{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T01:11:16Z","timestamp":1791421876180,"version":"4.3.3"},"update-to":[{"DOI":"10.1371\/journal.pgen.1011840","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T00:00:00Z","timestamp":1757030400000}}],"reference-count":77,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R21AI182745"],"award-info":[{"award-number":["R21AI182745"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R21AI185486"],"award-info":[{"award-number":["R21AI185486"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Princeton University School of Engineering and Applied Science"},{"name":"Omenn Darling Bioengineering Institute"}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>Studies have shown that DNA damage repair systems, including homologous recombination (HR) and the SOS response, are important for fluoroquinolone (FQ) persistence of <jats:italic><jats:italic>Escherichia coli<\/jats:italic><\/jats:italic>, which has been the workhorse organism of persister research. We sought to explore whether those systems are also important for FQ persistence of <jats:italic><jats:italic>Pseudomonas aeruginosa<\/jats:italic><\/jats:italic>, a common cause of lung infections in cystic fibrosis patients, which can be treated with FQs such as ciprofloxacin (CIP). Notably, <jats:italic><jats:italic>P. aeruginosa<\/jats:italic><\/jats:italic> has important differences in its DNA damage repair capabilities compared to <jats:italic><jats:italic>E. coli<\/jats:italic><\/jats:italic> that include the machinery needed to conduct non-homologous end-joining (NHEJ), Ku and LigD. Using a genetic approach, we found that loss of HR significantly depressed persister levels of <jats:italic><jats:italic>P. aeruginosa<\/jats:italic><\/jats:italic> to CIP during stationary-phase, but not in exponential-phase. This differed from <jats:italic><jats:italic>E. coli<\/jats:italic><\/jats:italic> grown in identical conditions, where loss of HR reduced survival in both stationary- and exponential-phase populations. Similarly, an inability to induce the SOS response reduced survival during both growth phases for <jats:italic><jats:italic>E. coli<\/jats:italic><\/jats:italic> but only in stationary-phase for <jats:italic><jats:italic>P. aeruginosa<\/jats:italic><\/jats:italic>. Loss of NHEJ machinery in <jats:italic><jats:italic>P. aeruginosa<\/jats:italic><\/jats:italic> did not impact persister levels during stationary- or exponential-phase, whereas overexpression of NHEJ machinery in <jats:italic><jats:italic>P. aeruginosa<\/jats:italic><\/jats:italic> had toxic effects. In addition, the generality of findings to another FQ, levofloxacin, and a recent clinical isolate, MRSN 1612, were confirmed. These results demonstrate that HR and the SOS response are important to CIP persistence of stationary-phase <jats:italic><jats:italic>P. aeruginosa<\/jats:italic><\/jats:italic>, dispensable to CIP persisters in growing <jats:italic><jats:italic>P. aeruginosa<\/jats:italic><\/jats:italic> cultures, and that the contributions of systems to <jats:italic><jats:italic>E. coli<\/jats:italic><\/jats:italic> persistence do not directly translate to persisters of <jats:italic><jats:italic>P. aeruginosa<\/jats:italic><\/jats:italic>.<\/jats:p>","DOI":"10.1371\/journal.pgen.1011840","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T17:46:22Z","timestamp":1756835182000},"page":"e1011840","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Conservation and divergence of ciprofloxacin persister survival mechanisms between Pseudomonas aeruginosa and Escherichia coli"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0912-5795","authenticated-orcid":true,"given":"Gabrielle","family":"Leon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5707-8894","authenticated-orcid":true,"given":"Mark P.","family":"Brynildsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,9,2]]},"reference":[{"issue":"5","key":"pgen.1011840.ref001","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1038\/nrmicro.2016.34","article-title":"Distinguishing between resistance, tolerance and persistence to antibiotic treatment","volume":"14","author":"A Brauner","year":"2016","journal-title":"Nat Rev Microbiol"},{"issue":"7","key":"pgen.1011840.ref002","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1038\/s41579-019-0196-3","article-title":"Definitions and guidelines for research on antibiotic persistence","volume":"17","author":"NQ Balaban","year":"2019","journal-title":"Nat Rev Microbiol"},{"issue":"12","key":"pgen.1011840.ref003","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1009112","article-title":"Bacterial