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Updated: Jun 20, 2026
Humanized Mouse Model to Study Bacterial Infections Targeting the Microvasculature
Published on: April 1, 2014
CD46 transgenic mouse model of necrotizing fasciitis caused by Streptococcus pyogenes infection
Hidenori Matsui1, Yukie Sekiya, Masahiko Nakamura
1Kitasato Institute for Life Sciences and Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan. hmatsui@lisci.kitasato-u.ac.jp
Abstract:
We developed a human CD46-expressing transgenic (Tg) mouse model of subcutaneous (s.c.) infection into both hind footpads with clinically isolated 11 group A streptococcus (GAS) serotype M1 strains. When the severity levels of foot lesions at 72 h and the mortality rates by 336 h were compared after s.c. infection with 1x10(7) CFU of each GAS strain, the GAS472 strain, isolated from the blood of a patient suffering from streptococcal toxic shock syndrome (STSS), induced the highest severity levels and mortality rates. GAS472 led to a 100% mortality rate in CD46 Tg mice after only 168 h postinfection through the supervention of severe necrotizing fasciitis (NF) of the feet. In contrast, GAS472 led to a 10% mortality rate in non-Tg mice through the supervention of partial necrotizing cutaneous lesions of the feet. The footpad skin sections of CD46 Tg mice showed hemorrhaging and necrotic striated muscle layers in the dermis, along with the exfoliation of epidermis with intracellular edema until 48 h after s.c. infection with GAS472. Thereafter, the bacteria proliferated, reaching a 90-fold or 7-fold increase in the livers of CD46 Tg mice or non-Tg mice, respectively, for 24 h between 48 and 72 h after s.c. infection with GAS472. As a result, the infected CD46 Tg mice appeared to suffer severe liver injuries. These findings suggest that human CD46 enhanced the progression of NF in the feet and the exponential growth of bacteria in deep tissues, leading to death.
Insights
A new mouse model shows human CD46 enhances group A Streptococcus (GAS) infections. CD46 transgenic mice developed severe necrotizing fasciitis and higher mortality, indicating CD46
Area of Science:
- Microbiology
- Immunology
- Pathology
Background:
- Group A Streptococcus (GAS) causes severe infections like streptococcal toxic shock syndrome (STSS) and necrotizing fasciitis (NF).
- The role of human CD46 in GAS pathogenesis, particularly in invasive infections, remains incompletely understood.
Purpose of the Study:
- To develop and characterize a human CD46-expressing transgenic (Tg) mouse model for studying subcutaneous (s.c.) GAS infections.
- To investigate the impact of human CD46 on the severity of GAS-induced necrotizing fasciitis and mortality.
Main Methods:
- Development of CD46 Tg mice.
- Subcutaneous infection of hind footpads with clinically isolated GAS M1 strains.
- Comparison of lesion severity and mortality rates between CD46 Tg and non-Tg mice.
- Histopathological analysis of infected tissues and assessment of bacterial load in organs.
Main Results:
- The GAS472 strain, isolated from an STSS patient, induced the highest mortality and lesion severity in CD46 Tg mice.
- CD46 Tg mice exhibited 100% mortality due to severe necrotizing fasciitis within 168 hours post-infection.
- Non-Tg mice showed only 10% mortality with partial necrotizing cutaneous lesions.
- CD46 Tg mice displayed significant hemorrhaging, muscle necrosis, and epidermal changes, with a 90-fold increase in liver bacterial load compared to non-Tg mice.
Conclusions:
- Human CD46 significantly enhances the progression of necrotizing fasciitis in GAS foot infections.
- CD46 facilitates exponential bacterial growth in deep tissues, leading to increased systemic dissemination and mortality.
- The CD46 Tg mouse model is valuable for studying GAS pathogenesis and evaluating potential therapeutics for invasive infections.
