{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T19:48:04Z","timestamp":1792180084989,"version":"4.4.0"},"reference-count":64,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T00:00:00Z","timestamp":1744588800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Royal College of Surgeons of England","award":["Dr Shapurji H Modi Memorial Research Fellowship"],"award-info":[{"award-number":["Dr Shapurji H Modi Memorial Research Fellowship"]}]},{"name":"Royal College of Surgeons of England","award":["SPPG\/21\/158"],"award-info":[{"award-number":["SPPG\/21\/158"]}]},{"name":"Royal College of Surgeons of England","award":["British Rhinological Society research grant"],"award-info":[{"award-number":["British Rhinological Society research grant"]}]},{"DOI":"10.13039\/501100000692","name":"Royal College of Surgeons Edinburgh","doi-asserted-by":"publisher","award":["Dr Shapurji H Modi Memorial Research Fellowship"],"award-info":[{"award-number":["Dr Shapurji H Modi Memorial Research Fellowship"]}],"id":[{"id":"10.13039\/501100000692","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000692","name":"Royal College of Surgeons Edinburgh","doi-asserted-by":"publisher","award":["SPPG\/21\/158"],"award-info":[{"award-number":["SPPG\/21\/158"]}],"id":[{"id":"10.13039\/501100000692","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000692","name":"Royal College of Surgeons Edinburgh","doi-asserted-by":"publisher","award":["British Rhinological Society research grant"],"award-info":[{"award-number":["British Rhinological Society research grant"]}],"id":[{"id":"10.13039\/501100000692","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Staphylococcus aureus (S. aureus) colonizes the nasal cavities of both healthy individuals and patients with chronic rhinosinusitis (CRS) with (CRSwNP) and without (CRSsNP) nasal polyps. Treatment-resistant S. aureus biofilms and intracellular persistence are common in CRS patients, requiring the expression of specific virulence factor genes to transition into these forms. We hypothesized that S. aureus isolates from non-diseased controls, CRSsNP patients, and CRSwNP patients would exhibit distinct virulence factor patterns contributing to persistence and intracellular survival in CRS patients. Nasal swabs from seventy-seven individuals yielded S. aureus cultures in eight non-diseased controls, eight CRSsNP patients, and five CRSwNP patients. Whole-genome sequencing analyzed stress, antimicrobial resistance, and virulence genes, including plasmids and prophages. Four virulence factor gene patterns emerged: a core set (hlgA, icaC, hlgB, hlgC, hld, and aur) present in all isolates, and accessory sets, including the enterotoxin gene cluster (seo, sem, seu, sei, and sen) and a partial\/complete invasive virulence factor set (splE, splA, splB, lukE, and lukD) (p = 0.001). CRSwNP isolates exhibited incomplete carriage of the core set, with frequent loss of scn, icaC, and hlgA (p &lt; 0.05). These findings suggest that S. aureus has clusters of virulence factors that may act in concert to support the survival and persistence of the bacteria, resulting in enhanced pathogenicity. This may manifest clinically with resistant disease and refractoriness to antibiotics.<\/jats:p>","DOI":"10.3390\/ijms26083711","type":"journal-article","created":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T03:59:06Z","timestamp":1744689546000},"page":"3711","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Identification of Novel Staphylococcus aureus Core and Accessory Virulence Patterns in Chronic Rhinosinusitis"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3912-9026","authenticated-orcid":false,"given":"Simon P.","family":"Goldie","sequence":"first","affiliation":[{"name":"School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK"},{"name":"Department of Otorhinolaryngology\/Head & Neck Surgery, University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurie C.","family":"Lau","sequence":"additional","affiliation":[{"name":"School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huw A. S.","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\/Head & Neck Surgery, University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip G.","family":"Harries","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\/Head & Neck Surgery, University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew F.","family":"Walls","sequence":"additional","affiliation":[{"name":"School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6753-7844","authenticated-orcid":false,"given":"Rami J.","family":"Salib","sequence":"additional","affiliation":[{"name":"School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK"},{"name":"Department of Otorhinolaryngology\/Head & Neck Surgery, University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1086\/345476","article-title":"Comparison of mortality associated with methicillin-resistant and methicillin-susceptible Staphylococcus aureus bacteremia: A meta-analysis","volume":"36","author":"Cosgrove","year":"2003","journal-title":"Clin. Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s11882-019-0853-7","article-title":"The Role of Staphylococcus aureus in Patients with Chronic Sinusitis and Nasal Polyposis","volume":"19","author":"Vickery","year":"2019","journal-title":"Curr. Allergy Asthma Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1016\/j.jaci.2004.07.013","article-title":"Staphylococcus aureus colonization and IgE antibody formation to enterotoxins is increased in nasal polyposis","volume":"114","author":"Gevaert","year":"2004","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.3892\/etm.2015.2247","article-title":"Serum levels of specific IgE to Staphylococcus aureus enterotoxins in patients with chronic rhinosinusitis","volume":"9","author":"Cui","year":"2015","journal-title":"Exp. Ther. Med."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Maniakas, A., Asmar, M.H., Renteria Flores, A.E., Nayan, S., Alromaih, S., Mfuna Endam, L., and Desrosiers, M.Y. (2018). Staphylococcus aureus on Sinus Culture Is Associated With Recurrence of Chronic Rhinosinusitis After Endoscopic Sinus Surgery. Front. Cell Infect. Microbiol., 8.","DOI":"10.3389\/fcimb.2018.00150"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/bs.aambs.2020.05.001","article-title":"Evasion of host defenses by intracellular Staphylococcus aureus","volume":"112","author":"Watkins","year":"2020","journal-title":"Adv. Appl. Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1002\/alr.21154","article-title":"Intracellular Staphylococcus aureus: The Trojan horse of recalcitrant chronic rhinosinusitis?","volume":"3","author":"Tan","year":"2013","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1002\/lary.21805","article-title":"Staphylococcus aureus biofilms: Nemesis of endoscopic sinus surgery","volume":"121","author":"Singhal","year":"2011","journal-title":"Laryngoscope"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1016\/j.jaci.2014.12.1929","article-title":"Intracellular residency of Staphylococcus aureus within mast cells in nasal polyps: A novel observation","volume":"135","author":"Hayes","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/nrmicro3161","article-title":"Adhesion, invasion and evasion: The many functions of the surface proteins of Staphylococcus aureus","volume":"12","author":"Foster","year":"2014","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Shaghayegh, G., Cooksley, C., Ramezanpour, M., Wormald, P.J., Psaltis, A.J., and Vreugde, S. (2022). Chronic Rhinosinusitis, S. aureus Biofilm and Secreted Products, Inflammatory Responses, and Disease Severity. Biomedicines, 10.","DOI":"10.3390\/biomedicines10061362"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1111\/mmi.13634","article-title":"Staphylococcus aureus biofilm: A complex developmental organism","volume":"104","author":"Moormeier","year":"2017","journal-title":"Mol. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.ijmm.2013.11.011","article-title":"Staphylococcus aureus persistence in non-professional phagocytes","volume":"304","author":"Loffler","year":"2014","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Oliveira, D., Borges, A., and Simoes, M. (2018). Staphylococcus aureus Toxins and Their Molecular Activity in Infectious Diseases. Toxins, 10.","DOI":"10.3390\/toxins10060252"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.mib.2013.01.012","article-title":"The effects of Staphylococcus aureus leukotoxins on the host: Cell lysis and beyond","volume":"16","author":"Yoong","year":"2013","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1111\/j.1348-0421.2003.tb02789.x","article-title":"Purification, cloning and characterization of variant LukE-LukD with strong leukocidal activity of staphylococcal bi-component leukotoxin family","volume":"47","author":"Morinaga","year":"2003","journal-title":"Microbiol. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1038\/nrmicro3110","article-title":"Phenol-soluble modulins and staphylococcal infection","volume":"11","author":"Peschel","year":"2013","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.ijmm.2013.11.019","article-title":"Phenol-soluble modulins","volume":"304","author":"Otto","year":"2014","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.1111\/j.1365-2222.2007.02838.x","article-title":"Local immunoglobulin production in nasal polyposis is modulated by superantigens","volume":"37","author":"Gevaert","year":"2007","journal-title":"Clin. Exp. Allergy"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.jaci.2019.06.013","article-title":"Staphylococcus aureus internalization in mast cells in nasal polyps: Characterization of interactions and potential mechanisms","volume":"145","author":"Hayes","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Tan, L., Huang, Y., Shang, W., Yang, Y., Peng, H., Hu, Z., Wang, Y., Rao, Y., Hu, Q., and Rao, X. (2022). Accessory Gene Regulator (agr) Allelic Variants in Cognate Staphylococcus aureus Strain Display Similar Phenotypes. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.700894"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4213","DOI":"10.1128\/JCM.05290-11","article-title":"Age- and gender-associated Staphylococcus aureus spa types found among nasal carriers in a general population: The Tromso Staph and Skin Study","volume":"49","author":"Sangvik","year":"2011","journal-title":"J. Clin. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Bonnet, I., Millon, B., Meugnier, H., Vandenesch, F., Maurin, M., Pavese, P., and Boisset, S. (2018). High prevalence of spa type t571 among methicillin-susceptible Staphylococcus aureus from bacteremic patients in a French University Hospital. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0204977"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"7341","DOI":"10.1128\/JB.183.24.7341-7353.2001","article-title":"Transcription profiling-based identification of Staphylococcus aureus genes regulated by the agr and\/or sarA loci","volume":"183","author":"Dunman","year":"2001","journal-title":"J. Bacteriol."},{"key":"ref_25","first-page":"000726","article-title":"Prophages encoding human immune evasion cluster genes are enriched in Staphylococcus aureus isolated from chronic rhinosinusitis patients with nasal polyps","volume":"7","author":"Nepal","year":"2021","journal-title":"Microb. Genom."},{"key":"ref_26","first-page":"001128","article-title":"The intra-host evolutionary landscape and pathoadaptation of persistent Staphylococcus aureus in chronic rhinosinusitis","volume":"9","author":"Houtak","year":"2023","journal-title":"Microb. Genom."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/mSystems.00190-20","article-title":"Bactopia: A Flexible Pipeline for Complete Analysis of Bacterial Genomes","volume":"5","author":"Petit","year":"2020","journal-title":"mSystems"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1186\/s12931-018-0823-y","article-title":"Prevalence of asthma, aspirin sensitivity and allergy in chronic rhinosinusitis: Data from the UK National Chronic Rhinosinusitis Epidemiology Study","volume":"19","author":"Philpott","year":"2018","journal-title":"Respir. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1111\/j.1398-9995.2011.02709.x","article-title":"Asthma in adults and its association with chronic rhinosinusitis: The GA2LEN survey in Europe","volume":"67","author":"Jarvis","year":"2012","journal-title":"Allergy"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4193\/Rhin20.401","article-title":"European Position Paper on Rhinosinusitis and Nasal Polyps 2020","volume":"58","author":"Fokkens","year":"2020","journal-title":"Rhinology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.otohns.2007.02.004","article-title":"The Lund-Mackay staging system for chronic rhinosinusitis: How is it used and what does it predict?","volume":"137","author":"Hopkins","year":"2007","journal-title":"Otolaryngol. Head. Neck Surg."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1177\/0194599817717960","article-title":"Reversal of Smoking Effects on Chronic Rhinosinusitis after Smoking Cessation","volume":"157","author":"Phillips","year":"2017","journal-title":"Otolaryngol. Head. Neck Surg."