{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T22:05:07Z","timestamp":1790719507952,"version":"4.1.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2020,5,19]],"date-time":"2020-05-19T00:00:00Z","timestamp":1589846400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Tolerance (including persistence) and resistance result in increased survival under antibiotic pressure.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>We evaluated the interplay between resistance and tolerance to ciprofloxacin under therapeutic and killing conditions to determine the contribution of low-level quinolone resistance (LLQR) mechanisms to tolerance. We also determined how the interaction between resistance (LLQR phenotypes) and tolerance was modified under SOS response suppression.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Twelve isogenic Escherichia coli strains harbouring quinolone resistance mechanisms combined with SOS response deficiency and six clinical E. coli isolates (LLQR or non-LLQR) were evaluated. Survival (tolerance or persistence) assays were used to measure surviving bacteria after a short period (up to 4\u2009h) of bactericidal antibiotic treatment under therapeutic and killing concentrations of ciprofloxacin [1\u2009mg\/L, EUCAST\/CLSI breakpoint for resistance; and 2.5\u2009mg\/L, peak serum concentration (Cmax) of this drug].<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>QRDR substitutions (S83L in GyrA alone or combined with S80R in ParC) significantly increased the fraction of tolerant bacteria (2\u20134\u2009log10\u2009cfu\/mL) after exposure to ciprofloxacin at clinically relevant concentrations. The impact on tolerant bacteria due to SOS response suppression (including persistence mediated by the tisB gene) was reversed by LLQR mechanisms at therapeutic concentrations. Furthermore, no reduction in the fraction of tolerant bacteria due to SOS response suppression was observed when S83L in GyrA plus S80R in ParC were combined.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Tolerance and quinolone resistance mutations interact synergistically, giving LLQR mechanisms an additional role in allowing bacterial survival and evasion of therapeutic antimicrobial conditions by a combination of the two strategies. At clinically relevant concentrations, LLQR mechanisms reverse further impact of SOS response suppression in reducing bacterial tolerance.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkaa151","type":"journal-article","created":{"date-parts":[[2020,3,31]],"date-time":"2020-03-31T11:10:15Z","timestamp":1585653015000},"source":"Crossref","is-referenced-by-count":5,"title":["Role of low-level quinolone resistance in generating tolerance in Escherichia coli under therapeutic concentrations of ciprofloxacin"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4660-6553","authenticated-orcid":false,"given":"M","family":"Ortiz-Padilla","sequence":"first","affiliation":[{"name":"Unidad Cl\u00ednica de Enfermedades Infecciosas, Microbiolog\u00eda y Medicina Preventiva, Hospital Universitario Virgen Macarena, Seville, Spain"},{"name":"Departamento de Microbiolog\u00eda, Facultad de Medicina, Universidad de Sevilla, Sevilla, Spain"},{"name":"Red Espa\u00f1ola de Investigaci\u00f3n en Patolog\u00eda Infecciosa (REIPI), Instituto de Salud Carlos III, Madrid, Spain"},{"name":"Instituto de Biomedicina de Sevilla IBIS, Hospital Universitario Virgen Macarena\/CSIC\/Departamento de Microbiolog\u00eda, Universidad de Sevilla, Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Diaz-Diaz","sequence":"first","affiliation":[{"name":"Unidad Cl\u00ednica de Enfermedades Infecciosas, Microbiolog\u00eda y Medicina Preventiva, Hospital Universitario Virgen Macarena, Seville, Spain"},{"name":"Departamento de Microbiolog\u00eda, Facultad de Medicina, Universidad de Sevilla, Sevilla, Spain"},{"name":"Red