persisters in long-term infection: Emergence and fitness in a complex host environment","volume":"16","author":"JA Bartell","year":"2020","journal-title":"PLoS Pathog"},{"issue":"6320","key":"pgen.1011840.ref004","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0140-6736(00)74210-3","article-title":"Treatment of staphylococcal infections with penicillin by intermittent sterilisation","volume":"244","author":"JW Bigger","year":"1944","journal-title":"The Lancet"},{"issue":"1","key":"pgen.1011840.ref005","doi-asserted-by":"crossref","first-page":"2200","DOI":"10.1038\/s41467-020-15966-7","article-title":"Intracellular Staphylococcus aureus persisters upon antibiotic exposure","volume":"11","author":"F Peyrusson","year":"2020","journal-title":"Nat Commun"},{"issue":"6167","key":"pgen.1011840.ref006","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1126\/science.1244705","article-title":"Internalization of Salmonella by macrophages induces formation of nonreplicating persisters","volume":"343","author":"S Helaine","year":"2014","journal-title":"Science"},{"issue":"6115","key":"pgen.1011840.ref007","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1126\/science.1229858","article-title":"Dynamic persistence of antibiotic-stressed mycobacteria","volume":"339","author":"Y Wakamoto","year":"2013","journal-title":"Science"},{"issue":"3","key":"pgen.1011840.ref008","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2314514121","article-title":"In-patient evolution of a high-persister Escherichia coli strain with reduced in vivo antibiotic susceptibility","volume":"121","author":"JB Parsons","year":"2024","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"6","key":"pgen.1011840.ref009","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.tig.2019.03.007","article-title":"General Mechanisms Leading to Persister Formation and Awakening","volume":"35","author":"D Wilmaerts","year":"2019","journal-title":"Trends Genet"},{"issue":"1","key":"pgen.1011840.ref010","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1186\/s12890-016-0339-5","article-title":"Cystic fibrosis lung environment and Pseudomonas aeruginosa infection","volume":"16","author":"AY Bhagirath","year":"2016","journal-title":"BMC Pulm Med"},{"issue":"1","key":"pgen.1011840.ref011","doi-asserted-by":"crossref","first-page":"199","DOI":"10.3390\/cells12010199","article-title":"Pseudomonas aeruginosa: Infections, Animal Modeling, and Therapeutics","volume":"12","author":"SJ Wood","year":"2023","journal-title":"Cells"},{"issue":"18","key":"pgen.1011840.ref012","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1007\/s40265-021-01635-6","article-title":"The Epidemiology and Pathogenesis and Treatment of Pseudomonas aeruginosa Infections: An Update","volume":"81","author":"D Reynolds","year":"2021","journal-title":"Drugs"},{"issue":"23","key":"pgen.1011840.ref013","doi-asserted-by":"crossref","first-page":"6191","DOI":"10.1128\/JB.01651-09","article-title":"Emergence of Pseudomonas aeruginosa strains producing high levels of persister cells in patients with cystic fibrosis","volume":"192","author":"LR Mulcahy","year":"2010","journal-title":"J Bacteriol"},{"issue":"3","key":"pgen.1011840.ref014","doi-asserted-by":"crossref","first-page":"426","DOI":"10.3390\/pathogens12030426","article-title":"Genome Analysis of Pseudomonas aeruginosa Strains from Chronically Infected Patients with High Levels of Persister Formation","volume":"12","author":"AA Baiomy","year":"2023","journal-title":"Pathogens"},{"issue":"1","key":"pgen.1011840.ref015","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1038\/s41467-019-09058-4","article-title":"Enhanced antibiotic resistance development from fluoroquinolone persisters after a single exposure to antibiotic","volume":"10","author":"TC Barrett","year":"2019","journal-title":"Nat Commun"},{"issue":"6327","key":"pgen.1011840.ref016","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1126\/science.aaj2191","article-title":"Antibiotic tolerance facilitates the evolution of resistance","volume":"355","author":"I Levin-Reisman","year":"2017","journal-title":"Science"},{"issue":"5","key":"pgen.1011840.ref017","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1038\/s41396-019-0344-9","article-title":"Bacterial persistence promotes the evolution of antibiotic resistance by increasing survival and mutation rates","volume":"13","author":"EM Windels","year":"2019","journal-title":"ISME J"},{"key":"pgen.1011840.ref018","doi-asserted-by":"crossref","first-page":"212527","DOI":"10.7573\/dic.212527","article-title":"How