{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T20:57:55Z","timestamp":1788641875751,"version":"build-2803163510"},"reference-count":90,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2023,7,26]],"date-time":"2023-07-26T00:00:00Z","timestamp":1690329600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Science and Technology, Ho Chi Minh City","award":["34\/2022\/ H\u0110-KHCNT-VU"],"award-info":[{"award-number":["34\/2022\/ H\u0110-KHCNT-VU"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>\n                      Fluoroquinolone (FQ) is a potent antibiotic class. However, resistance to this class emerges quickly which hinders its application. In this study, mechanisms leading to the emergence of multidrug-resistant (MDR)\n                      <jats:italic>Staphylococcus aureus<\/jats:italic>\n                      (\n                      <jats:italic>S<\/jats:italic>\n                      .\n                      <jats:italic>aureus<\/jats:italic>\n                      ) strains under FQ exposure were investigated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methodology<\/jats:title>\n                    <jats:p>\n                      <jats:italic>S<\/jats:italic>\n                      .\n                      <jats:italic>aureus<\/jats:italic>\n                      ATCC 29213 was serially exposed to ciprofloxacin (CIP), ofloxacin (OFL), or levofloxacin (LEV) at sub-minimum inhibitory concentrations (sub-MICs) for 12 days to obtain\n                      <jats:italic>S<\/jats:italic>\n                      .\n                      <jats:italic>aureus<\/jats:italic>\n                      -1 strains and antibiotic-free cultured for another 10 days to obtain\n                      <jats:italic>S<\/jats:italic>\n                      .\n                      <jats:italic>aureus<\/jats:italic>\n                      -2 strains. The whole genome (WGS) and target sequencing were applied to analyze genomic alterations; and RT-qPCR was used to access the expressions of efflux-related genes, alternative sigma factors, and genes involved in FQ resistance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A strong and irreversible increase of MICs was observed in all applied FQs (32 to 128 times) in all\n                      <jats:italic>S<\/jats:italic>\n                      .\n                      <jats:italic>aureus<\/jats:italic>\n                      -1 and remained 16 to 32 times in all\n                      <jats:italic>S<\/jats:italic>\n                      .\n                      <jats:italic>aureus<\/jats:italic>\n                      -2. WGS indicated 10 noticeable mutations occurring in all FQ-exposed\n                      <jats:italic>S<\/jats:italic>\n                      .\n                      <jats:italic>aureus<\/jats:italic>\n                      including 2 insdel mutations in SACOL0573 and\n                      <jats:italic>rimI<\/jats:italic>\n                      ; a synonymous mutation in\n                      <jats:italic>hslO<\/jats:italic>\n                      ; and 7 missense mutations located in an untranslated region. GrlA, was found mutated (R570H) in all\n                      <jats:italic>S<\/jats:italic>\n                      .\n                      <jats:italic>aureus<\/jats:italic>\n                      -1 and -2. Genes encoding for efflux pumps and their regulator (\n                      <jats:italic>norA<\/jats:italic>\n                      ,\n                      <jats:italic>norB<\/jats:italic>\n                      ,\n                      <jats:italic>norC<\/jats:italic>\n                      , and\n                      <jats:italic>mgrA<\/jats:italic>\n                      ); alternative sigma factors (\n                      <jats:italic>sigB<\/jats:italic>\n                      and\n                      <jats:italic>sigS<\/jats:italic>\n                      ); acetyltransferase (\n                      <jats:italic>rimI<\/jats:italic>\n                      ); methicillin resistance (\n                      <jats:italic>fmtB<\/jats:italic>\n                      ); and hypothetical protein BJI72_0645 were overexpressed in FQ-exposed strains.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The emergence of MDR\n                      <jats:italic>S<\/jats:italic>\n                      .\n                      <jats:italic>aureus<\/jats:italic>\n                      was associated with the mutations in the FQ-target sequences and the overexpression of efflux pump systems and their regulators.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0287973","type":"journal-article","created":{"date-parts":[[2023,7,26]],"date-time":"2023-07-26T14:33:23Z","timestamp":1690382003000},"page":"e0287973","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":28,"title":["Genomic alterations involved in fluoroquinolone resistance development in Staphylococcus aureus"],"prefix":"10.1371","volume":"18","author":[{"given":"Thuc Quyen","family":"Huynh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Van Nhi","family":"Tran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Van Chi","family":"Thai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4929-0187","authenticated-orcid":true,"given":"Hoang An","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ngoc Thuy Giang","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minh Khang","family":"Tran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thi Phuong Truc","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cat Anh","family":"Le","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le Thanh Ngan","family":"Ho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Navenaah Udaya","family":"Surian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swaine","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4869-1827","authenticated-orcid":true,"given":"Thi Thu Hoai","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,7,26]]},"reference":[{"key":"pone.0287973.ref001","doi-asserted-by":"crossref","first-page":"S350","DOI":"10.1086\/533591","article-title":"Pathogenesis of Methicillin-Resistant Staphylococcus aureus 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