Rohmer, CarinaDobritz, RonjaTuncbilek-Dere, DilekLehmann, EstherGerlach, DavidGeorge, Shilpa ElizabethBae, TaeokNieselt, KayWolz, Christiane2023-09-272023-09-272022Rohmer C, Dobritz R, Tuncbilek-Dere D, et al. Influence of Staphylococcus aureus Strain Background on Sa3int Phage Life Cycle Switches. Viruses. 2022;14(11):2471. Published 2022 Nov 8. doi:10.3390/v14112471https://hdl.handle.net/1805/35824Staphylococcus aureus asymptomatically colonizes the nasal cavity of mammals, but it is also a leading cause of life-threatening infections. Most human nasal isolates carry Sa3 phages, which integrate into the bacterial hlb gene encoding a sphingomyelinase. The virulence factor-encoding genes carried by the Sa3-phages are highly human-specific, and most animal strains are Sa3 negative. Thus, both insertion and excision of the prophage could potentially confer a fitness advantage to S. aureus. Here, we analyzed the phage life cycle of two Sa3 phages, Φ13 and ΦN315, in different phage-cured S. aureus strains. Based on phage transfer experiments, strains could be classified into low (8325-4, SH1000, and USA300c) and high (MW2c and Newman-c) transfer strains. High-transfer strains promoted the replication of phages, whereas phage adsorption, integration, excision, or recA transcription was not significantly different between strains. RNASeq analyses of replication-deficient lysogens revealed no strain-specific differences in the CI/Mor regulatory switch. However, lytic genes were significantly upregulated in the high transfer strain MW2c Φ13 compared to strain 8325-4 Φ13. By transcriptional start site prediction, new promoter regions within the lytic modules were identified, which are likely targeted by specific host factors. Such host-phage interaction probably accounts for the strain-specific differences in phage replication and transfer frequency. Thus, the genetic makeup of the host strains may determine the rate of phage mobilization, a feature that might impact the speed at which certain strains can achieve host adaptation.en-USAttribution 4.0 InternationalStaphylococcusGene regulationHemolysinInductionPhageVirulenceArticle