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A Mouse Model to Assess Innate Immune Response to Staphylococcus aureus Infection
Published on: February 28, 2019
Biofilm-Forming Methicillin-Resistant Staphylococcus aureus Survive in Kupffer Cells and Exhibit High Virulence in
Takuto Oyama1, Motoyasu Miyazaki2, Michinobu Yoshimura3
1Department of Plastic, Reconstructive and Aesthetic Surgery, Faculty of Medicine, Fukuoka University, Fukuoka 814-0180, Japan. oyt1974@yahoo.co.jp.
Abstract:
Although Staphylococcus aureus is part of the normal body flora, heavy usage of antibiotics has resulted in the emergence of methicillin-resistant strains (MRSA). MRSA can form biofilms and cause indwelling foreign body infections, bacteremia, soft tissue infections, endocarditis, and osteomyelitis. Using an in vitro assay, we screened 173 clinical blood isolates of MRSA and selected 20 high-biofilm formers (H-BF) and low-biofilm formers (L-BF). These were intravenously administered to mice and the general condition of mice, the distribution of bacteria, and biofilm in the liver, lung, spleen, and kidney were investigated. MRSA count was the highest in the liver, especially within Kupffer cells, which were positive for acid polysaccharides that are associated with intracellular biofilm. After 24 h, the general condition of the mice worsened significantly in the H-BF group. In the liver, bacterial deposition and aggregation and the biofilm-forming spot number were all significantly greater for H-BF group than for L-BF. CFU analysis revealed that bacteria in the H-BF group survived for long periods in the liver. These results indicate that the biofilm-forming ability of MRSA is a crucial factor for intracellular persistence, which could lead to chronic infections.
Insights
Methicillin-resistant Staphylococcus aureus (MRSA) strains that form more biofilms cause more severe infections in mice. Biofilm formation is key to MRSA
Area of Science:
- Microbiology
- Infectious Diseases
- Medical Research
Background:
- Antibiotic resistance has led to the rise of methicillin-resistant Staphylococcus aureus (MRSA).
- MRSA can cause severe infections and form biofilms, which are microbial communities encased in a self-produced matrix.
- Biofilm formation is a significant virulence factor in MRSA pathogenesis.
Purpose of the Study:
- To investigate the role of biofilm formation in MRSA pathogenesis and infection severity.
- To compare the in vivo behavior of high-biofilm forming (H-BF) and low-biofilm forming (L-BF) MRSA strains.
Main Methods:
- Screening of 173 clinical MRSA blood isolates using an in vitro biofilm assay.
- Selection of 20 H-BF and 20 L-BF MRSA strains.
- Intravenous administration of selected MRSA strains to mice to assess infection progression, bacterial distribution, and biofilm formation in organs (liver, lung, spleen, kidney).
Main Results:
- MRSA bacterial counts were highest in the liver, particularly within Kupffer cells, which showed intracellular biofilm markers.
- Mice infected with H-BF MRSA exhibited significantly worsened general condition within 24 hours compared to those infected with L-BF strains.
- H-BF MRSA led to greater bacterial deposition, aggregation, and biofilm formation in the liver, with prolonged bacterial survival.
Conclusions:
- The ability of MRSA to form biofilms is a critical factor in its ability to persist intracellularly.
- Biofilm formation contributes significantly to the severity of MRSA infections, particularly in the liver.
- Targeting biofilm formation may be a promising strategy for combating chronic MRSA infections.
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