Schiavolin, L.; Steinmetz, J.; Botquin, G.; Delforge, V.; Lakhloufi, D.; Smeesters, P. R.; Botteaux, A.

Streptococcus pyogenes is 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 of S. pyogenes phages, particularly in biologically relevant environments. During infection, S. pyogenes conceals 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 of S. 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.