{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T05:52:39Z","timestamp":1788587559611,"version":"build-2803163510"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2020,11,4]],"date-time":"2020-11-04T00:00:00Z","timestamp":1604448000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministerio de Econom\u00eda y Competitividad\u2014co-financed by European Development Regional Fund \u2018A"},{"name":"Spanish Network for Research in Infectious Diseases (REIPI","award":["RD12\/0015"],"award-info":[{"award-number":["RD12\/0015"]}]},{"name":"Spanish Network for Research in Infectious Diseases (REIPI","award":["RD16\/0016"],"award-info":[{"award-number":["RD16\/0016"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,19]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n SOS response suppression (by RecA inactivation) has been postulated as a therapeutic strategy for potentiating antimicrobials against Enterobacterales.<\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n To evaluate the impact of RecA inactivation on the reversion and evolution of quinolone resistance using a collection of Escherichia coli clinical isolates.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Twenty-three E. coli clinical isolates, including isolates belonging to the high-risk clone ST131, were included. SOS response was suppressed by recA inactivation. Susceptibility to fluoroquinolones was determined by broth microdilution, growth curves and killing curves. Evolution of quinolone resistance was evaluated by mutant frequency and mutant prevention concentration (MPC).<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n RecA inactivation resulted in 2\u201316-fold reductions in fluoroquinolone MICs and modified EUCAST clinical category for several isolates, including ST131 clone isolates. Growth curves and time\u2013kill curves showed a clear disadvantage (up to 10 log10 cfu\/mL after 24\u2009h) for survival in strains with an inactivated SOS system. For recA-deficient mutants, MPC values decreased 4\u20138-fold, with values below the maximum serum concentration of ciprofloxacin. RecA inactivation led to a decrease in mutant frequency (\u2265103-fold) compared with isolates with unmodified SOS responses at ciprofloxacin concentrations of 4\u00d7MIC and 1\u2009mg\/L. These effects were also observed in ST131 clone isolates.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n While RecA inactivation does not reverse existing resistance, it is a promising strategy for increasing the effectiveness of fluoroquinolones against susceptible clinical isolates, including high-risk clone isolates.<\/jats:p>\n <\/jats:sec>","DOI":"10.1093\/jac\/dkaa448","type":"journal-article","created":{"date-parts":[[2020,10,7]],"date-time":"2020-10-07T19:13:56Z","timestamp":1602098036000},"page":"338-344","source":"Crossref","is-referenced-by-count":22,"title":["Effect of RecA inactivation on quinolone susceptibility and the evolution of resistance in clinical isolates of Escherichia coli<\/i>"],"prefix":"10.1093","volume":"76","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":"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":"E","family":"Recacha","sequence":"additional","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"}]},{"given":"B","family":"Gallego-Mesa","sequence":"additional","affiliation":[{"name":"Departamento de Microbiolog\u00eda, Facultad de Medicina, Universidad de Sevilla, Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Diaz-Diaz","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 Macarena\/CSIC\/Departamento de Microbiolog\u00eda, Universidad de Sevilla, Seville, Spain"},{"name":"Departamento de Microbiolog\u00eda, Facultad de Medicina, Universidad de Sevilla, Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Rojas-Granado","sequence":"additional","affiliation":[{"name":"Departamento de Microbiolog\u00eda, Facultad de Medicina, Universidad de Sevilla, Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Garc\u00eda-Duque","sequence":"additional","affiliation":[{"name":"Unidad Cl\u00ednica de Enfermedades Infecciosas, Microbiolog\u00eda y Medicina Preventiva, Hospital Universitario Virgen Macarena, 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":"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 Macarena\/CSIC\/Departamento de Microbiolog\u00eda, Universidad de Sevilla, Seville, Spain"},{"name":"Departamento de Microbiolog\u00eda, Facultad de Medicina, Universidad de Sevilla, Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Bl\u00e1zquez","sequence":"additional","affiliation":[{"name":"Red Espa\u00f1ola de Investigaci\u00f3n en Patolog\u00eda Infecciosa (REIPI), Instituto de Salud Carlos III, Madrid, Spain"},{"name":"Centro Nacional de Biotecnolog\u00eda, Consejo Superior de Investigaciones Cient\u00edficas, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Rodr\u00edguez-Rojas","sequence":"additional","affiliation":[{"name":"Institute