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Virulence studies, in mice, of transposon-induced mutants of Staphylococcus aureus differing in capsule size
J C Lee1, M J Betley, C A Hopkins
1Channing Laboratory, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Abstract:
We used three related strains of Staphylococcus aureus to determine whether capsule size influenced bacterial virulence. Strain SA1 mucoid elaborated a large capsule demonstrable by transmission electron microscopy (TEM). Nonmucoid isolates were derived from strain SA1 mucoid by Tn551 insertional mutagenesis. By TEM, strain JL24 produced a "microcapsule," whereas strain JL25 was unencapsulated. Strain SA1 mucoid had a 50% lethal dose for mice greater than 3,000-fold lower than that of strains JL24 and JL25. Quantitative cultures of blood and kidney from animals challenged intravenously revealed that strain SA1 mucoid was cleared less readily from the bloodstream and kidneys than the nonmucoid mutants. In an in vitro assay, only strain SA1 mucoid demonstrated antibody-dependent, complement-mediated opsonophagocytosis by human leukocytes. Strains JL24 and JL25 were opsonized for phagocytosis by complement alone. Thus a highly encapsulated strain of S. aureus was more virulent in mice than two related nonmucoid strains. The microencapsulated mutant was not more virulent than the unencapsulated mutant.
Insights
A large capsule on Staphylococcus aureus significantly increases bacterial virulence in mice. Smaller or absent capsules reduce virulence, indicating capsule size is critical for S. aureus infection severity.
Area of Science:
- Microbiology
- Immunology
- Infectious Diseases
Background:
- Staphylococcus aureus is a significant human pathogen.
- Bacterial capsule production is a key virulence factor.
- The relationship between capsule size and S. aureus virulence requires further elucidation.
Purpose of the Study:
- To investigate the impact of Staphylococcus aureus capsule size on bacterial virulence.
- To compare the virulence of encapsulated and non-encapsulated S. aureus strains in a murine model.
Main Methods:
- Generated three related S. aureus strains with varying capsule sizes using Tn551 mutagenesis.
- Assessed virulence in mice via lethal dose (LD50) and quantitative cultures of blood and kidneys.
- Evaluated in vitro opsonophagocytosis by human leukocytes using complement and antibodies.
Main Results:
- The highly encapsulated S. aureus strain (SA1 mucoid) exhibited significantly lower LD50 in mice compared to non-encapsulated strains (JL24, JL25).
- SA1 mucoid demonstrated reduced clearance from blood and kidneys post-intravenous challenge.
- Only the highly encapsulated strain underwent antibody-dependent, complement-mediated opsonophagocytosis; non-encapsulated strains were opsonized by complement alone.
Conclusions:
- Large capsule size in Staphylococcus aureus is directly correlated with increased virulence in a murine model.
- Microencapsulated mutants showed no increased virulence compared to unencapsulated strains, suggesting a threshold effect for capsule-mediated virulence.