{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T01:35:07Z","timestamp":1776908107620,"version":"3.51.2"},"reference-count":76,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T00:00:00Z","timestamp":1696377600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"ISCIII","doi-asserted-by":"publisher","award":["MPY 509\/19"],"award-info":[{"award-number":["MPY 509\/19"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"ISCIII","doi-asserted-by":"publisher","award":["PMP22\/00092"],"award-info":[{"award-number":["PMP22\/00092"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["MPY 509\/19"],"award-info":[{"award-number":["MPY 509\/19"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PMP22\/00092"],"award-info":[{"award-number":["PMP22\/00092"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Mutations leading to upregulation of efflux pumps can produce multiple drug resistance in the pathogen Pseudomonas aeruginosa. Changes in their DNA binding regions, i.e., palindromic operators, can compromise pump depression and subsequently enhance resistance against several antibacterials and biocides. Here, we have identified (pseudo)palindromic repeats close to promoters of genes encoding 13 core drug-efflux pumps of P. aeruginosa. This framework was applied to detect mutations in these repeats in 17,292 genomes. Eighty-nine percent of isolates carried at least one mutation. Eight binary genetic properties potentially related to expression were calculated for mutations. These included palindromicity reduction, mutation type, positioning within the repeat and DNA-bending shift. High-risk ST298, ST308 and ST357 clones commonly carried four conserved mutations while ST175 and the cystic fibrosis-linked ST649 clones showed none. Remarkably, a T-to-C transition in the fourth position of the upstream repeat for mexEF-oprN was nearly exclusive of the high-risk ST111 clone. Other mutations were associated with high-risk sublineages using sample geotemporal metadata. Moreover, 1.5% of isolates carried five or more mutations suggesting they undergo an alternative program for regulation of their effluxome. Overall, P. aeruginosa shows a wide range of operator mutations with a potential effect on efflux pump expression and antibiotic resistance.<\/jats:p>","DOI":"10.3390\/microorganisms11102486","type":"journal-article","created":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T07:47:52Z","timestamp":1696405672000},"page":"2486","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Mutation Analysis in Regulator DNA-Binding Regions for Antimicrobial Efflux Pumps in 17,000 Pseudomonas aeruginosa Genomes"],"prefix":"10.3390","volume":"11","author":[{"given":"Mar\u00eda","family":"P\u00e9rez-V\u00e1zquez","sequence":"first","affiliation":[{"name":"Reference and Research Laboratory for Antibiotic Resistance and Health Care Infections, National Centre for Microbiology, Instituto de Salud Carlos III (ISCIII), Majadahonda, 28029 Madrid, Spain"},{"name":"CIBER de Enfermedades Infecciosas (CIBERINFEC), 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carla","family":"L\u00f3pez-Causap\u00e9","sequence":"additional","affiliation":[{"name":"CIBER de Enfermedades Infecciosas (CIBERINFEC), 28029 Madrid, Spain"},{"name":"Microbiology Department-Research Institute Biomedical Islas Baleares (IdISDBa), Hospital Son Espases, 07122 Palma de Mallorca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9s","family":"Corral-Lugo","sequence":"additional","affiliation":[{"name":"Intrahospital Infections Unit, National Centre for Microbiology, ISCIII, Majadahonda, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J.","family":"McConnell","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3327-8263","authenticated-orcid":false,"given":"Jes\u00fas","family":"Oteo-Iglesias","sequence":"additional","affiliation":[{"name":"Reference and Research Laboratory for Antibiotic Resistance and Health Care Infections, National Centre for Microbiology, Instituto de Salud Carlos III (ISCIII), Majadahonda, 28029 Madrid, Spain"},{"name":"CIBER de Enfermedades Infecciosas (CIBERINFEC), 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Oliver","sequence":"additional","affiliation":[{"name":"CIBER de Enfermedades Infecciosas (CIBERINFEC), 28029 Madrid, Spain"},{"name":"Microbiology Department-Research Institute Biomedical Islas Baleares (IdISDBa), Hospital Son Espases, 07122 Palma de Mallorca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio J.","family":"Mart\u00edn-Galiano","sequence":"additional","affiliation":[{"name":"Core Scientific and Technical Units, ISCIII, Majadahonda, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S93","DOI":"10.1086\/514909","article-title":"Resistance Mechanisms in Pseudomonas aeruginosa and Other Nonfermentative Gram-Negative Bacteria","volume":"27","author":"Hancock","year":"1998","journal-title":"Clin. Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Parkins, M.D., Somayaji, R., and Waters, V.J. (2018). Epidemiology, Biology, and Impact of Clonal Pseudomonas aeruginosa Infections in Cystic Fibrosis. Clin. Microbiol. Rev., 31.","DOI":"10.1128\/CMR.00019-18"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Turner, K.H., Everett, J., Trivedi, U., Rumbaugh, K.P., and Whiteley, M. (2014). Requirements for Pseudomonas aeruginosa Acute Burn and Chronic Surgical Wound Infection. PLoS Genet., 10.","DOI":"10.1371\/journal.pgen.1004518"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/S1473-3099(17)30753-3","article-title":"Discovery, Research, and Development of New Antibiotics: The WHO Priority List of Antibiotic-Resistant Bacteria and Tuberculosis","volume":"18","author":"Tacconelli","year":"2018","journal-title":"Lancet Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"159","DOI":"10.2165\/00003495-200464020-00004","article-title":"Efflux-Mediated Drug Resistance in Bacteria","volume":"64","author":"Li","year":"2004","journal-title":"Drugs"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Lorusso, A.B., Carrara, J.A., Barroso, C.D.N., Tuon, F.F., and Faoro, H. (2022). Role of Efflux Pumps on Antimicrobial Resistance in Pseudomonas aeruginosa. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232415779"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1111\/j.1574-6968.2001.tb10794.x","article-title":"Construction of a Series of Mutants Lacking All of the Four Major Mex Operons for Multidrug Efflux Pumps or Possessing Each One of the Operons from Pseudomonas aeruginosa PAO1: MexCD-OprJ Is an Inducible Pump","volume":"202","author":"Morita","year":"2001","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1128\/AAC.48.5.1797-1802.2004","article-title":"Clinical Strains of Pseudomonas aeruginosa Overproducing MexAB-OprM and MexXY Efflux Pumps Simultaneously","volume":"48","author":"Llanes","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1016\/j.str.2016.06.008","article-title":"Mutation-Induced Population Shift in the MexR Conformational Ensemble Disengages DNA Binding: A Novel Mechanism for MarR Family Derepression","volume":"24","author":"Anandapadamanaban","year":"2016","journal-title":"Structure"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4155","DOI":"10.1093\/nar\/gkab213","article-title":"Structures of Neisseria gonorrhoeae MtrR-Operator Complexes Reveal Molecular Mechanisms of DNA Recognition and Antibiotic Resistance-Conferring Clinical Mutations","volume":"49","author":"Beggs","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"L\u00f3pez-Causap\u00e9, C., Cabot, G., Del Barrio-Tofi\u00f1o, E., and Oliver, A. (2018). The Versatile Mutational Resistome of Pseudomonas aeruginosa. Front. Microbiol., 9.","DOI":"10.3389\/fmicb.2018.00685"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"7600","DOI":"10.1128\/JB.00850-07","article-title":"Identification and Characterization of TriABC-OpmH, a Triclosan Efflux Pump of Pseudomonas aeruginosa Requiring Two Membrane Fusion Proteins","volume":"189","author":"Mima","year":"2007","journal-title":"J. Bacteriol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3509","DOI":"10.1099\/mic.0.031260-0","article-title":"Gene Cloning and Characteristics of the RND-Type Multidrug Efflux Pump MuxABC-OpmB Possessing Two RND Components in Pseudomonas aeruginosa","volume":"155","author":"Mima","year":"2009","journal-title":"Microbiology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1111\/j.1348-0421.2002.tb02711.x","article-title":"High-Level Fluoroquinolone Resistance in Pseudomonas aeruginosa Due to Interplay of the MexAB-OprM Efflux Pump and the DNA Gyrase Mutation","volume":"46","author":"Nakajima","year":"2002","journal-title":"Microbiol. