Functional analysis of Streptococcus pyogenes nuclease A (SpnA), a novel group A streptococcal virulence factor

Streptococcus pyogenes nuclease A (SpnA) is a recently discovered DNase that plays a role in virulence as shown in a mouse infection model. SpnA is the only cell wall-anchored DNase found in S. pyogenes thus far and shows a unique protein architecture. The C-terminal nuclease domain contains highly...

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Published inMolecular microbiology Vol. 79; no. 6; pp. 1629 - 1642
Main Authors Chang, Ann, Khemlani, Adrina, Kang, HaeJoo, Proft, Thomas
Format Journal Article
LanguageEnglish
Published Oxford, UK Blackwell Publishing Ltd 01.03.2011
Blackwell
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Summary:Streptococcus pyogenes nuclease A (SpnA) is a recently discovered DNase that plays a role in virulence as shown in a mouse infection model. SpnA is the only cell wall-anchored DNase found in S. pyogenes thus far and shows a unique protein architecture. The C-terminal nuclease domain contains highly conserved catalytic site and Mg²⁺ binding site residues. However, expression of the SpnA nuclease domain alone resulted in a soluble, but enzymatically inactive protein. We found that at least two out of three oligonucleotide/oligosaccharide-binding fold motifs found in the N-terminal domain are required for SpnA activity, probably contributing to substrate binding. Using a combination of a spnA deletion mutant and a Lactococcus lactis‘gain-of-function' mutant, we have shown that SpnA promotes survival in whole human blood and in neutrophil killing assays and this is, at least in part, achieved by the destruction of neutrophil extracellular traps (NETs). We observed higher frequencies for anti-SpnA antibodies in streptococcal disease patient sera (79%, n = 19) compared with sera from healthy donors (33%, n = 9) suggesting that SpnA is expressed during infection. Detection of anti-SpnA antibodies in patient serum might be useful for the diagnostic of post-streptococcal diseases, such as acute rheumatic fever or glomerulonephritis.
Bibliography:http://dx.doi.org/10.1111/j.1365-2958.2011.07550.x
Present address: Division of Molecular Biosciences, Membrane Protein Crystallography Group, Imperial College London, UK.
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ISSN:0950-382X
1365-2958
DOI:10.1111/j.1365-2958.2011.07550.x