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Production of toxic shock syndrome toxin 1 in a mouse model of Staphylococcus aureus abscess formation
J C Lee1, N E Perez, C A Hopkins
1Channing Laboratory, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Abstract:
A mouse model of abscess formation is described in which toxic shock syndrome toxin 1 (TSST-1) is produced by Staphylococcus aureus in vivo. Mice injected intravenously with S. aureus developed renal abscesses within 4-7 days. Kidneys excised from infected mice were cultured quantitatively, and extracts from the kidneys were assayed for TSST-1 with use of a competitive enzyme-linked immunosorbent assay. Animals with less than 10(7) S. aureus/g of kidney had less than 6 ng of TSST-1/mL of extract. Toxin levels ranged from less than 6 ng/mL to 271 ng/mL in kidney extracts from mice with greater than 10(7) S. aureus/g of kidney. Urine from infected mice also contained measurable levels of TSST-1 (range, less than 6-728 ng/mL). Mice developed serum antibodies to TSST-1 by 2 weeks after challenge. Serum samples collected 5-7 days after bacterial challenge did not show biochemical changes typical of a toxic shock-like illness in these animals.
Insights
This study details a mouse model for abscess formation where Staphylococcus aureus produces toxic shock syndrome toxin 1 (TSST-1). The model effectively demonstrates renal abscesses and TSST-1 production in infected mice.
Area of Science:
- Microbiology
- Immunology
- Pathology
Background:
- Toxic Shock Syndrome Toxin 1 (TSST-1) is a key virulence factor produced by Staphylococcus aureus.
- Understanding the in vivo production and effects of TSST-1 is crucial for developing effective treatments.
Purpose of the Study:
- To establish and characterize a mouse model for studying TSST-1 production during Staphylococcus aureus-induced abscess formation.
- To quantify TSST-1 levels in renal abscesses and urine of infected mice.
- To investigate the development of antibodies against TSST-1.
Main Methods:
- Intravenous injection of Staphylococcus aureus into mice to induce renal abscesses.
- Quantitative culture of kidney tissues to determine bacterial load.
- Competitive enzyme-linked immunosorbent assay (ELISA) to measure TSST-1 levels in kidney extracts and urine.
- Serological analysis to detect anti-TSST-1 antibodies.
Main Results:
- Mice developed renal abscesses 4-7 days post-infection.
- TSST-1 levels correlated with bacterial load in kidneys (ranging from <6 ng/mL to 271 ng/mL).
- Measurable TSST-1 was detected in the urine of infected mice (ranging from <6 ng/mL to 728 ng/mL).
- Mice developed serum antibodies to TSST-1 within two weeks.
Conclusions:
- The developed mouse model effectively replicates Staphylococcus aureus-induced renal abscesses and TSST-1 production in vivo.
- The model allows for the quantification of TSST-1 in both tissue and urine, aiding in understanding toxin dissemination.
- While antibodies develop, early-stage infections did not exhibit typical toxic shock-like biochemical changes, suggesting a complex host-pathogen interaction.