Espa\u00f1ola de Investigaci\u00f3n en Patolog\u00eda Infecciosa (REIPI), Instituto de Salud Carlos III, Madrid, Spain"},{"name":"Instituto de Biomedicina de Sevilla IBIS, Hospital Universitario Virgen Macarena\/CSIC\/Departamento de Microbiolog\u00eda, Universidad de Sevilla, Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9855-6917","authenticated-orcid":false,"given":"J","family":"Machuca","sequence":"first","affiliation":[{"name":"Unidad Cl\u00ednica de Enfermedades Infecciosas, Microbiolog\u00eda y Medicina Preventiva, Hospital Universitario Virgen Macarena, Seville, Spain"},{"name":"Departamento de Microbiolog\u00eda, Facultad de Medicina, Universidad de Sevilla, Sevilla, Spain"},{"name":"Red Espa\u00f1ola de Investigaci\u00f3n en Patolog\u00eda Infecciosa (REIPI), Instituto de Salud Carlos III, Madrid, Spain"},{"name":"Instituto de Biomedicina de Sevilla IBIS, Hospital Universitario Virgen Macarena\/CSIC\/Departamento de Microbiolog\u00eda, Universidad de Sevilla, Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Tejada-Gonzalez","sequence":"first","affiliation":[{"name":"Departamento de Microbiolog\u00eda, Facultad de Medicina, Universidad de Sevilla, Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Recacha","sequence":"first","affiliation":[{"name":"Unidad Cl\u00ednica de Enfermedades Infecciosas, Microbiolog\u00eda y Medicina Preventiva, Hospital Universitario Virgen Macarena, Seville, Spain"},{"name":"Red Espa\u00f1ola de Investigaci\u00f3n en Patolog\u00eda Infecciosa (REIPI), Instituto de Salud Carlos III, Madrid, Spain"},{"name":"Instituto de Biomedicina de Sevilla IBIS, Hospital Universitario Virgen Macarena\/CSIC\/Departamento de Microbiolog\u00eda, Universidad de Sevilla, Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4038-6764","authenticated-orcid":false,"given":"F","family":"Docobo-P\u00e9rez","sequence":"first","affiliation":[{"name":"Departamento de Microbiolog\u00eda, Facultad de Medicina, Universidad de Sevilla, Sevilla, Spain"},{"name":"Red Espa\u00f1ola de Investigaci\u00f3n en Patolog\u00eda Infecciosa (REIPI), Instituto de Salud Carlos III, Madrid, Spain"},{"name":"Instituto de Biomedicina de Sevilla IBIS, Hospital Universitario Virgen Macarena\/CSIC\/Departamento de Microbiolog\u00eda, Universidad de Sevilla, Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8672-5891","authenticated-orcid":false,"given":"A","family":"Pascual","sequence":"first","affiliation":[{"name":"Unidad Cl\u00ednica de Enfermedades Infecciosas, Microbiolog\u00eda y Medicina Preventiva, Hospital Universitario Virgen Macarena, Seville, Spain"},{"name":"Departamento de Microbiolog\u00eda, Facultad de Medicina, Universidad de Sevilla, Sevilla, Spain"},{"name":"Red Espa\u00f1ola de Investigaci\u00f3n en Patolog\u00eda Infecciosa (REIPI), Instituto de Salud Carlos III, Madrid, Spain"},{"name":"Instituto de Biomedicina de Sevilla IBIS, Hospital Universitario Virgen Macarena\/CSIC\/Departamento de Microbiolog\u00eda, Universidad de Sevilla, Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2228-2294","authenticated-orcid":false,"given":"J M","family":"Rodr\u00edguez-Mart\u00ednez","sequence":"first","affiliation":[{"name":"Departamento de Microbiolog\u00eda, Facultad de Medicina, Universidad de Sevilla, Sevilla, Spain"},{"name":"Red Espa\u00f1ola de Investigaci\u00f3n en Patolog\u00eda Infecciosa (REIPI), Instituto de Salud Carlos III, Madrid, Spain"},{"name":"Instituto de Biomedicina de Sevilla IBIS, Hospital Universitario Virgen Macarena\/CSIC\/Departamento de Microbiolog\u00eda, Universidad de Sevilla, Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,5,19]]},"reference":[{"key":"2020051909580605900_dkaa151-B1","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.1126\/science.1099390","article-title":"Bacterial persistence as a phenotypic 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