to manage Pseudomonas aeruginosa infections","volume":"7","author":"M Bassetti","year":"2018","journal-title":"Drugs Context"},{"issue":"10","key":"pgen.1011840.ref019","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.3390\/antibiotics11101432","article-title":"Antimicrobial Treatment of Pseudomonas aeruginosa Severe Sepsis","volume":"11","author":"J Zakhour","year":"2022","journal-title":"Antibiotics (Basel)"},{"issue":"3","key":"pgen.1011840.ref020","first-page":"377","article-title":"DNA gyrase, topoisomerase IV, and the 4-quinolones","volume":"61","author":"K Drlica","year":"1997","journal-title":"Microbiol Mol Biol Rev"},{"issue":"2","key":"pgen.1011840.ref021","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1128\/AAC.01617-06","article-title":"Quinolone-mediated bacterial death","volume":"52","author":"K Drlica","year":"2008","journal-title":"Antimicrob Agents Chemother"},{"issue":"23","key":"pgen.1011840.ref022","doi-asserted-by":"crossref","first-page":"5662","DOI":"10.3390\/molecules25235662","article-title":"Quinolones: Mechanism, Lethality and Their Contributions to Antibiotic Resistance","volume":"25","author":"NG Bush","year":"2020","journal-title":"Molecules"},{"issue":"9","key":"pgen.1011840.ref023","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.1128\/AAC.35.9.1824","article-title":"Bactericidal effects of antibiotics on slowly growing and nongrowing bacteria","volume":"35","author":"RH Eng","year":"1991","journal-title":"Antimicrob Agents Chemother"},{"issue":"1","key":"pgen.1011840.ref024","doi-asserted-by":"crossref","DOI":"10.1128\/ecosalplus.5.4.3","article-title":"The SOS Regulatory Network","volume":"3","author":"LA Simmons","year":"2008","journal-title":"EcoSal Plus"},{"issue":"4","key":"pgen.1011840.ref025","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1002\/em.22267","article-title":"The SOS system: A complex and tightly regulated response to DNA damage","volume":"60","author":"KH Maslowska","year":"2019","journal-title":"Environ Mol Mutagen"},{"issue":"1","key":"pgen.1011840.ref026","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1093\/genetics\/158.1.41","article-title":"Comparative gene expression profiles following UV exposure in wild-type and SOS-deficient Escherichia coli","volume":"158","author":"J Courcelle","year":"2001","journal-title":"Genetics"},{"issue":"20","key":"pgen.1011840.ref027","doi-asserted-by":"crossref","first-page":"7101","DOI":"10.1128\/JB.00807-06","article-title":"Defining the Pseudomonas aeruginosa SOS response and its role in the global response to the antibiotic ciprofloxacin","volume":"188","author":"RT Cirz","year":"2006","journal-title":"J Bacteriol"},{"issue":"1","key":"pgen.1011840.ref028","article-title":"The EcoCyc Database (2023)","volume":"11","author":"PD Karp","year":"2023","journal-title":"EcoSal Plus"},{"issue":"11","key":"pgen.1011840.ref029","doi-asserted-by":"crossref","first-page":"981","DOI":"10.2174\/156802609789630947","article-title":"Quinolones: action and resistance updated","volume":"9","author":"K Drlica","year":"2009","journal-title":"Curr Top Med Chem"},{"issue":"3","key":"pgen.1011840.ref030","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1111\/j.1365-2958.2006.05275.x","article-title":"Lethal fragmentation of bacterial chromosomes mediated by DNA gyrase and quinolones","volume":"61","author":"M Malik","year":"2006","journal-title":"Mol Microbiol"},{"key":"pgen.1011840.ref031","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/1471-2180-9-69","article-title":"Rapid assessment of the effect of ciprofloxacin on chromosomal DNA from Escherichia coli using an in situ DNA fragmentation assay","volume":"9","author":"M Tamayo","year":"2009","journal-title":"BMC Microbiol"},{"issue":"4","key":"pgen.1011840.ref032","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1128\/jb.169.4.1499-1508.1987","article-title":"Characterization of the Pseudomonas aeruginosa recA analog and its protein product: rec-102 is a mutant allele of the P. aeruginosa PAO recA gene","volume":"169","author":"TA Kokjohn","year":"1987","journal-title":"J Bacteriol"},{"issue":"3","key":"pgen.1011840.ref033","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1128\/mr.58.3.401-465.1994","article-title":"Biochemistry of homologous recombination in Escherichia coli","volume":"58","author":"SC Kowalczykowski","year":"1994","journal-title":"Microbiol Rev"},{"issue":"4","key":"pgen.1011840.ref034","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1128\/MMBR.00020-08","article-title":"RecBCD enzyme