Characterising the interaction of the genetically diverse M-related protein from Streptococcus pyogenes with human serum proteins

<p dir="ltr"><i>Streptococcus pyogenes </i>(Group A <i>Streptococcus</i>; GAS) is a Gram-positive human pathogen, that colonises epithelial and mucosal surfaces. GAS is causative of superficial infections that resolve quickly, but it is also responsible for severe invasive diseases and post-infection sequelae that are estimated to cause over 500,000 deaths per year. In over 100 years of research, there have been numerous unsuccessful attempts to develop a vaccine against GAS. The most promising candidate to date, the 30-valent vaccine, has reached phase II clinical trials, and it relies on the M protein; an α-helical, coiled-coil, fibrillar protein that extends approximately 60 nm from the cell surface of GAS. The M protein (M) belongs to the M protein family, which also includes the cell surface expressed M-related protein (Mrp) and M-like Protein (Enn). These proteins are encoded by three adjacent genes located within the <i>mga </i>regulon known as <i>emm</i>, <i>mrp, </i>and <i>enn</i>, respectively. Recent studies have identified that the inclusion of N-terminal Mrp peptides, broadens the coverage of the M protein based 30-valent vaccine, particularly against circulating <i>emm </i>types in regions of endemic infection. To further the development of these vaccines, a deeper understanding of the role of Mrp in GAS virulence is essential. Mrp4 from the SP4 GAS strain has been shown to contribute to GAS virulence through the recruitment of Fg and IgG. Recent studies have investigated the diversity of Mrp, via analysis of the Mrp amino acid sequences from 1668 GAS genomes. The average sequence identity of Mrp was identified as 83.5% and it was concluded that Mrp could be classified into four main phylogenetic clusters based upon a 90% amino acid sequence identity. This study aimed to characterise Fg and IgG-binding by diverse Mrp.</p>