of Biology, Freie Universit\u00e4t Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8672-5891","authenticated-orcid":false,"given":"A","family":"Pascual","sequence":"additional","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"},{"name":"Departamento de Microbiolog\u00eda, Facultad de Medicina, Universidad de Sevilla, Sevilla, 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":"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 Macarena\/CSIC\/Departamento de Microbiolog\u00eda, Universidad de Sevilla, Seville, Spain"},{"name":"Departamento de Microbiolog\u00eda, Facultad de Medicina, Universidad de Sevilla, Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,11,4]]},"reference":[{"key":"2021012006031650400_dkaa448-B1","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1126\/science.1176667","article-title":"Antibiotics for emerging pathogens","volume":"325","author":"Fischbach","year":"2009","journal-title":"Science"},{"key":"2021012006031650400_dkaa448-B2","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/nrg3351","article-title":"Understanding, predicting and manipulating the genotypic evolution of antibiotic resistance","volume":"14","author":"Palmer","year":"2013","journal-title":"Nat Rev Genet"},{"key":"2021012006031650400_dkaa448-B3","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1093\/femsre\/fuw005","article-title":"Escherichia coli: an old friend with new tidings","volume":"40","author":"Vila","year":"2016","journal-title":"FEMS Microbiol Rev"},{"key":"2021012006031650400_dkaa448-B4","doi-asserted-by":"crossref","first-page":"a816","DOI":"10.1136\/bmj.a816","article-title":"FDA adds \u2018black box\u2019 warning label to fluoroquinolone antibiotics","volume":"337","author":"Tanne","year":"2008","journal-title":"BMJ"},{"key":"2021012006031650400_dkaa448-B5","doi-asserted-by":"crossref","first-page":"355","DOI":"10.4140\/TCP.n.2020.355.","article-title":"Adverse events in older adults taking fluoroquinolones","volume":"35","author":"Leipold","year":"2020","journal-title":"Sr Care Pharm"},{"key":"2021012006031650400_dkaa448-B6","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1128\/CMR.00125-13","article-title":"Escherichia coli ST131, an intriguing clonal group","volume":"27","author":"Nicolas-Chanoine","year":"2014","journal-title":"Clin Microbiol Rev"},{"key":"2021012006031650400_dkaa448-B7","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1093\/jac\/dkt405","article-title":"Escherichia coli belonging to the worldwide emerging epidemic clonal group O25b\/ST131: risk factors and clinical implications","volume":"69","author":"L\u00f3pez-Cerero","year":"2014","journal-title":"J Antimicrob Chemother"},{"key":"2021012006031650400_dkaa448-B8","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.eimc.2012.09.005","article-title":"Escherichia coli O25b:H4\/ST131 are prevalent in Spain and are often not associated with ESBL or quinolone resistance","volume":"31","author":"L\u00f3pez-Cerero","year":"2013","journal-title":"Enferm Infecc Microbiol Clin"},{"key":"2021012006031650400_dkaa448-B9","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.mib.2012.07.007","article-title":"Antimicrobials as promoters of genetic variation","volume":"15","author":"Bl\u00e1zquez","year":"2012","journal-title":"Curr Opin Microbiol"},{"key":"2021012006031650400_dkaa448-B10","doi-asserted-by":"crossref","first-page":"3573","DOI":"10.1021\/acs.biochem.5b00109","article-title":"Targets for combating the evolution of acquired antibiotic resistance","volume":"54","author":"Culyba","year":"2015","journal-title":"Biochemistry"},{"key":"2021012006031650400_dkaa448-B11","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1111\/1574-6976.12077","article-title":"SOS, the formidable strategy of bacteria against aggressions","volume":"38","author":"Baharoglu","year":"2014","journal-title":"FEMS Microbiol Rev"},{"key":"2021012006031650400_dkaa448-B12","doi-asserted-by":"crossref","first-page":"e00163","DOI":"10.1128\/mSphere.00163-16","article-title":"Systematically altering bacterial SOS activity under stress reveals therapeutic strategies for potentiating antibiotics","volume":"1","author":"Mo","year":"2016","journal-title":"mSphere"},{"key":"2021012006031650400_dkaa448-B13","doi-asserted-by":"crossref","first-page":"e00971","DOI":"10.1128\/mBio.00971-17","article-title":"Quinolone resistance reversion by targeting the SOS response","volume":"8","author":"Recacha","year":"2017","journal-title":"mBio"},{"key":"2021012006031650400_dkaa448-B14","first-page":"66","article-title":"Suppression of the SOS response modifies spatiotemporal evolution, post-antibiotic effect, bacterial fitness and biofilm formation in quinolone-resistant Escherichia coli","volume":"74","author":"Recacha","year":"2019","journal-title":"J Antimicrob Chemother"},{"key":"2021012006031650400_dkaa448-B15","doi-asserted-by":"crossref","first-page":"aad3292","DOI":"10.1126\/science.aad3292","article-title":"Multidrug