TheStreptococcus pyogenesM protein is involved in phenotypic resistance to phage A25 infection in presence of human serum

Abstract

Streptococcus pyogenesis responsible for mild to life-threatening infections. Bacteriophages, or phages, and their virulence genes play a key role in the emergence and expansion of epidemics. However, relatively little is known about the biology ofS. pyogenesphages, particularly in biologically relevant environments. During infection,S. pyogenesconceals from the host immune system through the binding of human serum proteins. This evasion is mediated by surface proteins, such as the M protein which is a major virulence determinant ofS. pyogenes.Here, we demonstrate that human serum proteins also confer phenotypic resistance to phage A25 infection by impeding phage adsorption. We have found that, although not directly involved in phage A25 infection, the M protein is involved in this inhibition through the binding of both IgG and albumin, especially in absence of bound fatty acids. These findings highlight the importance of studying phages within a physiological context, specifically in the environmental conditions in which they will be used.Author summaryThe issues of antimicrobial resistance and resurgence of life-threatening infection, like the recent cases of invasiveS. pyogenesinfections, are prompting the scientific community to use phages as a complementary therapy. Phages are often characterized in laboratory conditions which are very different from the infection site. During human infection,Streptococcus pyogenesuses serum proteins to protect against the immune system. Our data illustrate how the human host environment also modulates phage susceptibility ofS. pyogenes. We found that human serum transiently protects a M25 strain against infection by the lytic phage A25. This protective effect is mediated in part by the M protein, a major virulence determinant and the target of current vaccines. This new function for the M protein highlights the need to characterize bacteria-phage interactions in a more physiological context to increase the chances of success of phage therapy.