse model of subcutaneous infection with Streptococcus dysgalactiae subspecies
Haruno Yoshida1, Tetsufumi Takahashi2, Masahiko Nakamura2
1Kitasato Institute for Life Sciences and Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
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.
Insights
Human membrane cofactor protein (CD46) acts as a receptor for Streptococcus dysgalactiae subspecies equisimilis (SDSE), increasing mortality and invasive disease, including arthritis and renal failure, in infected mice.
Area of Science:
- Microbiology
- Immunology
- Pathogenesis
Background:
- Streptococcus dysgalactiae subspecies equisimilis (SDSE) causes severe infections, similar to Group A Streptococcus (GAS).
- Human membrane cofactor protein (CD46) is a complement regulatory protein and a known receptor for pathogens like GAS.
- SDSE strain GGS_124 was isolated from a patient with streptococcal toxic shock syndrome.
Purpose of the Study:
- To investigate the role of CD46 in SDSE infection and disease development.
- To determine if CD46 influences the outcome of subcutaneous SDSE infection.
Main Methods:
- Infection of CD46-expressing transgenic (Tg) and non-Tg mice with SDSE strain GGS_124.
- Monitoring of bacterial colonization, mortality rates, and development of clinical signs such as arthritis, abscesses, and renal failure.
Main Results:
- CD46 Tg mice exhibited significantly higher mortality rates (33%) compared to non-Tg mice (0%).
- All surviving CD46 Tg mice developed ankle arthritis, while non-Tg mice did not.
- CD46 Tg mice developed abscesses and renal failure, indicating invasive disease progression.
Conclusions:
- CD46 facilitates the entry of SDSE into deep tissues, promoting invasive streptococcal diseases.
- The host receptor CD46 plays a critical role in the pathogenesis of SDSE infections, leading to severe outcomes.
