{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T22:36:36Z","timestamp":1792190196352,"version":"4.4.0"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Acinetobacter baumannii<\/jats:italic>\n                      is a major nosocomial pathogen with extensive drug resistance (XDR) driven by \u03b2-lactamases, efflux systems, and biofilm formation. Plant-derived metabolites are promising multi-target modulators of these pathways.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Ten XDR\n                      <jats:italic>A. baumannii<\/jats:italic>\n                      isolates with strong biofilm and \u03b2-lactamase activity were screened; the most resistant (strain muks92) underwent whole-genome sequencing and\n                      <jats:italic>in-silico<\/jats:italic>\n                      analyses. Essential oil from\n                      <jats:italic>Thymus vulgaris<\/jats:italic>\n                      was profiled by GC\u2013MS, identifying o-cymene (32.95%) and gamma-terpinene (16.85%) as dominant constituents. Molecular docking (AutoDock Vina) targeted class D \u03b2-lactamase (6T1H), a biofilm-associated regulator (5HM6), and PBP1a\/efflux-associated protein (8YR0), with post-docking visualization and AMBER-relaxed stability checks. Antibiofilm activity was quantified by crystal-violet microtiter assay, and ESBL activity by nitrocefin hydrolysis. Multilocus sequence typing (MLST), resistance\/virulence gene mining, and mobile genetic element mapping were performed on the genome. Pharmacokinetic\/toxicity properties for key metabolites were predicted using ADMET-AI.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      GC\u2013MS established a cymene\/terpinene-rich chemotype. Docking showed favorable hydrophobic\/\n                      <jats:italic>\u03c0<\/jats:italic>\n                      \u2013alkyl encapsulation of o-cymene and gamma-terpinene within catalytic or transport pockets of 6T1H, 5HM6, and 8YR0, consistent with steric gating of substrate access.\n                      <jats:italic>T. vulgaris<\/jats:italic>\n                      significantly reduced biofilm biomass versus control (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.0002), and lowered ESBL activity (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.0017). The muks92 genome (3.98\u202fMb; ST1104) carried a complex resistome including blaOXA-90, blaOXA-72, blaADC-25, blaCARB-14, armA, aac(6\u2032)-Ian, aadA5, sul1\/sul2, mph(E)\/msr(E), alongside virulence loci (bap, bfmRS, ompA, pgaABCD, csuA\/B\u2013E) and siderophore systems (bas\/bau\/bar), with multiple insertion sequences and an IncA\/C2 replicon. ADMET predictions supported good oral absorption and low acute toxicity; gamma-terpinene showed broader tissue distribution (predicted VDss \u2248 7.24\u202fL\/kg) and a longer half-life (~4.6\u202fh) than o-cymene.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>T. vulgaris<\/jats:italic>\n                      metabolites, particularly gamma-terpinene, exhibit multi-target inhibitory potential against resistance and virulence pathways in XDR\n                      <jats:italic>A. baumannii<\/jats:italic>\n                      (muks92), aligning\n                      <jats:italic>in-silico<\/jats:italic>\n                      interactions with measurable antibiofilm and ESBL attenuation\n                      <jats:italic>in vitro<\/jats:italic>\n                      . Given the predictive nature of docking\/ADMET outputs, targeted enzyme kinetics, standardized MIC\/MBC testing, cytotoxicity assays, and in-vivo validation are warranted before therapeutic translation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2025.1680686","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T06:36:40Z","timestamp":1765953400000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Integrated in silico\u2013in vitro and pharmacokinetic profiling of Thymus vulgaris-derived metabolites targeting multidrug resistance pathways in extensively drug-resistant Acinetobacter baumannii (muks92)"],"prefix":"10.3389","volume":"16","author":[{"given":"Ali Hazim","family":"Abdulkareem","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Mukhles Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Safaa","family":"Abed Latef Al-Meani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elham Hazeim","family":"Abdulkareem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,17]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"e14998","DOI":"10.1111\/ijcp.14998","article-title":"Molecular epidemiology of carbapenem-resistant Acinetobacter baumannii isolated from three major hospitals in Jordan","volume":"75","author":"Ababneh","year":"2021","journal-title":"Int. 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