{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:47:57Z","timestamp":1790754477229,"version":"4.1.0"},"reference-count":49,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,8]],"date-time":"2022-11-08T00:00:00Z","timestamp":1667865600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Forschungsgemeinschaft","award":["174858087"],"award-info":[{"award-number":["174858087"]}]},{"name":"Deutsche Forschungsgemeinschaft","award":["464612409"],"award-info":[{"award-number":["464612409"]}]},{"name":"Deutsche Forschungsgemeinschaft","award":["390838134"],"award-info":[{"award-number":["390838134"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Staphylococcus 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, \u03a613 and \u03a6N315, 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 \u03a613 compared to strain 8325-4 \u03a613. 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.<\/jats:p>","DOI":"10.3390\/v14112471","type":"journal-article","created":{"date-parts":[[2022,11,8]],"date-time":"2022-11-08T10:55:32Z","timestamp":1667904932000},"page":"2471","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Influence of Staphylococcus aureus Strain Background on Sa3int Phage Life Cycle Switches"],"prefix":"10.3390","volume":"14","author":[{"given":"Carina","family":"Rohmer","sequence":"first","affiliation":[{"name":"Interfaculty Institute of Microbiology and Infection Medicine, University of T\u00fcbingen, 72074 T\u00fcbingen, Germany"},{"name":"Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, 70569 Stuttgart, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronja","family":"Dobritz","sequence":"additional","affiliation":[{"name":"Interfaculty Institute of Microbiology and Infection Medicine, University of T\u00fcbingen, 72074 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dilek","family":"Tuncbilek-Dere","sequence":"additional","affiliation":[{"name":"Cluster of Excellence EXC 2124 \u201cControlling Microbes to Fight Infections\u201d, University of T\u00fcbingen, 72074 T\u00fcbingen, Germany"},{"name":"Institute for Bioinformatics and Medical Informatics, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Lehmann","sequence":"additional","affiliation":[{"name":"Interfaculty Institute of Microbiology and Infection Medicine, University of T\u00fcbingen, 72074 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1926-0967","authenticated-orcid":false,"given":"David","family":"Gerlach","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of W\u00fcrzburg, 97074 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2782-4993","authenticated-orcid":false,"given":"Shilpa Elizabeth","family":"George","sequence":"additional","affiliation":[{"name":"Interfaculty Institute of Microbiology and Infection Medicine, University of T\u00fcbingen, 72074 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0576-2851","authenticated-orcid":false,"given":"Taeok","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Indiana University School of Medicine-Northwest, Gary, IN 46408, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1283-7065","authenticated-orcid":false,"given":"Kay","family":"Nieselt","sequence":"additional","affiliation":[{"name":"Cluster of Excellence EXC 2124 \u201cControlling Microbes to Fight Infections\u201d, University of T\u00fcbingen, 72074 T\u00fcbingen, Germany"},{"name":"Institute for Bioinformatics and Medical Informatics, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3909-5281","authenticated-orcid":false,"given":"Christiane","family":"Wolz","sequence":"additional","affiliation":[{"name":"Interfaculty Institute of Microbiology and Infection Medicine, University of T\u00fcbingen, 72074 T\u00fcbingen, Germany"},{"name":"Cluster of Excellence EXC 2124 \u201cControlling Microbes to Fight Infections\u201d, University of T\u00fcbingen, 72074 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.tim.2019.12.007","article-title":"The Evolutionary Genomics of Host Specificity in Staphylococcus aureus","volume":"28","author":"Matuszewska","year":"2020","journal-title":"Trends Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"ftx005","DOI":"10.1093\/femspd\/ftx005","article-title":"Staphylococcus aureus pathogenesis in diverse host environments","volume":"75","author":"Balasubramanian","year":"2017","journal-title":"Pathog. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/s41579-018-0147-4","article-title":"Methicillin-resistant Staphylococcus aureus: An overview of basic and clinical research","volume":"17","author":"Turner","year":"2019","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2419","DOI":"10.3389\/fmicb.2018.02419","article-title":"Staphylococcus aureus Nasal Colonization: An Update on Mechanisms, Epidemiology, Risk Factors, and Subsequent Infections","volume":"9","author":"Sakr","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Haag, A.F., Fitzgerald, J.R., and Penades, J.R. (2019). Staphylococcus aureus in Animals. Microbiol. Spectr., 7.","DOI":"10.1128\/microbiolspec.GPP3-0060-2019"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1038\/s41559-018-0617-0","article-title":"Gene exchange drives the ecological success of a multi-host bacterial pathogen","volume":"2","author":"Richardson","year":"2018","journal-title":"Nat. Ecol. Evol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6","DOI":"10.3389\/fcimb.2012.00006","article-title":"Staphylococcus aureus temperate bacteriophage: Carriage and horizontal gene transfer is lineage associated","volume":"2","author":"McCarthy","year":"2012","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Ingmer, H., Gerlach, D., and Wolz, C. (2019). Temperate Phages of Staphylococcus aureus. Microbiol. Spectr., 7.","DOI":"10.1128\/microbiolspec.GPP3-0058-2018"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Chaguza, C., Smith, J.T., Bruce, S.A., Gibson, R., Martin, I.W., and Andam, C.P. (2022). Prophage-encoded immune evasion factors are critical for Staphylococcus aureus host infection, switching, and adaptation. Cell Genom.","DOI":"10.1016\/j.xgen.2022.100194"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1159\/000516645","article-title":"The Role of hlb-Converting Bacteriophages in Staphylococcus aureus Host Adaption","volume":"31","author":"Rohmer","year":"2021","journal-title":"Microb. Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Bouiller, K., Bertrand, X., Hocquet, D., and Chirouze, C. (2020). Human Infection of Methicillin-Susceptible Staphylococcus aureus CC398: A Review. Microorganisms, 8.","DOI":"10.3390\/microorganisms8111737"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1099\/mic.0.2007\/015289-0","article-title":"Staphylococcus aureus host specificity: Comparative genomics of human versus animal isolates by multi-strain microarray","volume":"154","author":"Sung","year":"2008","journal-title":"Microbiol. Read."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3462","DOI":"10.1128\/JB.01804-08","article-title":"Diversity of prophages in dominant Staphylococcus aureus clonal lineages","volume":"191","author":"Goerke","year":"2009","journal-title":"J. Bacteriol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1128\/JB.188.4.1310-1315.2006","article-title":"The innate immune modulators staphylococcal complement inhibitor and chemotaxis inhibitory protein of Staphylococcus aureus are located on beta-hemolysin-converting bacteriophages","volume":"188","author":"Rooijakkers","year":"2006","journal-title":"J. Bacteriol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1111\/j.1365-2958.2006.05354.x","article-title":"Extensive phage dynamics in Staphylococcus aureus contributes to adaptation to the human host during infection","volume":"61","author":"Goerke","year":"2006","journal-title":"Mol. Microbiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3316","DOI":"10.3390\/v4123316","article-title":"The Staphylococci phages family: An overview","volume":"4","author":"Deghorain","year":"2012","journal-title":"Viruses"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2527","DOI":"10.1111\/j.1462-2920.2010.02226.x","article-title":"Multilocus PCR typing strategy for differentiation of Staphylococcus aureus siphoviruses reflecting their modular genome structure","volume":"12","author":"Kahankova","year":"2010","journal-title":"Environ. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Oliveira, H., Sampaio, M., Melo, L.D.R., Dias, O., Pope, W.H., Hatfull, G.F., and Azeredo, J. (2019). Staphylococci phages display vast genomic diversity and evolutionary relationships. BMC Genom., 20.","DOI":"10.1186\/s12864-019-5647-8"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Zhou, W., Wen, H., Li, Y., Gao, Y., Zheng, X., Yuan, L., Zhu, G., and Yang, Z. (2022). Whole-Genome Analysis Reveals That Bacteriophages Promote Environmental Adaptation of Staphylococcus aureus via Gene Exchange, Acquisition, and Loss. Viruses, 14.","DOI":"10.3390\/v14061199"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3491","DOI":"10.1099\/mic.0.032466-0","article-title":"Transcription of the phage-encoded Panton-Valentine leukocidin of Staphylococcus aureus is dependent on the phage life-cycle and on the host background","volume":"155","author":"Wirtz","year":"2009","journal-title":"Microbiol. Read."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1038\/s41586-018-0730-x","article-title":"Methicillin-resistant Staphylococcus aureus alters cell wall glycosylation to evade immunity","volume":"563","author":"Gerlach","year":"2018","journal-title":"Nature"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1111\/j.1365-2958.2006.05441.x","article-title":"Prophages of Staphylococcus aureus Newman and their contribution to virulence","volume":"62","author":"Bae","year":"2006","journal-title":"Mol. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Geiger, T., Francois, P., Liebeke, M., Fraunholz, M., Goerke, C., Krismer, B., Schrenzel, J., Lalk, M., and Wolz, C. (2012). The stringent response of Staphylococcus aureus and its impact on survival after phagocytosis through the induction of intracellular PSMs expression. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1003016"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e00277-11","DOI":"10.1128\/mBio.00277-11","article-title":"Transforming the untransformable: Application of direct transformation to manipulate genetically Staphylococcus aureus and Staphylococcus epidermidis","volume":"3","author":"Monk","year":"2012","journal-title":"mBio"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4006","DOI":"10.1128\/JB.01412-10","article-title":"Wall teichoic Acid-dependent adsorption of staphylococcal siphovirus and myovirus","volume":"193","author":"Xia","year":"2011","journal-title":"J. Bacteriol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1261\/rna.048470.114","article-title":"Whole-genome mapping of 5\u2018 RNA ends in bacteria by tagged sequencing: A comprehensive view in Enterococcus faecalis","volume":"21","author":"Innocenti","year":"2015","journal-title":"RNA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.ijmm.2012.01.002","article-title":"Revisiting the genomes of the Staphylococcus aureus strains NCTC 8325 and RN4220","volume":"302","author":"Berscheid","year":"2012","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3421","DOI":"10.1093\/bioinformatics\/btu533","article-title":"READemption-a tool for the computational analysis of deep-sequencing-based transcriptome data","volume":"30","author":"Forstner","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Hoffmann, S., Otto, C., Kurtz, S., Sharma, C.M., Khaitovich, P., Vogel, J., Stadler, P.F., and