{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T16:51:17Z","timestamp":1780851077010,"version":"3.54.1"},"reference-count":38,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T00:00:00Z","timestamp":1750809600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Taipei Tzu Chi Hospital","award":["TCRD-TPE-NSTC-113-18"],"award-info":[{"award-number":["TCRD-TPE-NSTC-113-18"]}]},{"name":"Taipei Tzu Chi Hospital","award":["TCRD-TPE-114-04(1\/3)"],"award-info":[{"award-number":["TCRD-TPE-114-04(1\/3)"]}]},{"name":"Taipei Tzu Chi Hospital","award":["NSTC 113-2320-B-303-006"],"award-info":[{"award-number":["NSTC 113-2320-B-303-006"]}]},{"name":"Buddhist Tzu Chi Medical Foundation","award":["TCRD-TPE-NSTC-113-18"],"award-info":[{"award-number":["TCRD-TPE-NSTC-113-18"]}]},{"name":"Buddhist Tzu Chi Medical Foundation","award":["TCRD-TPE-114-04(1\/3)"],"award-info":[{"award-number":["TCRD-TPE-114-04(1\/3)"]}]},{"name":"Buddhist Tzu Chi Medical Foundation","award":["NSTC 113-2320-B-303-006"],"award-info":[{"award-number":["NSTC 113-2320-B-303-006"]}]},{"name":"National Science and Technology Council, Taiwan","award":["TCRD-TPE-NSTC-113-18"],"award-info":[{"award-number":["TCRD-TPE-NSTC-113-18"]}]},{"name":"National Science and Technology Council, Taiwan","award":["TCRD-TPE-114-04(1\/3)"],"award-info":[{"award-number":["TCRD-TPE-114-04(1\/3)"]}]},{"name":"National Science and Technology Council, Taiwan","award":["NSTC 113-2320-B-303-006"],"award-info":[{"award-number":["NSTC 113-2320-B-303-006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Staphylococcus lugdunensis is a coagulase-negative staphylococcus known for its significant pathogenic potential, often causing severe infections such as endocarditis and bacteremia, with virulence comparable to S. aureus. Despite general susceptibility to most antibiotics, the emergence of oxacillin-resistant strains is increasingly concerning. This study conducted whole-genome sequencing on 20 S. lugdunensis isolates from Chang Gung Memorial Hospital to explore their genetic diversity, antimicrobial resistance mechanisms, and mobile genetic elements. The lugdunin biosynthetic operon, essential for antimicrobial peptide production, was present in multilocus sequence typing (MLST) types 1, 3, and 6 but absent in STs 4, 27, and 29. Additionally, IS256 insertion elements, ranging from 7 to 17 copies, were identified in four strains and linked to multidrug resistance. CRISPR-Cas systems varied across STs, with type III-A predominant in ST1 and ST6 and type IIC in ST4, ST27, and ST29; notably, ST3 lacked CRISPR systems, correlating with a higher diversity of SCCmec elements and an increased potential for horizontal gene transfer. Phage analysis revealed stable phage\u2013host associations in ST1, ST6, and ST29, whereas ST4 displayed a varied prophage profile. Phenotypic resistance profiles generally aligned with genomic predictions, although discrepancies were observed for aminoglycosides and clindamycin. These findings highlight the complex genetic landscape and evolutionary dynamics of S. lugdunensis, emphasizing the need for genomic surveillance to inform clinical management and prevent the spread of resistant strains.<\/jats:p>","DOI":"10.3390\/ijms26136106","type":"journal-article","created":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T06:55:13Z","timestamp":1750920913000},"page":"6106","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Study of lug Operon, SCCmec Elements, Antimicrobial Resistance, MGEs, and STs of Staphylococcus lugdunensis Clinical Isolates Through Whole-Genome Sequencing"],"prefix":"10.3390","volume":"26","author":[{"given":"Tein-Yao","family":"Chang","sequence":"first","affiliation":[{"name":"Institute of Preventive Medicine, National Defense Medical Center, New Taipei City 114, Taiwan"},{"name":"Graduate Institute of Pathology and Parasitology, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5858-6214","authenticated-orcid":false,"given":"Lee-Chung","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8782-3912","authenticated-orcid":false,"given":"Cheng-Yen","family":"Kao","sequence":"additional","affiliation":[{"name":"Institute of Microbiology and Immunology, National Yang Ming Chiao Tung University, Taipei 112, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1692-1707","authenticated-orcid":false,"given":"Jang-Jih","family":"Lu","sequence":"additional","affiliation":[{"name":"Division of Clinical Pathology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3167","DOI":"10.1128\/JCM.00846-17","article-title":"Is Staphylococcus lugdunensis Significant in Clinical Samples?","volume":"55","author":"Argemi","year":"2017","journal-title":"J. Clin. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e00205-20","DOI":"10.1128\/CMR.00205-20","article-title":"Staphylococcus lugdunensis: A Skin Commensal with Invasive Pathogenic Potential","volume":"34","author":"Heilbronner","year":"2021","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.jinf.2016.10.003","article-title":"The occurrence of infective endocarditis with Staphylococcus lugdunensis bacteremia: A retrospective cohort study and systematic review","volume":"74","author":"Non","year":"2017","journal-title":"J. Infect."