{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T22:48:39Z","timestamp":1792622919329,"version":"4.5.0"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T00:00:00Z","timestamp":1765324800000},"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. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      To explore the molecular basis of ciprofloxacin resistance in\n                      <jats:italic>N. farcinica<\/jats:italic>\n                      , providing a scientific basis for clinical antibiotic use and controlling the spread of resistant strains.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We analyzed 20\n                      <jats:italic>N. farcinica<\/jats:italic>\n                      strains. The quinolone resistance-determining regions (QRDRs) of\n                      <jats:italic>gyrA<\/jats:italic>\n                      and\n                      <jats:italic>gyrB<\/jats:italic>\n                      were sequenced and compared to the reference strain IFM 10152. The impact of efflux pumps was assessed by measuring changes in ciprofloxacin minimum inhibitory concentration (MIC) in the presence of three efflux pump inhibitors (EPIs). RT-qPCR was used to quantify the expression of 2 porin genes and 26 putative major facilitator superfamily (MFS) efflux pump genes, with and without ciprofloxacin induction.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Sequencing revealed no resistance-associated mutations in\n                      <jats:italic>gyrA<\/jats:italic>\n                      or\n                      <jats:italic>gyrB<\/jats:italic>\n                      . The ciprofloxacin MICs were significantly reduced (4- to 64-fold) upon exposure to EPIs, confirming efflux pump activity. Porin gene expression was modestly downregulation but did not correlate with resistance. Notably, three MFS efflux pump genes (\n                      <jats:italic>nfa56470<\/jats:italic>\n                      ,\n                      <jats:italic>nfa29840<\/jats:italic>\n                      , and\n                      <jats:italic>nfa34160<\/jats:italic>\n                      ) were significantly upregulated under ciprofloxacin pressure. Among these,\n                      <jats:italic>nfa56470<\/jats:italic>\n                      emerged as the most consistently and highly overexpressed gene in resistant strains.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study identifies the overexpression of specific MFS efflux pump genes, particularly\n                      <jats:italic>nfa56470<\/jats:italic>\n                      , as a primary mechanism of ciprofloxacin resistance in\n                      <jats:italic>N. farcinica<\/jats:italic>\n                      , supported by both gene expression data and functional EPI assays. This finding provides a clear target for future research into combating nocardial resistance.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2025.1708290","type":"journal-article","created":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T07:14:34Z","timestamp":1765350874000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Overexpression of the major facilitator superfamily efflux pump gene nfa56470 mediates ciprofloxacin resistance in Nocardia farcinica"],"prefix":"10.3389","volume":"15","author":[{"given":"Chenchen","family":"Si","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Poshi","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shixuan","family":"Hua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenjun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"656","DOI":"10.3390\/pathogens14070656","article-title":"Clinical features of pulmonary nocardiosis and diagnostic value of metagenomic next-generation sequencing: A retrospective study","volume":"14","author":"Chen","year":"2025","journal-title":"Pathogens."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.03596-23","article-title":"Identification of environmental Actinobacteria in buildings by means of chemotaxonomy, 16S rRNA sequencing, and MALDITOF MS","volume":"12","author":"Chudzik","year":"2024","journal-title":"Microbiol. 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