Abstract
Streptococcal peptide of virulence (SpoV) is a Streptococcus pyogenes (group A streptococcus (GAS))-specific peptide that is important for GAS survival in murine blood, and the expression of the virulence factors streptolysin O (slo) and streptolysin S (sagA). We used a spoV mutant in isolate MGAS315 to assess the contribution of the SpoV peptide to virulence by using a murine model of invasive disease and an ex vivo human model (Lancefield assay). We then used antibodies to SpoV in both models to evaluate their ability to decrease morbidity and mortality. Results showed that SpoV is essential for GAS virulence, and targeting the peptide has therapeutic potential.
Highlights
Streptococcus pyogenes (group A streptococcus (GAS)) is an exclusively human pathogen that causes both mild and invasive multiple diseases
We previously identified the streptococcal peptide of virulence (SpoV) in culture supernatants of MGAS315 when screening for GAS signaling peptides [16]
To determine if Streptococcal peptide of virulence (SpoV) is important for GAS virulence, we compared morbidity and mortality in a murine model of invasive GAS (iGAS) disease
Summary
Streptococcus pyogenes (group A streptococcus (GAS)) is an exclusively human pathogen that causes both mild and invasive multiple diseases. The diversity and severity of GAS diseases is partly attributed to the pathogens’ ability to regulate the expression of a variety of virulence factors, including adherence and invasion proteins, toxins, superantigens, proteases, and immune-modulating proteins [3]. GAS uses extracellular peptides as signaling molecules to regulate the expression of virulence genes [4,5]. Peptides are typically detected at the cell surface by a membrane-bound sensor kinase. The sensor kinase responds by transferring a phosphoryl group to a response regulator protein to change its DNA-binding specificity, which results in the activation or repression of target genes. Peptides can be actively transported into the cell, where the peptide can directly interact with a transcriptional regulator to alter target gene expression [6,7,8]
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