evolutionary strategies to reverse antibiotic resistance","volume":"351","author":"Baym","year":"2016","journal-title":"Science"},{"key":"2021012006031650400_dkaa448-B16","doi-asserted-by":"crossref","first-page":"14494","DOI":"10.1073\/pnas.1409800111","article-title":"Alternating antibiotic treatments constrain evolutionary paths to multidrug resistance","volume":"111","author":"Kim","year":"2014","journal-title":"Proc Natl Acad Sci USA"},{"key":"2021012006031650400_dkaa448-B17","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1093\/jac\/dkv392","article-title":"Assessment of a phenotypic algorithm to detect plasmid-mediated quinolone resistance in Enterobacteriaceae","volume":"71","author":"Rodr\u00edguez-Mart\u00ednez","year":"2016","journal-title":"J Antimicrob Chemother"},{"key":"2021012006031650400_dkaa448-B18","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.ijantimicag.2011.12.009","article-title":"Prevalence of plasmid-mediated quinolone resistance determinants qnr and aac(6\u2019)-Ib-cr in Escherichia coli and Klebsiella pneumoniae producing extended-spectrum \u03b2-lactamases in Spain","volume":"39","author":"Briales","year":"2012","journal-title":"Int J Antimicrob Agents"},{"key":"2021012006031650400_dkaa448-B19","doi-asserted-by":"crossref","first-page":"6640","DOI":"10.1073\/pnas.120163297","article-title":"One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products","volume":"97","author":"Datsenko","year":"2000","journal-title":"Proc Natl Acad Sci USA"},{"key":"2021012006031650400_dkaa448-B20","doi-asserted-by":"crossref","first-page":"3203","DOI":"10.1093\/jac\/dku308","article-title":"Interplay between plasmid-mediated and chromosomal-mediated fluoroquinolone resistance and bacterial fitness in Escherichia coli","volume":"69","author":"Machuca","year":"2014","journal-title":"J Antimicrob Chemother"},{"key":"2021012006031650400_dkaa448-B21"},{"key":"2021012006031650400_dkaa448-B22","year":"2020"},{"key":"2021012006031650400_dkaa448-B23","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1093\/jac\/dki136","article-title":"Mutant prevention concentrations of ciprofloxacin for urinary tract infection isolates of Escherichia coli","volume":"55","author":"Marcusson","year":"2005","journal-title":"J Antimicrob Chemother"},{"key":"2021012006031650400_dkaa448-B24","first-page":"426","volume-title":"Mandell, Douglas, and Bennett\u2019s Principles and Practice of Infectious Diseases","author":"Bennett","year":"2019","edition":"9th edn"},{"key":"2021012006031650400_dkaa448-B25","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1093\/jac\/dkq496","article-title":"Effect of recA inactivation on mutagenesis of Escherichia coli exposed to sublethal concentrations of antimicrobials","volume":"66","author":"Thi","year":"2011","journal-title":"J Antimicrob Chemother"},{"key":"2021012006031650400_dkaa448-B26","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.drup.2016.09.001","article-title":"Plasmid-mediated quinolone resistance: two decades on","volume":"29","author":"Rodr\u00edguez-Mart\u00ednez","year":"2016","journal-title":"Drug Resist Updat"},{"key":"2021012006031650400_dkaa448-B27","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1345\/aph.1C419","article-title":"Fluoroquinolone AUIC break points and the link to bacterial killing rates. Part 2: human trials","volume":"37","author":"Schentag","year":"2003","journal-title":"Ann Pharmacother"},{"key":"2021012006031650400_dkaa448-B28","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1038\/nature02241","article-title":"SOS response promotes horizontal dissemination of antibiotic resistance genes","volume":"427","author":"Beaber","year":"2004","journal-title":"Nature"},{"key":"2021012006031650400_dkaa448-B29","doi-asserted-by":"crossref","first-page":"e1001165","DOI":"10.1371\/journal.pgen.1001165","article-title":"Conjugative DNA transfer induces the bacterial SOS response and promotes antibiotic resistance development through integron activation","volume":"6","author":"Baharoglu","year":"2010","journal-title":"PLoS Genet"}],"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jac\/article-pdf\/76\/2\/338\/35925352\/dkaa448.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jac\/article-pdf\/76\/2\/338\/35925352\/dkaa448.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T14:09:48Z","timestamp":1611151788000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/76\/2\/338\/5956106"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,4]]},"references-count":29,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2020,11,4]]},"published-print":{"date-parts":[[2021,1,19]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dkaa448","relation":{},"ISSN":["0305-7453","1460-2091"],"issn-type":[{"value":"0305-7453","type":"print"},{"value":"1460-2091","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,2]]},"published":{"date-parts":[[2020,11,4]]}}}