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Chang, S.C., Kao, C.Y., Lin, L.C., Hidrosollo, J.H., and Lu, J.J. (2023). Lugdunin production and activity in Staphylococcus lugdunensis isolates are associated with its genotypes. Microbiol. Spectr., 11.","DOI":"10.1128\/spectrum.01298-23"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3140","DOI":"10.1073\/pnas.95.6.3140","article-title":"Multilocus sequence typing: A portable approach to the identification of clones within populations of pathogenic microorganisms","volume":"95","author":"Maiden","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.ijid.2015.05.022","article-title":"Persistence of a major endemic clone of oxacillin-resistant Staphylococcus lugdunensis sequence type 6 at a tertiary medical centre in northern Taiwan","volume":"36","author":"Cheng","year":"2015","journal-title":"Int. J. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3258","DOI":"10.1093\/jac\/dkx291","article-title":"Characterization of two novel variants of staphylococcal cassette chromosome mec elements in oxacillin-resistant Staphylococcus lugdunensis","volume":"72","author":"Chang","year":"2017","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Shibuya, R., Uehara, Y., Baba, T., Teruya, K., Satou, K., Hirano, T., Kirikae, T., and Hiramatsu, K. (2020). Complete genome sequence of a methicillin-resistant Staphylococcus lugdunensis strain and characteristics of its staphylococcal cassette chromosome mec. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-65632-7"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Montelongo, C., Mores, C.R., Putonti, C., Wolfe, A.J., and Abouelfetouh, A. (2022). Whole-Genome Sequencing of Staphylococcus aureus and Staphylococcus haemolyticus Clinical Isolates from Egypt. Microbiol. Spectr., 10.","DOI":"10.1128\/spectrum.02413-21"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1128\/CMR.00016-17","article-title":"Whole-Genome Sequencing of Bacterial Pathogens: The Future of Nosocomial Outbreak Analysis","volume":"30","author":"Quainoo","year":"2017","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Chang, S.C., Lin, L.C., and Lu, J.J. (2021). Comparative Genomic Analyses Reveal Potential Factors Responsible for the ST6 Oxacillin-Resistant Staphylococcus lugdunensis Endemic in a Hospital. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.765437"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2162","DOI":"10.1093\/jac\/dkz189","article-title":"Characterization of a novel, type II staphylococcal cassette chromosome mec element from an endemic oxacillin-resistant Staphylococcus lugdunensis clone in a hospital setting","volume":"74","author":"Chang","year":"2019","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Santos, I.N.M., Kurihara, M.N.L., Santos, F.F., Valiatti, T.B., Silva, J., Pignatari, A.C.C., and Salles, M.J. (2022). Comparative Phenotypic and Genomic Features of Staphylococci from Sonication Fluid of Orthopedic Implant-Associated Infections with Poor Outcome. Microorganisms, 10.","DOI":"10.3390\/microorganisms10061149"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2730","DOI":"10.1038\/s41467-019-10646-7","article-title":"Lugdunin amplifies innate immune responses in the skin in synergy with host- and microbiota-derived factors","volume":"10","author":"Bitschar","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/nature18634","article-title":"Human commensals producing a novel antibiotic impair pathogen colonization","volume":"535","author":"Zipperer","year":"2016","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1128\/IAI.72.2.1210-1215.2004","article-title":"The bacterial insertion sequence element IS256 occurs preferentially in nosocomial Staphylococcus epidermidis isolates: Association with biofilm formation and resistance to aminoglycosides","volume":"72","author":"Kozitskaya","year":"2004","journal-title":"Infect. Immun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.ijantimicag.2008.02.009","article-title":"Higher biofilm formation in multidrug-resistant clinical isolates of Staphylococcus aureus","volume":"32","author":"Kwon","year":"2008","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"10-1128","DOI":"10.1128\/AAC.01734-20","article-title":"Secretion of and Self-Resistance to the Novel Fibupeptide Antimicrobial Lugdunin by Distinct ABC Transporters in Staphylococcus lugdunensis","volume":"65","author":"Krauss","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3468","DOI":"10.1021\/cr0503097","article-title":"Assembly-line enzymology for polyketide and nonribosomal Peptide antibiotics: Logic, machinery, and mechanisms","volume":"106","author":"Fischbach","year":"2006","journal-title":"Chem. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1097\/CM9.0000000000002430","article-title":"Characteristics of staphylococcal cassette chromosome mec and lugdunin operon genes in the complete genome of Staphylococcus lugdunensis","volume":"136","author":"Fu","year":"2023","journal-title":"Chin. Med. J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"9234","DOI":"10.1002\/anie.201901589","article-title":"Synthetic Lugdunin Analogues Reveal Essential Structural Motifs for Antimicrobial Action and Proton Translocation Capability","volume":"58","author":"Schilling","year":"2019","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e568","DOI":"10.1093\/infdis\/jiae096","article-title":"A Comparative Phenotypic and Genomic Analysis of Methicillin-Resistant Staphylococcus aureus ST45 Isolates From Cellulitis and Osteomyelitis in Taiwan","volume":"230","author":"Peng","year":"2024","journal-title":"J. Infect. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Mikkelsen, K., Bowring, J.Z., Ng, Y.K., Svanberg Frisinger, F., Maglegaard, J.K., Li, Q., Sieber, R.N., Petersen, A., Andersen, P.S., and Rostol, J.T. (2023). An Endogenous Staphylococcus aureus CRISPR-Cas System Limits Phage Proliferation and Is Efficiently Excised from the Genome as Part of the SCCmec Cassette. Microbiol. Spectr., 11.","DOI":"10.1128\/spectrum.01277-23"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Kao, C.Y., Lu, J.J., Lin, L.C., Lin, H.C., and Chang, S.C. (2021). Phylogenetic Distribution of CRISPR-Cas Systems in Staphylococcus lugdunensis. Microbiol. Spectr., 9.","DOI":"10.1128\/spectrum.01247-21"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2812","DOI":"10.1093\/gbe\/evx192","article-title":"Mobile Genetic Elements and Evolution of CRISPR-Cas Systems: All the Way There and Back","volume":"9","author":"Koonin","year":"2017","journal-title":"Genome Biol. Evol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3003","DOI":"10.1128\/JCM.00988-12","article-title":"Multilocus sequence typing analysis of Staphylococcus lugdunensis implies a clonal population structure","volume":"50","author":"Chassain","year":"2012","journal-title":"J. Clin. Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Argemi, X., Matelska, D., Ginalski, K., Riegel, P., Hansmann, Y., Bloom, J., Pestel-Caron, M., Dahyot, S., Lebeurre, J., and Prevost, G. (2018). Comparative genomic analysis of Staphylococcus lugdunensis shows a closed pan-genome and multiple barriers to horizontal gene transfer. BMC Genom., 19.","DOI":"10.1186\/s12864-018-4978-1"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1007\/s10123-024-00577-9","article-title":"Genomic analysis of multi-drug resistant coagulase-negative staphylococci from healthy humans and animals revealed unusual mechanisms of resistance and CRISPR-Cas system","volume":"28","author":"Abdullahi","year":"2024","journal-title":"Int. Microbiol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Shehreen, S., Chyou, T.Y., Fineran, P.C., and Brown, C.M. (2019). Genome-wide correlation analysis suggests different roles of CRISPR-Cas systems in the acquisition of antibiotic resistance genes in diverse species. Philos. Trans. R. Soc. Lond. B Biol. Sci., 374.","DOI":"10.1098\/rstb.2018.0384"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2744","DOI":"10.1038\/ismej.2016.47","article-title":"Genetic and life-history traits associated with the distribution of prophages in bacteria","volume":"10","author":"Touchon","year":"2016","journal-title":"ISME J."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Ho, P.L., Law, Y.H., Liu, M.C., Lau, A., Tong, M.K., Chow, K.H., Wu, A.K., Tse, C.W., Cheng, V.C., and Que, T.L. (2021). Improved Detection of mecA-Mediated beta-Lactam Resistance in Staphylococcus lugdunensis Using a New Oxacillin Salt Agar Screen. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.704552"},{"key":"ref_32","unstructured":"CLSI (2020). Performance Standards for Antimicrobial Susceptibility Testing, Clinical and Laboratory Standards Institute. [30th ed.]. CLSI Document M100."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1128\/AAC.00165-06","article-title":"Combination of multiplex PCRs for staphylococcal cassette chromosome mec type assignment: Rapid identification system for mec, ccr, and major differences in junkyard regions","volume":"51","author":"Kondo","year":"2007","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2640","DOI":"10.1093\/jac\/dks261","article-title":"Identification of acquired antimicrobial resistance genes","volume":"67","author":"Zankari","year":"2012","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"D566","DOI":"10.1093\/nar\/gkw1004","article-title":"CARD 2017: Expansion and model-centric curation of the comprehensive antibiotic resistance database","volume":"45","author":"Jia","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"D694","DOI":"10.1093\/nar\/gkv1239","article-title":"VFDB 2016: Hierarchical and refined dataset for big data analysis\u201410 years on","volume":"44","author":"Chen","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Clausen, P., Aarestrup, F.M., and Lund, O. (2018). Rapid and precise alignment of raw reads against redundant databases with KMA. BMC Bioinform., 19.","DOI":"10.1186\/s12859-018-2336-6"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"W347","DOI":"10.1093\/nar\/gkr485","article-title":"PHAST: A fast phage search tool","volume":"39","author":"Zhou","year":"2011","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/13\/6106\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:58:33Z","timestamp":1760032713000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/13\/6106"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,25]]},"references-count":38,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["ijms26136106"],"URL":"https:\/\/doi.org\/10.3390\/ijms26136106","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,25]]}}}