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Identification of a secreted cholesterol-dependent cytolysin (mitilysin) from Streptococcus mitis.

ABSTRACT: We have detected a cholesterol-dependent cytolysin, which we have named mitilysin, in a small number of Streptococcus mitis isolates. We have sequenced the mitilysin gene from seven isolates of S. mitis. Comparisons with the pneumococcal pneumolysin gene show 15 amino acid substitutions. S. mitis appear to release mitilysin extracellularly. Certain alleles of mitilysin are not recognized by a monoclonal antibody raised to the related toxin pneumolysin. Based on enzyme-linked immunosorbent assay and neutralization assay results, one isolate of S. mitis may produce a further hemolytic toxin in addition to mitilysin. As genetic exchange is known to occur between S. mitis and Streptococcus pneumoniae, this finding may have implications for the development of vaccines or therapies for pneumococcal disease that are based on pneumolysin.

SUBMITTER: Jefferies J

PROVIDER: S-EPMC1797409 | biostudies-literature | 2007 Jan

REPOSITORIES: biostudies-literature

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Identification of a secreted cholesterol-dependent cytolysin (mitilysin) from Streptococcus mitis.

Jefferies Johanna J Nieminen Leena L Kirkham Lea-Ann LA Johnston Calum C Smith Andrew A Mitchell Tim J TJ

Journal of bacteriology 20061027 2

We have detected a cholesterol-dependent cytolysin, which we have named mitilysin, in a small number of Streptococcus mitis isolates. We have sequenced the mitilysin gene from seven isolates of S. mitis. Comparisons with the pneumococcal pneumolysin gene show 15 amino acid substitutions. S. mitis appear to release mitilysin extracellularly. Certain alleles of mitilysin are not recognized by a monoclonal antibody raised to the related toxin pneumolysin. Based on enzyme-linked immunosorbent assay ...[more]

PMID: 17071760

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Project description:Streptococcus pneumoniae (pneumococcus) is an opportunistic bacterial pathogen responsible for causing several human diseases including pneumonia, meningitis, and otitis media. Pneumococcus is also a major cause of human ocular infections and is commonly isolated in cases of bacterial keratitis, an infection of the cornea. The ocular pathology that occurs during pneumococcal keratitis is partly due to the actions of pneumolysin (Ply), a cholesterol-dependent cytolysin produced by pneumococcus. The lytic mechanism of Ply is a three step process beginning with surface binding to cholesterol. Multiple Ply monomers then oligomerize to form a prepore. The prepore then undergoes a conformational change that creates a large pore in the host cell membrane, resulting in cell lysis. We engineered a collection of single amino acid substitution mutants at residues (A370, A406, W433, and L460) that are crucial to the progression of the lytic mechanism and determined the effects that these mutations had on lytic function. Both Ply(WT) and the mutant Ply molecules (Ply(A370G), Ply(A370E), Ply(A406G), Ply(A406E), Ply(W433G), Ply(W433E), Ply(W433F), Ply(L460G), and Ply(L460E)) were able to bind to the surface of human corneal epithelial cells (HCECs) with similar efficiency. Additionally, Ply(WT) localized to cholesterol-rich microdomains on the HCEC surface, however, only one mutant (Ply(A370G)) was able to duplicate this behavior. Four of the 9 mutant Ply molecules (Ply(A370E), Ply(W433G), Ply(W433E), and Ply(L460E)) were deficient in oligomer formation. Lastly, all of the mutant Ply molecules, except Ply(A370G), exhibited significantly impaired lytic activity on HCECs. The other 8 mutants all experienced a reduction in lytic activity, but 4 of the 8 retained the ability to oligomerize. A thorough understanding of the molecular interactions that occur between Ply and the target cell, could lead to targeted treatments aimed to reduce the pathology observed during pneumococcal keratitis.

Dataset Information

Identification of a secreted cholesterol-dependent cytolysin (mitilysin) from Streptococcus mitis.

Publications

Identification of a secreted cholesterol-dependent cytolysin (mitilysin) from Streptococcus mitis.

Similar Datasets

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