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1093\/jac\/dkf185","article-title":"Fitness of in Vitro Selected Pseudomonas aeruginosa NalB and NfxB Multidrug Resistant Mutants","volume":"50","author":"Linares","year":"2002","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Amieva, R., Gil-Gil, T., Mart\u00ednez, J.L., and Alcalde-Rico, M. (2022). The MexJK Multidrug Efflux Pump Is Not Involved in Acquired or Intrinsic Antibiotic Resistance in Pseudomonas aeruginosa, but Modulates the Bacterial Quorum Sensing Response. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23147492"},{"key":"ref_17","first-page":"1729","article-title":"Interaction of Biofilm and Efflux Pump in Clinical Isolates of Carbapenem Resistant P. aeruginosa","volume":"26","author":"Li","year":"2022","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2875","DOI":"10.1093\/nar\/18.10.2875","article-title":"Quantitative Analysis of Tn10 Tet Repressor Binding to a Complete Set of Tet Operator Mutants","volume":"18","author":"Sizemore","year":"1990","journal-title":"Nucleic Acids Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4253","DOI":"10.1093\/nar\/14.10.4253","article-title":"Tn10 Tet Operator Mutations Affecting Tet Repressor Recognition","volume":"14","author":"Wissmann","year":"1986","journal-title":"Nucleic Acids Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"30158","DOI":"10.1074\/jbc.M403343200","article-title":"Definition of a Consensus DNA-Binding Site for PecS, a Global Regulator of Virulence Gene Expression in Erwinia chrysanthemi and Identification of New Members of the PecS Regulon","volume":"279","author":"Rouanet","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/j.jmb.2007.04.022","article-title":"The Transcriptional Repressor TtgV Recognizes a Complex Operator as a Tetramer and Induces Convex DNA Bending","volume":"369","author":"Guazzaroni","year":"2007","journal-title":"J. Mol. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1128\/JB.02558-14","article-title":"Mutations within the MepA Operator Affect Binding of the MepR Regulatory Protein and Its Induction by MepA Substrates in Staphylococcus aureus","volume":"197","author":"Schindler","year":"2015","journal-title":"J. Bacteriol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5756","DOI":"10.1128\/jb.177.20.5756-5761.1995","article-title":"Role of Curved DNA in Binding of Escherichia Coli RNA Polymerase to Promoters","volume":"177","author":"Nickerson","year":"1995","journal-title":"J. Bacteriol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1128\/mr.58.2.268-290.1994","article-title":"Promoters Responsive to DNA Bending: A Common Theme in Prokaryotic Gene Expression","volume":"58","author":"Rojo","year":"1994","journal-title":"Microbiol. Rev."},{"key":"ref_25","first-page":"D517","article-title":"CARD 2020: Antibiotic Resistome Surveillance with the Comprehensive Antibiotic Resistance Database","volume":"48","author":"Alcock","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1128\/AAC.01310-13","article-title":"ARG-ANNOT, a New Bioinformatic Tool to Discover Antibiotic Resistance Genes in Bacterial Genomes","volume":"58","author":"Gupta","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3491","DOI":"10.1093\/jac\/dkaa345","article-title":"ResFinder 4.0 for Predictions of Phenotypes from Genotypes","volume":"75","author":"Bortolaia","year":"2020","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_28","first-page":"e00050","article-title":"SSTAR, a Stand-Alone Easy-To-Use Antimicrobial Resistance Gene Predictor","volume":"1","author":"Limbago","year":"2016","journal-title":"mSphere"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/nyas.13358","article-title":"Genomics of Antibiotic-Resistance Prediction in Pseudomonas aeruginosa","volume":"1435","author":"Jeukens","year":"2019","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1016\/j.ijantimicag.2016.09.012","article-title":"High-Level Resistance to Meropenem in Clinical Isolates of Pseudomonas aeruginosa in the Absence of Carbapenemases: Role of Active Efflux and Porin Alterations","volume":"48","author":"Chalhoub","year":"2016","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_31","first-page":"356","article-title":"Sequencing-Based Methods and Resources to Study Antimicrobial Resistance","volume":"20","author":"Boolchandani","year":"2019","journal-title":"Nat. Rev. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Jeukens, J., Kukavica-Ibrulj, I., Emond-Rheault, J.G., Freschi, L., and Levesque, R.C. (2017). Comparative Genomics of a Drug-Resistant Pseudomonas aeruginosa Panel and the Challenges of Antimicrobial Resistance Prediction from Genomes. FEMS Microbiol. Lett., 364.","DOI":"10.1093\/femsle\/fnx161"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1128\/CMR.00117-14","article-title":"The Challenge of Efflux-Mediated Antibiotic Resistance in Gram-Negative Bacteria","volume":"28","author":"Li","year":"2015","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3099","DOI":"10.1093\/jac\/dkaa257","article-title":"Large-Scale Assessment of Antimicrobial Resistance Marker Databases for Genetic Phenotype Prediction: A Systematic Review","volume":"75","author":"Mahfouz","year":"2020","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1038\/35023079","article-title":"Complete Genome Sequence of Pseudomonas aeruginosa PAO1, an Opportunistic Pathogen","volume":"406","author":"Stover","year":"2000","journal-title":"Nature"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"D646","DOI":"10.1093\/nar\/gkv1227","article-title":"Enhanced Annotations and Features for Comparing Thousands of Pseudomonas Genomes in the Pseudomonas Genome Database","volume":"44","author":"Winsor","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"D73","DOI":"10.1093\/nar\/gkv1226","article-title":"Assembly: A Resource for Assembled Genomes at NCBI","volume":"44","author":"Kitts","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"D459","DOI":"10.1093\/nar\/gkn757","article-title":"DOOR: A Database for Prokaryotic Operons","volume":"37","author":"Mao","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Kingsford, C.L., Ayanbule, K., and Salzberg, S.L. (2007). Rapid, Accurate, Computational Discovery of Rho-Independent Transcription Terminators Illuminates Their Relationship to DNA Uptake. Genome Biol., 8.","DOI":"10.1186\/gb-2007-8-2-r22"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Coppens, L., and Lavigne, R. (2020). SAPPHIRE: A Neural Network Based Classifier for \u03a370 Promoter Prediction in Pseudomonas. BMC Bioinform., 21.","DOI":"10.1186\/s12859-020-03730-z"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3099","DOI":"10.1093\/bioinformatics\/btl551","article-title":"Pattern Locator: A New Tool for Finding Local Sequence Patterns in Genomic DNA Sequences","volume":"22","author":"Mrazek","year":"2006","journal-title":"Bioinformatics"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/S0168-9525(00)02024-2","article-title":"EMBOSS: The European Molecular Biology Open Software Suite","volume":"16","author":"Rice","year":"2000","journal-title":"Trends Genet."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0022-2836(05)80360-2","article-title":"Basic Local Alignment Search Tool","volume":"215","author":"Altschul","year":"1990","journal-title":"J. Mol. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3150","DOI":"10.1093\/bioinformatics\/bts565","article-title":"CD-HIT: Accelerated for Clustering the next-Generation Sequencing Data","volume":"28","author":"Fu","year":"2012","journal-title":"Bioinformatics"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1002\/pro.3290","article-title":"Clustal Omega for Making Accurate Alignments of Many Protein Sequences","volume":"27","author":"Sievers","year":"2018","journal-title":"Protein Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3686","DOI":"10.1093\/nar\/gkg559","article-title":"DNA Analysis Servers: Plot.It, Bend.It, Model.It and IS","volume":"31","author":"Vlahovicek","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Hyatt, D., Chen, G.