Hackerm\u00fcller, J. (2009). Fast mapping of short sequences with mismatches, insertions and deletions using index structures. PLoS Comput. Biol., 5.","DOI":"10.1371\/journal.pcbi.1000502"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.ymeth.2015.06.012","article-title":"Differential RNA-seq (dRNA-seq) for annotation of transcriptional start sites and small RNAs in Helicobacter pylori","volume":"86","author":"Bischler","year":"2015","journal-title":"Methods"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Dugar, G., Herbig, A., Forstner, K.U., Heidrich, N., Reinhardt, R., Nieselt, K., and Sharma, C.M. (2013). High-resolution transcriptome maps reveal strain-specific regulatory features of multiple Campylobacter jejuni isolates. PLoS Genet., 9.","DOI":"10.1371\/journal.pgen.1003495"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2418","DOI":"10.3389\/fmicb.2017.02418","article-title":"Commercial Biocides Induce Transfer of Prophage Phi13 from Human Strains of Staphylococcus aureus to Livestock CC398","volume":"8","author":"Tang","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"13333","DOI":"10.1038\/ncomms13333","article-title":"Bacterial viruses enable their host to acquire antibiotic resistance genes from neighbouring cells","volume":"7","author":"Haaber","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Moller, A.G., Lindsay, J.A., and Read, T.D. (2019). Determinants of Phage Host Range in Staphylococcus Species. Appl. Environ. Microbiol., 85.","DOI":"10.1128\/AEM.00209-19"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e1245","DOI":"10.1002\/mbo3.1245","article-title":"Characterization of the genetic switch from phage 13 important for Staphylococcus aureus colonization in humans","volume":"10","author":"Kristensen","year":"2021","journal-title":"Microbiol. Open"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1073\/pnas.1812746116","article-title":"Noncontiguous operon is a genetic organization for coordinating bacterial gene expression","volume":"116","author":"Bitarte","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"8659","DOI":"10.1038\/s41598-020-65493-0","article-title":"Repression of the lysogenic PR promoter in bacteriophage TP901-1 through binding of a CI-MOR complex to a composite OM-OR operator","volume":"10","author":"Pedersen","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"20576","DOI":"10.1073\/pnas.2005218117","article-title":"Revealing the mechanism of repressor inactivation during switching of a temperate bacteriophage","volume":"117","author":"Rasmussen","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/j.jmb.2008.09.071","article-title":"The role of MOR and the CI operator sites on the genetic switch of the temperate bacteriophage TP901-1","volume":"384","author":"Pedersen","year":"2008","journal-title":"J. Mol. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1261\/rna.073288.119","article-title":"Dynamic insights on transcription initiation and RNA processing during bacterial adaptation","volume":"26","author":"Lacoux","year":"2020","journal-title":"RNA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1111\/j.1365-2958.2012.08144.x","article-title":"RNase Y of Staphylococcus aureus and its role in the activation of virulence genes","volume":"85","author":"Marincola","year":"2012","journal-title":"Molecular Microbiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"18384","DOI":"10.1073\/pnas.1909801116","article-title":"Structural basis of Q-dependent antitermination","volume":"116","author":"Yin","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1038\/nrmicro3527","article-title":"A new perspective on lysogeny: Prophages as active regulatory switches of bacteria","volume":"13","author":"Feiner","year":"2015","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"107956","DOI":"10.1016\/j.celrep.2020.107956","article-title":"Active Lysogeny in Listeria monocytogenes is a bacteria-phage adaptive response in the mammalian environment","volume":"32","author":"Pasechnek","year":"2020","journal-title":"Cell Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4670","DOI":"10.1016\/j.jmb.2019.02.011","article-title":"Impact of xenogeneic silencing on phage-host interactions","volume":"431","author":"Pfeifer","year":"2019","journal-title":"J. Mol. Biol."},{"key":"ref_46","first-page":"593","article-title":"Phages of Staphylococcus aureus and their impact on host evolution","volume":"21","author":"Xia","year":"2014","journal-title":"Infect. Genet. Evol. J. Mol. Epidemiol. Evol. Genet. Infect. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1038\/s41564-020-0777-y","article-title":"Diversity and classification of cyclic-oligonucleotide-based anti-phage signalling systems","volume":"5","author":"Millman","year":"2020","journal-title":"Nat. Microbiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1016\/j.cell.2020.09.065","article-title":"Bacterial Retrons Function in Anti-Phage Defense","volume":"183","author":"Millman","year":"2020","journal-title":"Cell"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1086\/381502","article-title":"Increased frequency of genomic alterations in Staphylococcus aureus during chronic infection is in part due to phage mobilization","volume":"189","author":"Goerke","year":"2004","journal-title":"J. Infect. Dis."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/11\/2471\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:12:38Z","timestamp":1760145158000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/11\/2471"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,8]]},"references-count":49,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["v14112471"],"URL":"https:\/\/doi.org\/10.3390\/v14112471","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,8]]}}}