The prince and the pauper

EditoriaL 664 Virulence Volume 4 issue 8 It has been known in the community studying the pathogenesis of Streptococcus pyogenes that spontaneous mutation occurs during passages in laboratory media or in animals, so some of the progeny's virulence can be changed, mainly due to the change of the expression of virulence factors. Like other pathogens, S. pyogenes, a strict human pathogen, produces virulence factors to attach to and invade host tissues, avoid the immune system, or degrade or kill host tissues and cells. These virulence factors are necessary to colonize, invade, and spread in the host. However, some of these factors are not necessary to grow in laboratory media, so reduced expression of these virulence factors could increase the fitness for growth in laboratory media. A notorious S. pyogenes virulence factor whose expression changes during passages in the laboratory is M protein. M protein is a cell wall-anchored protein with a coiled-coil structure and its important role in S. pyogenes pathogenesis has long been recognized as an adhesin and antiphagocytic factor. 7 It is also the causative molecule of the streptococcal rheumatic heart disease. The antibodies generated against M protein cross react with tissues in the heart valves. 8 Thus, when S. pyogenes loses M protein, its virulence is dramatically attenuated in animal infection models. It has been a puzzle in the study of S. pyogenes whether or not the sagA/pel locus influences the expression of the M protein gene (emm). Several studies on the sagA/pel locus produced conflicting results on the regulation of M protein gene expression. However, the recent study by Zhou et al. in this issue of Virulence shows that the sagA/pel locus does not regulate the expression of M protein at least in the M1 strains that most studies for the sagA/pel locus used, and the confusion has been caused by secondary spurious mutations during mutagenesis. 9 This study by Zhou et al. reminds us of the importance of awareness of spontaneous mutation or phase variation possibilities during mutagenesis of S. pyogenes. During laboratory passages, the expression of other virulence factors such as capsule and the protease SpeB changes, 3 so this phenomenon seems not to be limited to M protein. Recent genomic studies show that genetic changes in S. pyogenes occur not only during passages in the laboratory (in vitro passage) but also during infection (in vivo passage). Interestingly, these genetic changes are selected mostly …