-L., Locascio, P.F., Land, M.L., Larimer, F.W., and Hauser, L.J. (2010). Prodigal: Prokaryotic Gene Recognition and Translation Initiation Site Identification. BMC Bioinform., 11.","DOI":"10.1186\/1471-2105-11-119"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2856","DOI":"10.1093\/bioinformatics\/bty1057","article-title":"MMseqs2 Desktop and Local Web Server App for Fast, Interactive Sequence Searches","volume":"35","author":"Mirdita","year":"2019","journal-title":"Bioinformatics"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"D690","DOI":"10.1093\/nar\/gkac920","article-title":"CARD 2023: Expanded Curation, Support for Machine Learning, and Resistome Prediction at the Comprehensive Antibiotic Resistance Database","volume":"51","author":"Alcock","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"124","DOI":"10.12688\/wellcomeopenres.14826.1","article-title":"Open-Access Bacterial Population Genomics: BIGSdb Software, the PubMLST.Org Website and Their Applications","volume":"3","author":"Jolley","year":"2018","journal-title":"Wellcome Open Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3691","DOI":"10.1093\/bioinformatics\/btv421","article-title":"Roary: Rapid Large-Scale Prokaryote Pan Genome Analysis","volume":"31","author":"Page","year":"2015","journal-title":"Bioinformatics"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2688","DOI":"10.1093\/bioinformatics\/btl446","article-title":"RAxML-VI-HPC: Maximum Likelihood-Based Phylogenetic Analyses with Thousands of Taxa and Mixed Models","volume":"22","author":"Stamatakis","year":"2006","journal-title":"Bioinformatics"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"W242","DOI":"10.1093\/nar\/gkw290","article-title":"Interactive Tree of Life (ITOL) v3: An Online Tool for the Display and Annotation of Phylogenetic and Other Trees","volume":"44","author":"Letunic","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"T\u00f6nnies, H., Prior, K., Harmsen, D., and Mellmann, A. (2021). Establishment and Evaluation of a Core Genome Multilocus Sequence Typing Scheme for Whole-Genome Sequence-Based Typing of Pseudomonas aeruginosa. J. Clin. Microbiol., 59.","DOI":"10.1128\/JCM.01987-20"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1128\/JB.183.3.807-812.2001","article-title":"MexR Repressor of the MexAB-OprM Multidrug Efflux Operon of Pseudomonas aeruginosa: Identification of MexR Binding Sites in the MexA-MexR Intergenic Region","volume":"183","author":"Evans","year":"2001","journal-title":"J. Bacteriol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"D295","DOI":"10.1093\/nar\/gkab1110","article-title":"PRODORIC: State-of-the-Art Database of Prokaryotic Gene Regulation","volume":"50","author":"Dudek","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Cipriano, M.J., Novichkov, P.N., Kazakov, A.E., Rodionov, D.A., Arkin, A.P., Gelfand, M.S., and Dubchak, I. (2013). RegTransBase--a Database of Regulatory Sequences and Interactions Based on Literature: A Resource for Investigating Transcriptional Regulation in Prokaryotes. BMC Genom., 14.","DOI":"10.1186\/1471-2164-14-213"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Halachev, M.R., Loman, N.J., and Pallen, M.J. (2011). Calculating Orthologs in Bacteria and Archaea: A Divide and Conquer Approach. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0028388"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"106196","DOI":"10.1016\/j.ijantimicag.2020.106196","article-title":"Pseudomonas Aeruginosa Epidemic High-Risk Clones and Their Association with Horizontally-Acquired \u03b2-Lactamases: 2020 Update","volume":"56","author":"Oliver","year":"2020","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1128\/AAC.03954-14","article-title":"The Resistome of Pseudomonas aeruginosa in Relationship to Phenotypic Susceptibility","volume":"59","author":"Kos","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Amsalu, A., Sapula, S.A., De Barros Lopes, M., Hart, B.J., Nguyen, A.H., Drigo, B., Turnidge, J., Leong, L.E., and Venter, H. (2020). Efflux Pump-Driven Antibiotic and Biocide Cross-Resistance in Pseudomonas aeruginosa Isolated from Different Ecological Niches: A Case Study in the Development of Multidrug Resistance in Environmental Hotspots. Microorganisms, 8.","DOI":"10.3390\/microorganisms8111647"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.drup.2015.08.002","article-title":"The Increasing Threat of Pseudomonas aeruginosa High-Risk Clones","volume":"21\u201322","author":"Oliver","year":"2015","journal-title":"Drug Resist. Updat."