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1002\/alr.22425","article-title":"Detection and quantification of Staphylococcus in chronic rhinosinusitis","volume":"9","author":"Baker","year":"2019","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1002\/lary.21024","article-title":"Different biofilms, different disease? A clinical outcomes study","volume":"120","author":"Foreman","year":"2010","journal-title":"Laryngoscope"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1128\/JCM.41.1.456-459.2003","article-title":"Prevalence of agr specificity groups among Staphylococcus aureus strains colonizing children and their guardians","volume":"41","author":"Shopsin","year":"2003","journal-title":"J. Clin. Microbiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6517","DOI":"10.1128\/JB.182.22.6517-6522.2000","article-title":"Exfoliatin-producing strains define a fourth agr specificity group in Staphylococcus aureus","volume":"182","author":"Jarraud","year":"2000","journal-title":"J. Bacteriol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1002\/j.1460-2075.1990.tb08254.x","article-title":"The role of the delta-lysin gene (hld) in the regulation of virulence genes by the accessory gene regulator (agr) in Staphylococcus aureus","volume":"9","author":"Janzon","year":"1990","journal-title":"EMBO J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2387","DOI":"10.1021\/bi051992u","article-title":"Glycerol monolaurate inhibits the effects of Gram-positive select agents on eukaryotic cells","volume":"45","author":"Peterson","year":"2006","journal-title":"Biochemistry"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1111\/j.1462-5822.2005.00533.x","article-title":"Multiple virulence factors are required for Staphylococcus aureus-induced apoptosis in endothelial cells","volume":"7","author":"Kahl","year":"2005","journal-title":"Cell Microbiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.tim.2008.11.004","article-title":"Staphylococcus aureus as an intracellular pathogen: The role of small colony variants","volume":"17","author":"Sendi","year":"2009","journal-title":"Trends Microbiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1086\/317606","article-title":"Impact of the agr quorum-sensing system on adherence to polystyrene in Staphylococcus aureus","volume":"182","author":"Vuong","year":"2000","journal-title":"J. Infect. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Bardy, J.J., Sarovich, D.S., Price, E.P., Steinig, E., Tong, S., Drilling, A., Ou, J., Vreugde, S., Wormald, P.J., and Psaltis, A.J. (2018). Staphylococcus aureus from patients with chronic rhinosinusitis show minimal genetic association between polyp and non-polyp phenotypes. BMC Ear Nose Throat Disord., 18.","DOI":"10.1186\/s12901-018-0064-1"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.toxicon.2021.08.007","article-title":"Bi-component HlgC\/HlgB and HlgA\/HlgB gamma-hemolysins from S. aureus: Modulation of Ca(2+) channels activity through a differential mechanism","volume":"201","author":"Staali","year":"2021","journal-title":"Toxicon"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"6445","DOI":"10.4049\/jimmunol.1002948","article-title":"Staphylococcus aureus metalloprotease aureolysin cleaves complement C3 to mediate immune evasion","volume":"186","author":"Laarman","year":"2011","journal-title":"J. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1016\/j.febslet.2014.04.002","article-title":"A different path: Revealing the function of staphylococcal proteins in biofilm formation","volume":"588","author":"Atkin","year":"2014","journal-title":"FEBS Lett."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Sedarat, Z., and Taylor-Robinson, A.W. (2022). Biofilm Formation by Pathogenic Bacteria: Applying a Staphylococcus aureus Model to Appraise Potential Targets for Therapeutic Intervention. Pathogens, 11.","DOI":"10.3390\/pathogens11040388"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1111\/j.1365-2958.2011.07942.x","article-title":"Staphylococcus aureus leucocidin ED contributes to systemic infection by targeting neutrophils and promoting bacterial growth in vivo","volume":"83","author":"Alonzo","year":"2012","journal-title":"Mol. Microbiol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Dasari, P., Nordengrun, M., Vilhena, C., Steil, L., Abdurrahman, G., Surmann, K., Dhople, V., Lahrberg, J., Bachert, C., and Skerka, C. (2022). The Protease SplB of Staphylococcus aureus Targets Host Complement Components and Inhibits Complement-Mediated Bacterial Opsonophagocytosis. J. Bacteriol., 