{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T02:51:59Z","timestamp":1788403919247,"version":"build-2803163510"},"reference-count":159,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,8,24]],"date-time":"2025-08-24T00:00:00Z","timestamp":1755993600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union-Next Generation EU","award":["BG-RRP-2.004-0005"],"award-info":[{"award-number":["BG-RRP-2.004-0005"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Linezolid (LNZ) is a synthetic oxazolidinone antibiotic that inhibits bacterial protein synthesis through binding to ribosomal RNA, also preventing the assembly of the initiation complex during translation. It is one of the last-line therapeutic options for serious infections caused by problematic Gram-positive pathogens, including vancomycin-resistant and multidrug-resistant Enterococcus species. Data from recent large-scale studies show a 2.5-fold increase in the prevalence of clinical LNZ-resistant enterococci (LRE) over the past decade with a global detection rate of 1.1% for LNZ-resistant E. faecium (LREfm) and 2.2% for LNZ-resistant E. faecalis (LREfs). Most reported cases have originated from China, followed by South Korea and the United States. LREfm typically belongs to the high-risk clonal complex 17, whereas LREfs demonstrates a heterogeneous population structure. Mutations in the 23S rRNA and ribosomal proteins, as well as acquired resistance genes such as cfr, optrA, and poxtA are involved in the development of LNZ resistance among enterococci. Whole-genome sequencing (WGS) has been recognized as a gold standard for identifying the underlying molecular mechanisms. It exposes that numerous LRE isolates possess multiple LNZ resistance determinants and mutations, further complicating the treatment strategies. The present review article summarizes all known mutational and non-mutational LNZ resistance mechanisms and presents a global overview of WGS-based studies with emphasis on resistome analysis of clinical LREfs and LREfm isolates published in the literature during the period 2014\u20132025.<\/jats:p>","DOI":"10.3390\/ijms26178207","type":"journal-article","created":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:10:36Z","timestamp":1756080636000},"page":"8207","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Linezolid in the Focus of Antimicrobial Resistance of Enterococcus Species: A Global Overview of Genomic Studies"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9431-9511","authenticated-orcid":false,"given":"Slavil","family":"Peykov","sequence":"first","affiliation":[{"name":"Department of Genetics, Faculty of Biology, University of Sofia \u201cSt. Kliment Ohridski\u201d, 8 Dragan Tzankov Blvd., 1164 Sofia, Bulgaria"},{"name":"BioInfoTech Laboratory, Sofia Tech Park, 111 Tsarigradsko Shose Blvd., 1784 Sofia, Bulgaria"},{"name":"Department of Medical Microbiology \u201cCorr. Mem. Prof. Ivan Mitov, MD, DMSc\u201d, Faculty of Medicine, Medical University of Sofia, 2 Zdrave Str., 1431 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6477-1749","authenticated-orcid":false,"given":"Boris","family":"Kirov","sequence":"additional","affiliation":[{"name":"BioInfoTech Laboratory, Sofia Tech Park, 111 Tsarigradsko Shose Blvd., 1784 Sofia, Bulgaria"},{"name":"Department Industrial Automation, Technical University of Sofia, 1756 Sofia, Bulgaria"},{"name":"Faculty of German Engineering Education and Industrial Management (FDIBA), Technical University of Sofia, 1756 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5197-1849","authenticated-orcid":false,"given":"Tanya","family":"Strateva","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology \u201cCorr. Mem. Prof. Ivan Mitov, MD, DMSc\u201d, Faculty of Medicine, Medical University of Sofia, 2 Zdrave Str., 1431 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.2147\/DDDT.S164515","article-title":"Linezolid: A Review of Its Properties, Function, and Use in Critical Care","volume":"12","author":"Hashemian","year":"2018","journal-title":"Drug Des. Dev. 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