Staphylococcus aureus agr quorum sensing system and Sa3int temperate phage

Staphylococcus aureus is an opportunistic pathogen that causes severe infections in humans and animals. Most strains harbour temperate prophages that have a dual lifecycle switching between lysis and lysogeny. Common in human strains of S. aureus are members of the Sa3int phage family that encode human-specific immune evasion factors. Here, we examined the impact of the S. aureus agr quorum sensing (QS) system on the Sa3int phage, ?13. QS in S. aureus induces virulence factor production at high cell density through production and sensing of S. aureus auto-inducing peptides (AIPsa) and can be inhibited by AIPs produced by other staphylococcal species including the S. hyicus, AIPhy. We find that, compared to untreated cells, pretreatment with AIPsa, facilitated ?13 lysogenization in the exponential growth phase and reduced phage release from cells carrying the ?13 prophage. No differences in phage lysogenization and accumulation were observed in ?agrA mutant cells or in cells treated with AIPhy. Remarkably, when monitoring excision and circularization of phage DNA by quantitative PCR we found that agr does not influence excision of the phage from the bacterial genome. Transcriptomic analysis revealed that AIPsa treatment led to differential expression of a phage gene encoding a putative phage tail terminator, suggesting that agr might affect phage maturation. Our findings show that agr induction favours Sa3int phage lysogeny, establishing S. aureus QS as a key regulator of prophage lifecycles.