and the repair of double-stranded DNA breaks","volume":"72","author":"MS Dillingham","year":"2008","journal-title":"Microbiol Mol Biol Rev"},{"issue":"11","key":"pgen.1011840.ref035","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1038\/nrmicro1768","article-title":"Bacterial DNA repair by non-homologous end joining","volume":"5","author":"S Shuman","year":"2007","journal-title":"Nat Rev Microbiol"},{"issue":"1","key":"pgen.1011840.ref036","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1074\/jbc.M410110200","article-title":"A primer-dependent polymerase function of pseudomonas aeruginosa ATP-dependent DNA ligase (LigD)","volume":"280","author":"H Zhu","year":"2005","journal-title":"J Biol Chem"},{"issue":"2","key":"pgen.1011840.ref037","article-title":"Comparative and evolutionary analysis of the bacterial homologous recombination systems","volume":"1","author":"EPC Rocha","year":"2005","journal-title":"PLoS Genet"},{"issue":"12","key":"pgen.1011840.ref038","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1000760","article-title":"SOS response induces persistence to fluoroquinolones in Escherichia coli","volume":"5","author":"T D\u00f6rr","year":"2009","journal-title":"PLoS Genet"},{"issue":"4","key":"pgen.1011840.ref039","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1534\/genetics.113.152306","article-title":"Tolerance of Escherichia coli to fluoroquinolone antibiotics depends on specific components of the SOS response pathway","volume":"195","author":"A Theodore","year":"2013","journal-title":"Genetics"},{"issue":"5","key":"pgen.1011840.ref040","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.00731-15","article-title":"Stationary-Phase Persisters to Ofloxacin Sustain DNA Damage and Require Repair Systems Only during Recovery","volume":"6","author":"KG V\u00f6lzing","year":"2015","journal-title":"mBio"},{"issue":"27","key":"pgen.1011840.ref041","article-title":"Timing of DNA damage responses impacts persistence to fluoroquinolones","volume":"115","author":"WWK Mok","year":"2018","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"10","key":"pgen.1011840.ref042","doi-asserted-by":"crossref","DOI":"10.1016\/j.cub.2021.02.040","article-title":"Ploidy is an important determinant of fluoroquinolone persister survival","volume":"31","author":"AM Murawski","year":"2021","journal-title":"Curr Biol"},{"issue":"5","key":"pgen.1011840.ref043","doi-asserted-by":"crossref","DOI":"10.1128\/mbio.00374-24","article-title":"Differential impacts of DNA repair machinery on fluoroquinolone persisters with different chromosome abundances","volume":"15","author":"J Tang","year":"2024","journal-title":"mBio"},{"key":"pgen.1011840.ref044","doi-asserted-by":"crossref","DOI":"10.3390\/microorganisms10020286","article-title":"Fluoroquinolone persistence in Escherichia coli requires DNA repair despite differing between starving populations","volume":"10","author":"AS Lemma","year":"2022","journal-title":"Microorganisms"},{"issue":"6","key":"pgen.1011840.ref045","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.aav9462","article-title":"Single-cell imaging and characterization of Escherichia coli persister cells to ofloxacin in exponential cultures","volume":"5","author":"F Goormaghtigh","year":"2019","journal-title":"Sci Adv"},{"issue":"1","key":"pgen.1011840.ref046","article-title":"Metabolic and transcriptional activities underlie stationary-phase Pseudomonas aeruginosa sensitivity to Levofloxacin","volume":"12","author":"PJ Hare","year":"2024","journal-title":"Microbiol Spectr"},{"issue":"6","key":"pgen.1011840.ref047","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1046\/j.1365-2958.2000.01826.x","article-title":"Identification of additional genes belonging to the LexA regulon in Escherichia coli","volume":"35","author":"AR Fern\u00e1ndez De Henestrosa","year":"2000","journal-title":"Mol Microbiol"},{"issue":"3","key":"pgen.1011840.ref048","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/S0014-5793(01)02589-3","article-title":"Identification of bacterial homologues of the Ku DNA repair proteins","volume":"500","author":"AJ Doherty","year":"2001","journal-title":"FEBS Lett"},{"issue":"4","key":"pgen.1011840.ref049","doi-asserted-by":"crossref","DOI":"10.1093\/jacamr\/dlab179","article-title":"A panel of diverse Pseudomonas aeruginosa clinical isolates for research and development","volume":"3","author":"F Lebreton","year":"2021","journal-title":"JAC Antimicrob Resist"},{"issue":"5","key":"pgen.1011840.ref050","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1111\/j.1574-6976.2010.00218.x","article-title":"Carbon