204.","DOI":"10.1128\/JB.00184-21"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Fischer, A.J., Kilgore, S.H., Singh, S.B., Allen, P.D., Hansen, A.R., Limoli, D.H., and Schlievert, P.M. (2019). High Prevalence of Staphylococcus aureus Enterotoxin Gene Cluster Superantigens in Cystic Fibrosis Clinical Isolates. Genes, 10.","DOI":"10.3390\/genes10121036"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Song, L., Florea, L., and Langmead, B. (2014). Lighter: Fast and memory-efficient sequencing error correction without counting. Genome Biol., 15.","DOI":"10.1186\/s13059-014-0509-9"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"i884","DOI":"10.1093\/bioinformatics\/bty560","article-title":"fastp: An ultra-fast all-in-one FASTQ preprocessor","volume":"34","author":"Chen","year":"2018","journal-title":"Bioinformatics"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1093\/bioinformatics\/btu153","article-title":"Prokka: Rapid prokaryotic genome annotation","volume":"30","author":"Seemann","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_53","first-page":"000685","article-title":"Bakta: Rapid and standardized annotation of bacterial genomes via alignment-free sequence identification","volume":"7","author":"Schwengers","year":"2021","journal-title":"Microb. Genom."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"5442","DOI":"10.1128\/JCM.41.12.5442-5448.2003","article-title":"Typing of methicillin-resistant Staphylococcus aureus in a university hospital setting by using novel software for spa repeat determination and database management","volume":"41","author":"Harmsen","year":"2003","journal-title":"J. Clin. Microbiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1093\/bib\/bbs017","article-title":"Integrative Genomics Viewer (IGV): High-performance genomics data visualization and exploration","volume":"14","author":"Thorvaldsdottir","year":"2013","journal-title":"Brief. Bioinform."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/AAC.00483-19","article-title":"Validating the AMRFinder Tool and Resistance Gene Database by Using Antimicrobial Resistance Genotype-Phenotype Correlations in a Collection of Isolates","volume":"63","author":"Feldgarden","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_57","unstructured":"R Core Team (2023). R: A Language and Environment for Statistical Computing, R Foundation For Statistical Computing."},{"key":"ref_58","unstructured":"Kolde, R. (2018). Pheatmap: Pretty Heatmaps, Github. R package version 1.0.12."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Krijthe, J.H. (2015). T-Distributed Stochastic Neighbor Embedding Using a Barnes-Hut Implementation, Github Leiden University. R package version 0.17.","DOI":"10.32614\/CRAN.package.Rtsne"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Wickham, H. (2016). Ggplot2, Springer Science + Business Media, LLC.","DOI":"10.1007\/978-3-319-24277-4"},{"key":"ref_61","unstructured":"Oksanen, J.S.G., Blanchet, F., Kindt, R., Legendre, P., Minchin, P., O\u2019Hara, R.S.P., Stevens, M., Szoecs, E., Wagner, H., and Barbour, M. (2024). Vegan: Community Ecology Package, CRAN University of Oulu. R package version 2.6-10."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Robertson, J., and Nash, J.H.E. (2018). MOB-suite: Software tools for clustering, reconstruction and typing of plasmids from draft assemblies. Microb. Genom., 4.","DOI":"10.1099\/mgen.0.000206"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Robertson, J., Bessonov, K., Schonfeld, J., and Nash, J.H.E. (2020). Universal whole-sequence-based plasmid typing and its utility to prediction of host range and epidemiological surveillance. Microb. Genom., 6.","DOI":"10.1099\/mgen.0.000435"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Akhter, S., Aziz, R.K., and Edwards, R.A. (2012). PhiSpy: A novel algorithm for finding prophages in bacterial genomes that combines similarity- and composition-based strategies. Nucleic Acids Res., 40.","DOI":"10.1093\/nar\/gks406"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/8\/3711\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:14:31Z","timestamp":1760030071000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/8\/3711"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,14]]},"references-count":64,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["ijms26083711"],"URL":"https:\/\/doi.org\/10.3390\/ijms26083711","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,14]]}}}