{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:41:19Z","timestamp":1790775679183,"version":"4.1.0"},"reference-count":43,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,8,4]],"date-time":"2020-08-04T00:00:00Z","timestamp":1596499200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/04378\/2020"],"award-info":[{"award-number":["UIDB\/04378\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>The ciprofloxacin-modifying crpP gene was recently identified in a plasmid isolated from a Pseudomonas aeruginosa clinical isolate. Homologues of this gene were also identified in Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii. We set out to explore the mobile elements involved in the acquisition and spread of this gene in publicly available and complete genomes of Pseudomonas spp. All Pseudomonas complete genomes were downloaded from NCBI\u2019s Refseq library and were inspected for the presence of the crpP gene. The mobile elements carrying this gene were further characterized. The crpP gene was identified only in P. aeruginosa, in more than half of the complete chromosomes (61.9%, n = 133\/215) belonging to 52 sequence types, of which the high-risk clone ST111 was the most frequent. We identified 136 crpP-harboring integrative and conjugative elements (ICEs), with 93.4% belonging to the mating-pair formation G (MPFG) family. The ICEs were integrated at the end of a tRNALys gene and were all flanked by highly conserved 45-bp direct repeats. The crpP-carrying ICEs contain 26 core genes (2.2% of all 1193 genes found in all the ICEs together), which are present in 99% or more of the crpP-harboring ICEs. The most frequently encoded traits on these ICEs include replication, transcription, intracellular trafficking and cell motility. Our work suggests that ICEs are the main vectors promoting the dissemination of the ciprofloxacin-modifying crpP gene in P. aeruginosa.<\/jats:p>","DOI":"10.3390\/genes11080889","type":"journal-article","created":{"date-parts":[[2020,8,4]],"date-time":"2020-08-04T10:45:17Z","timestamp":1596537917000},"page":"889","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["ICEs Are the Main Reservoirs of the Ciprofloxacin-Modifying crpP Gene in Pseudomonas aeruginosa"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2771-2345","authenticated-orcid":false,"given":"Jo\u00e3o","family":"Botelho","sequence":"first","affiliation":[{"name":"Antibiotic Resistance Evolution Group, Max-Planck-Institute for Evolutionary Biology, 24306 Pl\u00f6n, Germany"},{"name":"Department of Evolutionary Ecology and Genetics, Zoological Institute, Christian-Albrechts-Universit\u00e4t zu Kiel, 24118 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filipa","family":"Grosso","sequence":"additional","affiliation":[{"name":"UCIBIO\/REQUIMTE, Laborat\u00f3rio de Microbiologia, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu\u00edsa","family":"Peixe","sequence":"additional","affiliation":[{"name":"UCIBIO\/REQUIMTE, Laborat\u00f3rio de Microbiologia, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"De Oliveira, D.M.P., Forde, B.M., Kidd, T.J., Harris, P.N.A., Schembri, M.A., Beatson, S.A., Paterson, D.L., and Walker, M.J. (2020). Antimicrobial resistance in ESKAPE pathogens. Clin. Microbiol. Rev., 33.","DOI":"10.1128\/CMR.00181-19"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Botelho, J., Grosso, F., and Peixe, L. (2019). Antibiotic resistance in Pseudomonas aeruginosa \u2013 Mechanisms, epidemiology and evolution. Drug Resist. Updat., 44.","DOI":"10.1016\/j.drup.2019.07.002"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1007\/s10096-017-2907-x","article-title":"Antimicrobial combination treatment including ciprofloxacin decreased the mortality rate of Pseudomonas aeruginosa bacteraemia: A retrospective cohort study","volume":"36","author":"Paulsson","year":"2017","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Klodzi\u0144ska, S.N., Priemel, P.A., Rades, T., and Nielsen, H.M. (2016). Inhalable antimicrobials for treatment of bacterial biofilm-associated sinusitis in cystic fibrosis patients: Challenges and drug delivery approaches. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17101688"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1136\/thorax.58.9.794","article-title":"Survey of resistance of Pseudomonas aeruginosa from UK patients with cystic fibrosis to six commonly prescribed antimicrobial agents","volume":"58","author":"Pitt","year":"2003","journal-title":"Thorax"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1099\/jmm.0.000873","article-title":"Mechanisms of ciprofloxacin resistance in Pseudomonas aeruginosa: New approaches to an old problem","volume":"68","author":"Rehman","year":"2019","journal-title":"J. Med. Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1128\/AAC.01581-12","article-title":"Quantitative contributions of target alteration and decreased drug accumulation to Pseudomonas aeruginosa fluoroquinolone resistance","volume":"57","author":"Bruchmann","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.coph.2011.07.007","article-title":"Co-resistance: An opportunity for the bacteria and resistance genes","volume":"11","year":"2011","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2237","DOI":"10.1093\/jac\/dkv103","article-title":"Description of an original integron encompassing blaVIM-2, qnrVC1 and genes encoding bacterial group II intron proteins in Pseudomonas aeruginosa","volume":"70","author":"Belotti","year":"2015","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Ruiz, J. (2019). Transferable mechanisms of quinolone resistance from 1998 onward. Clin. Microbiol. Rev., 32.","DOI":"10.1128\/CMR.00007-19"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Ch\u00e1vez-Jacobo, V.M., Hern\u00e1ndez-Ram\u00edrez, K.C., Romo-Rodr\u00edguez, P., P\u00e9rez-Gallardo, R.V., Campos-Garc\u00eda, J., F\u00e9lix Guti\u00e9rrez-Corona, J., Garc\u00eda-Merinos, J.P., Meza-Carmen, V., Silva-S\u00e1nchez, J., and Ram\u00edrez-D\u00edaz, M.I. (2018). CrpP is a novel ciprofloxacin-modifying enzyme encoded by the Pseudomonas aeruginosa pUM505 plasmid. Antimicrob. Agents Chemother., 62.","DOI":"10.1128\/AAC.02629-17"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Ruiz, J. (2019). CrpP, a passenger or a hidden stowaway in the Pseudomonas aeruginosa genome?. J. Antimicrob. Chemother.","DOI":"10.1093\/jac\/dkz316"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1093\/jac\/dky562","article-title":"Prevalence of the crpP gene conferring decreased ciprofloxacin susceptibility in enterobacterial clinical isolates from Mexican hospitals","volume":"74","author":"Cervantes","year":"2019","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_14","unstructured":"Pablo, J., Merinos, G., L\u00f3pez, Y., Meza, V., and Ram\u00edrez, M.I. (2020). Identification of Essential Residues for Ciprofloxacin Resistance of Ciprofloxacin\u2014Modifying Enzyme ( CrpP ) of pUM505. Microbiology."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Partridge, S.R., Kwong, S.M., Firth, N., and Jensen, S.O. (2018). Mobile genetic elements associated with antimicrobial resistance. Clin. Microbiol. Rev., 31.","DOI":"10.1128\/CMR.00088-17"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Botelho, J., Roberts, A.P., Le\u00f3n-Sampedro, R., Grosso, F., and Peixe, L. (2018). Carbapenemases on the move: It\u2019s good to be on ICEs. Mob. DNA, 9.","DOI":"10.1186\/s13100-018-0141-4"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Guglielmini, J., Quintais, L., Garcill\u00e1n-Barcia, M.P., de la Cruz, F., and Rocha, E.P.C. (2011). The repertoire of ICE in prokaryotes underscores the unity, diversity, and ubiquity of conjugation. PLoS Genet., 7.","DOI":"10.1371\/journal.pgen.1002222"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Botelho, J., and Schulenburg, H. (2020). The role of integrative and conjugative elements in antibiotic resistance evolution. Trends Microbiol.","DOI":"10.1016\/j.tim.2020.05.011"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Liu, M., Li, X., Xie, Y., Bi, D., Sun, J., Li, J., Tai, C., Deng, Z., and Ou, H.