catabolite repression in Pseudomonas\u00a0: optimizing metabolic versatility and interactions with the environment","volume":"34","author":"F Rojo","year":"2010","journal-title":"FEMS Microbiol Rev"},{"issue":"3","key":"pgen.1011840.ref051","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1093\/nar\/gkac1223","article-title":"Genome-wide mapping of fluoroquinolone-stabilized DNA gyrase cleavage sites displays drug specific effects that correlate with bacterial persistence","volume":"51","author":"J Tang","year":"2023","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"pgen.1011840.ref052","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0170719","article-title":"DNA Polymerases ImuC and DinB Are Involved in DNA Alkylation Damage Tolerance in Pseudomonas aeruginosa and Pseudomonas putida","volume":"12","author":"T Jatsenko","year":"2017","journal-title":"PLoS One"},{"issue":"12","key":"pgen.1011840.ref053","doi-asserted-by":"crossref","first-page":"6147","DOI":"10.1073\/pnas.76.12.6147","article-title":"Identification of the lexA gene product of Escherichia coli K-12","volume":"76","author":"JW Little","year":"1979","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"pgen.1011840.ref054","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1073\/pnas.74.1.300","article-title":"A mutant of Escherichia coli showing constitutive expression of the lysogenic induction and error-prone DNA repair pathways","volume":"74","author":"DW Mount","year":"1977","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"11","key":"pgen.1011840.ref055","doi-asserted-by":"crossref","first-page":"1820","DOI":"10.1038\/nprot.2015.115","article-title":"Precision-engineering the Pseudomonas aeruginosa genome with two-step allelic exchange","volume":"10","author":"LR Hmelo","year":"2015","journal-title":"Nat Protoc"},{"key":"pgen.1011840.ref056","volume-title":"World Health Organization Model List of Essential Medicines - 23rd List (2023)","author":"WHO","year":"2023"},{"key":"pgen.1011840.ref057","volume-title":"Critically important antimicrobials for human medicine, 6th revision","author":"WHO","year":"2019"},{"issue":"8","key":"pgen.1011840.ref058","article-title":"The AcrAB-TolC Efflux Pump Impacts Persistence and Resistance Development in Stationary-Phase Escherichia coli following Delafloxacin Treatment","volume":"65","author":"BA Byrd","year":"2021","journal-title":"Antimicrob Agents Chemother"},{"issue":"9","key":"pgen.1011840.ref059","doi-asserted-by":"crossref","first-page":"110427","DOI":"10.1016\/j.celrep.2022.110427","article-title":"Transcription-coupled DNA repair underlies variation in persister awakening and the emergence of resistance","volume":"38","author":"D Wilmaerts","year":"2022","journal-title":"Cell Rep"},{"issue":"32","key":"pgen.1011840.ref060","doi-asserted-by":"crossref","first-page":"24481","DOI":"10.1016\/S0021-9258(20)80551-1","article-title":"Escherichia coli topoisomerase IV. Purification, characterization, subunit structure, and subunit interactions.","volume":"268","author":"H Peng","year":"1993","journal-title":"Journal of Biological Chemistry"},{"issue":"1","key":"pgen.1011840.ref061","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1093\/jac\/dki171","article-title":"Efflux-mediated antimicrobial resistance","volume":"56","author":"K Poole","year":"2005","journal-title":"J Antimicrob Chemother"},{"issue":"17","key":"pgen.1011840.ref062","doi-asserted-by":"crossref","DOI":"10.1128\/JB.00303-18","article-title":"A Genetic Determinant of Persister Cell Formation in Bacterial Pathogens","volume":"200","author":"DR Cameron","year":"2018","journal-title":"J Bacteriol"},{"issue":"2","key":"pgen.1011840.ref063","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.molcel.2016.03.035","article-title":"Enhanced Efflux Activity Facilitates Drug Tolerance in Dormant Bacterial Cells","volume":"62","author":"Y Pu","year":"2016","journal-title":"Mol Cell"},{"issue":"42","key":"pgen.1011840.ref064","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2405983121","article-title":"Tracking the progeny of bacterial persisters using a CRISPR-based genomic recorder","volume":"121","author":"JA Rycroft","year":"2024","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"7","key":"pgen.1011840.ref065","doi-asserted-by":"crossref","first-page":"4815","DOI":"10.1074\/jbc.M109.073874","article-title":"Gap filling activities of Pseudomonas DNA ligase D (LigD) polymerase and functional interactions of LigD with the DNA end-binding Ku protein","volume":"285","author":"H Zhu","year":"2010","journal-title":"J