Molecular mechanism of quorum sensing inhibition in Streptococcus by the phage protein paratox

Abstract

Streptococcus pyogenes, or Group A Streptococcus, is a Gram-positive bacterium that 4 can be both a human commensal and pathogen. Central to this dichotomy are temperate 5 bacteriophages that incorporate into the bacterial genome as a prophage. These genetic 6 elements encode both the phage proteins as well as toxins harmful to the human host. 7 One such conserved phage protein paratox (Prx) is always found encoded adjacent to 8 the toxin genes and this linkage is preserved during transduction. Within Streptococcus 9 pyogenes, Prx functions to inhibit the quorum-sensing ComRS receptor-signal pair that is 10 the master regulator of natural competence, or the ability to uptake endogenous DNA. 11 Specifically, Prx directly binds and inhibits the receptor ComR by unknown mechanism. 12 To understand how Prx inhibits ComR at the molecular level we pursued an X-ray crystal 13 structure of Prx bound to ComR. T