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Kidd, T.J., Ritchie, S.R., Ramsay, K.A., Grimwood, K., Bell, S.C., and Rainey, P.B. (2012). Pseudomonas aeruginosa Exhibits Frequent Recombination, but Only a Limited Association between Genotype and Ecological Setting. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0044199"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/ng.3148","article-title":"Convergent Evolution and Adaptation of Pseudomonas aeruginosa within Patients with Cystic Fibrosis","volume":"47","author":"Marvig","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1080\/22221751.2021.1894903","article-title":"An IncP-2 Plasmid Sublineage Associated with Dissemination of Bla(IMP-45) among Carbapenem-Resistant Pseudomonas aeruginosa","volume":"10","author":"Zhang","year":"2021","journal-title":"Emerg. Microbes Infect."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"5676","DOI":"10.1128\/AAC.00101-11","article-title":"Role of the MexEF-OprN Efflux System in Low-Level Resistance of Pseudomonas aeruginosa to Ciprofloxacin","volume":"55","author":"Llanes","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1093\/jac\/48.4.549","article-title":"Fluoroquinolone Susceptibilities of Efflux-Mediated Multidrug-Resistant Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Burkholderia cepacia","volume":"48","author":"Zhang","year":"2001","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Green, A.E., Am\u00e9zquita, A., Le Marc, Y., Bull, M.J., Connor, T.R., and Mahenthiralingam, E. (2018). The Consistent Differential Expression of Genetic Pathways Following Exposure of an Industrial Pseudomonas aeruginosa Strain to Preservatives and a Laundry Detergent Formulation. FEMS Microbiol. Lett., 365.","DOI":"10.1093\/femsle\/fny062"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"111296","DOI":"10.1016\/j.envres.2021.111296","article-title":"Chlorine Disinfectants Promote Microbial Resistance in Pseudomonas Sp","volume":"199","author":"Tong","year":"2021","journal-title":"Environ. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1093\/jac\/dkg390","article-title":"A New Member of the Tripartite Multidrug Efflux Pumps, MexVW-OprM, in Pseudomonas aeruginosa","volume":"52","author":"Li","year":"2003","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1111\/j.1574-6968.2010.02063.x","article-title":"Transcriptional Regulation of the MexEF-OprN Multidrug Efflux Pump Operon by MexT and an Unidentified Repressor in NfxC-Type Mutant of Pseudomonas aeruginosa","volume":"311","author":"Maseda","year":"2010","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Morita, Y., Tomida, J., and Kawamura, Y. (2014). Responses of Pseudomonas Aeruginosa to Antimicrobials. Front. Microbiol., 4.","DOI":"10.3389\/fmicb.2013.00422"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1093\/jac\/dky083","article-title":"Diversity of Mutations in Regulatory Genes of Resistance-Nodulation-Cell Division Efflux Pumps in Association with Tigecycline Resistance in Acinetobacter baumannii","volume":"73","author":"Gerson","year":"2018","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1128\/JB.01165-08","article-title":"MtrR Modulates RpoH Expression and Levels of Antimicrobial Resistance in Neisseria gonorrhoeae","volume":"191","author":"Folster","year":"2009","journal-title":"J. Bacteriol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e02114","DOI":"10.1128\/AAC.02114-16","article-title":"PA3225 Is a Transcriptional Repressor of Antibiotic Resistance Mechanisms in Pseudomonas aeruginosa","volume":"61","author":"Hall","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Langendonk, R.F., Neill, D.R., and Fothergill, J.L. (2021). The Building Blocks of Antimicrobial Resistance in Pseudomonas aeruginosa: Implications for Current Resistance-Breaking Therapies. Front. Cell Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.665759"}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/11\/10\/2486\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:04:56Z","timestamp":1760130296000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/11\/10\/2486"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,4]]},"references-count":76,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["microorganisms11102486"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms11102486","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,4]]}}}