Biol Chem"},{"issue":"28","key":"pgen.1011840.ref066","doi-asserted-by":"crossref","first-page":"25973","DOI":"10.1074\/jbc.M504002200","article-title":"Novel 3\u2019-ribonuclease and 3\u2019-phosphatase activities of the bacterial non-homologous end-joining protein, DNA ligase D","volume":"280","author":"H Zhu","year":"2005","journal-title":"J Biol Chem"},{"key":"pgen.1011840.ref067","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.01222","article-title":"Engineered proteins detect spontaneous DNA breakage in human and bacterial cells","volume":"2","author":"C Shee","year":"2013","journal-title":"Elife"},{"issue":"6","key":"pgen.1011840.ref068","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1038\/ng2051","article-title":"Spontaneous DNA breakage in single living Escherichia coli cells","volume":"39","author":"JM Pennington","year":"2007","journal-title":"Nat Genet"},{"issue":"50","key":"pgen.1011840.ref069","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.1816606115","article-title":"Phage Mu Gam protein promotes NHEJ in concert with Escherichia coli ligase","volume":"115","author":"S Bhattacharyya","year":"2018","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"pgen.1011840.ref070","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/sj.embor.embor709","article-title":"The Gam protein of bacteriophage Mu is an orthologue of eukaryotic Ku","volume":"4","author":"F d\u2019Adda di Fagagna","year":"2003","journal-title":"EMBO Rep"},{"issue":"9","key":"pgen.1011840.ref071","doi-asserted-by":"crossref","first-page":"4505","DOI":"10.1093\/nar\/gky160","article-title":"Pseudomonas aeruginosa MutL promotes large chromosomal deletions through non-homologous end joining to prevent bacteriophage predation","volume":"46","author":"M Shen","year":"2018","journal-title":"Nucleic Acids Res"},{"issue":"17","key":"pgen.1011840.ref072","doi-asserted-by":"crossref","first-page":"12142","DOI":"10.1016\/S0021-9258(19)49816-5","article-title":"Initiation of methyl-directed mismatch repair.","volume":"267","author":"KG Au","year":"1992","journal-title":"Journal of Biological Chemistry"},{"issue":"6","key":"pgen.1011840.ref073","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1046\/j.1365-2958.2002.02855.x","article-title":"The mismatch repair system (mutS, mutL and uvrD genes) in Pseudomonas aeruginosa: molecular characterization of naturally occurring mutants","volume":"43","author":"A Oliver","year":"2002","journal-title":"Mol Microbiol"},{"key":"pgen.1011840.ref074","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/1471-2199-9-20","article-title":"Use of the lambda Red recombinase system to rapidly generate mutants in Pseudomonas aeruginosa","volume":"9","author":"B Lesic","year":"2008","journal-title":"BMC Mol Biol"},{"issue":"22","key":"pgen.1011840.ref075","doi-asserted-by":"crossref","first-page":"8006","DOI":"10.1073\/pnas.0503005102","article-title":"ExsE, a secreted regulator of type III secretion genes in Pseudomonas aeruginosa","volume":"102","author":"A Rietsch","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pgen.1011840.ref076","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.ymben.2015.06.005","article-title":"An ensemble-guided approach identifies ClpP as a major regulator of transcript levels in nitric oxide-stressed Escherichia coli","volume":"31","author":"JL Robinson","year":"2015","journal-title":"Metab Eng"},{"issue":"29","key":"pgen.1011840.ref077","doi-asserted-by":"crossref","first-page":"12822","DOI":"10.1073\/pnas.1005830107","article-title":"Structure of bacterial LigD 3\u2019-phosphoesterase unveils a DNA repair superfamily","volume":"107","author":"PA Nair","year":"2010","journal-title":"Proc Natl Acad Sci U S A"}],"updated-by":[{"DOI":"10.1371\/journal.pgen.1011840","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T00:00:00Z","timestamp":1757030400000}}],"container-title":["PLOS Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgen.1011840","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T18:04:50Z","timestamp":1757095490000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgen.1011840"}},"subtitle":[],"editor":[{"given":"Danielle A.","family":"Garsin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,9,2]]},"references-count":77,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9,2]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pgen.1011840","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.pgen.1011840","asserted-by":"object"}]},"ISSN":["1553-7404"],"issn-type":[{"value":"1553-7404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,2]]}}}