{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T22:49:28Z","timestamp":1790376568149,"version":"4.1.0"},"reference-count":51,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2017,10,10]],"date-time":"2017-10-10T00:00:00Z","timestamp":1507593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2017,11,8]],"date-time":"2017-11-08T00:00:00Z","timestamp":1510099200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100004587","name":"MINECO | Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI14\/00940"],"award-info":[{"award-number":["PI14\/00940"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"MINECO | Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI13\/00063"],"award-info":[{"award-number":["PI13\/00063"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"MINECO | Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["REIPI RD12\/0015"],"award-info":[{"award-number":["REIPI RD12\/0015"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2017,11,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Suppression of the SOS response has been postulated as a therapeutic strategy for potentiating antimicrobial agents. We aimed to evaluate the impact of its suppression on reversing resistance using a model of isogenic strains of\n            <jats:italic>Escherichia coli<\/jats:italic>\n            representing multiple levels of quinolone resistance.\n            <jats:italic>E.\u00a0coli<\/jats:italic>\n            mutants exhibiting a spectrum of SOS activity were constructed from isogenic strains carrying quinolone resistance mechanisms with susceptible and resistant phenotypes. Changes in susceptibility were evaluated by static (MICs) and dynamic (killing curves or flow cytometry) methodologies. A peritoneal sepsis murine model was used to evaluate\n            <jats:italic>in vivo<\/jats:italic>\n            impact. Suppression of the SOS response was capable of resensitizing mutant strains with genes encoding three or four different resistance mechanisms (up to 15-fold reductions in MICs). Killing curve assays showed a clear disadvantage for survival (\u0394log\n            <jats:sub>10<\/jats:sub>\n            CFU per milliliter [CFU\/ml] of 8 log units after 24\u00a0h), and the\n            <jats:italic>in vivo<\/jats:italic>\n            efficacy of ciprofloxacin was significantly enhanced (\u0394log\n            <jats:sub>10<\/jats:sub>\n            CFU\/g of 1.76 log units) in resistant strains with a suppressed SOS response. This effect was evident even after short periods (60\u00a0min) of exposure. Suppression of the SOS response reverses antimicrobial resistance across a range of\n            <jats:italic>E.\u00a0coli<\/jats:italic>\n            phenotypes from reduced susceptibility to highly resistant, playing a significant role in increasing the\n            <jats:italic>in vivo<\/jats:italic>\n            efficacy.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            The rapid rise of antibiotic resistance in bacterial pathogens is now considered a major global health crisis. New strategies are needed to block the development of resistance and to extend the life of antibiotics. The SOS response is a promising target for developing therapeutics to reduce the acquisition of antibiotic resistance and enhance the bactericidal activity of antimicrobial agents such as quinolones. Significant questions remain regarding its impact as a strategy for the reversion or resensitization of antibiotic-resistant bacteria. To address this question, we have generated\n            <jats:italic>E.\u00a0coli<\/jats:italic>\n            mutants that exhibited a spectrum of SOS activity, ranging from a natural SOS response to a hypoinducible or constitutively suppressed response. We tested the effects of these mutations on quinolone resistance reversion under therapeutic concentrations in a set of isogenic strains carrying different combinations of chromosome- and plasmid-mediated quinolone resistance mechanisms with susceptible, low-level quinolone resistant, resistant, and highly resistant phenotypes. Our comprehensive analysis opens up a new strategy for reversing drug resistance by targeting the SOS response.\n          <\/jats:p>","DOI":"10.1128\/mbio.00971-17","type":"journal-article","created":{"date-parts":[[2017,10,11]],"date-time":"2017-10-11T00:10:30Z","timestamp":1507680630000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":73,"title":["Quinolone Resistance Reversion by Targeting the SOS Response"],"prefix":"10.1128","volume":"8","author":[{"given":"E.","family":"Recacha","sequence":"first","affiliation":[{"name":"Unidad de Enfermedades Infecciosas, Microbiolog\u00eda y Medicina Preventiva, Hospital Universitario Virgen Macarena, Seville, Spain"},{"name":"Departamento de Microbiolog\u00eda, Universidad de Sevilla, Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Machuca","sequence":"additional","affiliation":[{"name":"Unidad 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 del Roc\u00edo\/CSIC\/Universidad de Sevilla, Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"D\u00edaz de Alba","sequence":"additional","affiliation":[{"name":"Unidad de Enfermedades Infecciosas, Microbiolog\u00eda y Medicina Preventiva, Hospital Universitario Virgen Macarena, Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Ramos-G\u00fcelfo","sequence":"additional","affiliation":[{"name":"Unidad de Enfermedades Infecciosas, Microbiolog\u00eda y Medicina Preventiva, Hospital Universitario Virgen Macarena, Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Docobo-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Departamento de Microbiolog\u00eda, Universidad de Sevilla, 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 del Roc\u00edo\/CSIC\/Universidad de Sevilla, Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3014-1229","authenticated-orcid":false,"given":"J.","family":"Rodriguez-Beltr\u00e1n","sequence":"additional","affiliation":[{"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 del Roc\u00edo\/CSIC\/Universidad de Sevilla, Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0495-3848","authenticated-orcid":false,"given":"J.","family":"Bl\u00e1zquez","sequence":"additional","affiliation":[{"name":"Centro Nacional de Biotecnolog\u00eda, Consejo Superior de Investigaciones Cient\u00edficas, Madrid, Spain"},{"name":"Unidad de Enfermedades Infecciosas, Microbiolog\u00eda y Medicina Preventiva, Hospital Universitario Virgen del Rocio, Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Pascual","sequence":"additional","affiliation":[{"name":"Unidad de Enfermedades Infecciosas, Microbiolog\u00eda y Medicina Preventiva, Hospital Universitario Virgen Macarena, Seville, Spain"},{"name":"Departamento de Microbiolog\u00eda, Universidad de Sevilla, 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 del Roc\u00edo\/CSIC\/Universidad de Sevilla, Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2228-2294","authenticated-orcid":false,"given":"J. 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