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The role of pneumolysin in ocular infections with Streptococcus pneumoniae
M K Johnson1, J A Hobden, M Hagenah
1Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70112.
Abstract:
Pneumolysin, a cytolytic protein produced by Streptococcus pneumoniae, has many properties which suggest it may be an important virulence factor in pneumococcal ocular infections. To directly test this possibility, we have constructed pneumolysin-negative strains of S. pneumoniae and compared their virulence with that of the wild type in a rabbit model of intracorneal infection. A pneumolysin-negative strain produced by chemical mutagenesis (probably a point mutant) was found to be no less virulent than the parent strain. However, a strain bearing a deletion in the pneumolysin gene showed greatly reduced virulence. This strain produced less pathology while showing significantly higher bacterial counts. These results suggest that a property of the pneumolysin molecule other than its cytolytic (hemolytic) activity may be involved in its pathogenic mechanism of action. This property may be the ability to activate complement, known to be a function of pneumolysin, which results in influx of PMNs, reducing the bacterial counts but also producing tissue damage.
Insights
Pneumolysin (PLY) from Streptococcus pneumoniae may cause eye infections. A PLY-negative strain showed reduced virulence, suggesting a non-cytolytic function, possibly complement activation, contributes to pneumococcal eye infection severity.
Area of Science:
- Ophthalmology
- Microbiology
- Immunology
Background:
- Streptococcus pneumoniae is a leading cause of bacterial keratitis.
- Pneumolysin (PLY), a pore-forming toxin produced by S. pneumoniae, is implicated as a key virulence factor.
- The precise role of PLY in pneumococcal ocular infections remains to be fully elucidated.
Purpose of the Study:
- To investigate the role of pneumolysin (PLY) in the pathogenesis of pneumococcal ocular infections.
- To determine if the cytolytic activity of PLY is essential for virulence in the rabbit cornea model.
- To explore alternative mechanisms of PLY virulence beyond cytolysis.
Main Methods:
- Construction of pneumolysin-negative Streptococcus pneumoniae strains via chemical mutagenesis and gene deletion.
- Intracorneal infection model in rabbits using wild-type and pneumolysin-negative S. pneumoniae strains.
- Assessment of bacterial counts, corneal pathology, and inflammatory cell infiltration.
Main Results:
- A chemically generated pneumolysin-negative mutant exhibited virulence comparable to the wild-type strain.
- A pneumolysin gene deletion mutant displayed significantly reduced virulence, with less corneal pathology.
- The deletion mutant showed higher bacterial loads compared to the wild-type, despite reduced pathology.
Conclusions:
- Pneumolysin's cytolytic activity is not the sole determinant of its virulence in pneumococcal keratitis.
- A non-cytolytic function of pneumolysin, potentially complement activation leading to PMN influx, may contribute to ocular pathogenesis.
- Further research is warranted to elucidate the specific non-cytolytic mechanisms of pneumolysin in eye infections.