{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T11:32:03Z","timestamp":1786361523140,"version":"build-2736575974"},"reference-count":23,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T00:00:00Z","timestamp":1786233600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea grant funded by the Korean government","award":["2022R1F1A1063113"],"award-info":[{"award-number":["2022R1F1A1063113"]}]},{"award":["2022R1F1A1063113"],"award-info":[{"award-number":["2022R1F1A1063113"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background:\u00a0Bacteroides fragilis is the most clinically important anaerobic bacterium and has shown increasing carbapenem resistance mediated by the cfiA metallo-\u03b2-lactamase. Although insertion sequence (IS)-mediated activation of cfiA is a well-recognized mechanism, the contribution of IS-independent genomic mechanisms remains incompletely characterized. This study investigated the phenotypic and genomic mechanisms of cfiA-associated carbapenem resistance in clinical B. fragilis isolates from Korea. Methods: Twenty-six non-duplicate carbapenem-nonsusceptible B. fragilis isolates were collected from three Korean institutions between 2022 and 2023. Antimicrobial susceptibility was tested by disk diffusion and agar dilution methods, and carbapenemase activity was assessed using the anaerobic carbapenem inactivation method (Ana-CIM) and the meropenem double-ended Etest. Whole-genome sequencing was performed to identify resistance determinants, insertion sequences, promoter structures, and multilocus sequence types. Results: Among 26 isolates, 12 (46.2%) were cfiA-positive and 14 (53.8%) were cfiA-negative. High-level resistance (imipenem MIC \u2265 32 mg\/L; meropenem MIC \u2265 128 mg\/L) was observed in four cfiA-positive isolates carrying activating IS elements (IS1187 or IS942) upstream of cfiA. Notably, three additional highly resistant cfiA-positive isolates lacked upstream IS elements and showed distinct genomic features, including tandem duplication of cfiA2 (SEV23_101), duplicated promoter architecture upstream of cfiA14 (SEV23_15), and high-level resistance associated with cfiA18 (SCL22_40). Ana-CIM yielded positive results only among isolates with meropenem MIC \u2265 128 mg\/L, whereas the meropenem double-ended Etest failed to discriminate cfiA-associated carbapenemase activity. Conclusions: These findings indicate that high-level carbapenem resistance in B. fragilis may be associated with several genomic features, including IS-mediated activation, increased cfiA gene dosage, and promoter amplification. Molecular characterization is therefore essential for accurate interpretation of carbapenem resistance in B. fragilis.<\/jats:p>","DOI":"10.3390\/antibiotics15080763","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T10:23:50Z","timestamp":1786357430000},"page":"763","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Diverse Genomic Mechanisms of cfiA Activation in Carbapenem-Resistant Bacteroides fragilis Clinical Isolates from Korea"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3821-3741","authenticated-orcid":false,"given":"Yangsoon","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Hanyang University College of Medicine, Seoul 04763, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8523-4126","authenticated-orcid":false,"given":"Hyukmin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoon Soo","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Department of Internal Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin 16995, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4933-5018","authenticated-orcid":false,"given":"Myungsook","family":"Kim","sequence":"additional","affiliation":[{"name":"Infectious Disease Research Center, Seoul Clinical Laboratories, Yongin 16954, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyungwon","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"},{"name":"Infectious Disease Research Center, Seoul Clinical Laboratories, Yongin 16954, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10096-023-04708-4","article-title":"Fifty years devoted to anaerobes: Historical, lessons, and highlights","volume":"43","author":"Dubreuil","year":"2024","journal-title":"Eur. 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