-Y. (2018). ICEberg 2.0: An updated database of bacterial integrative and conjugative elements. Nucleic Acids Res.","DOI":"10.1093\/nar\/gky1123"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5715","DOI":"10.1093\/nar\/gku194","article-title":"Key components of the eight classes of type IV secretion systems involved in bacterial conjugation or protein secretion","volume":"42","author":"Guglielmini","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Jolley, K.A., Bray, J.E., and Maiden, M.C.J. (2018). Open-access bacterial population genomics: BIGSdb software, the PubMLST.org website and their applications. Wellcome Open Res., 3.","DOI":"10.12688\/wellcomeopenres.14826.1"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1093\/bioinformatics\/btu153","article-title":"Prokka: Rapid prokaryotic genome annotation","volume":"30","author":"Seemann","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_23","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_24","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1093\/molbev\/msp077","article-title":"FastTree: Computing large minimum evolution trees with profiles instead of a distance matrix","volume":"26","author":"Price","year":"2009","journal-title":"Mol. Biol. Evol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"W256","DOI":"10.1093\/nar\/gkz239","article-title":"Interactive Tree Of Life (iTOL) v4: Recent updates and new developments","volume":"47","author":"Letunic","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"D309","DOI":"10.1093\/nar\/gky1085","article-title":"eggNOG 5.0: A hierarchical, functionally and phylogenetically annotated orthology resource based on 5090 organisms and 2502 viruses","volume":"47","author":"Szklarczyk","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"W30","DOI":"10.1093\/nar\/gkx343","article-title":"IslandViewer 4: Expanded prediction of genomic islands for larger-scale datasets","volume":"45","author":"Bertelli","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Feldgarden, M., Brover, V., Haft, D.H., Prasad, A.B., Slotta, D.J., Tolstoy, I., Tyson, G.H., Zhao, S., Hsu, C.-H., and McDermott, P.F. (2019). Validating the AMRFinder tool and resistance gene database by using antimicrobial resistance genotype-phenotype correlations in a collection of isolates. Antimicrob. Agents Chemother., 63.","DOI":"10.1128\/AAC.00483-19"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Jain, C., Rodriguez-R, L.M., Phillippy, A.M., Konstantinidis, K.T., and Aluru, S. (2018). High throughput ANI analysis of 90K prokaryotic genomes reveals clear species boundaries. Nat. Commun., 9.","DOI":"10.1038\/s41467-018-07641-9"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"W81","DOI":"10.1093\/nar\/gkz310","article-title":"antiSMASH 5.0: Updates to the secondary metabolite genome mining pipeline","volume":"47","author":"Blin","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"W278","DOI":"10.1093\/nar\/gky383","article-title":"BAGEL4: A user-friendly web server to thoroughly mine RiPPs and bacteriocins","volume":"46","author":"Song","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Abby, S.S., Cury, J., Guglielmini, J., N\u00e9ron, B., Touchon, M., and Rocha, E.P.C. (2016). Identification of protein secretion systems in bacterial genomes. Sci. Rep., 6.","DOI":"10.1038\/srep23080"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Abby, S.S., N\u00e9ron, B., M\u00e9nager, H., Touchon, M., and Rocha, E.P.C. (2014). MacSyFinder: A program to mine genomes for molecular systems with an application to CRISPR-Cas systems. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0110726"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/978-1-4939-9877-7_21","article-title":"MOBscan: Automated annotation of MOB relaxases","volume":"2075","author":"Vielva","year":"2020","journal-title":"Methods Mol. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"W246","DOI":"10.1093\/nar\/gky425","article-title":"CRISPRCasFinder, an update of CRISRFinder, includes a portable version, enhanced performance and integrates search for Cas proteins","volume":"46","author":"Couvin","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_36","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","author":"Oliver","year":"2015","journal-title":"Drug Resist. Updat."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"13950","DOI":"10.1073\/pnas.0506758102","article-title":"Genome analysis of multiple pathogenic isolates of Streptococcus agalactiae: Implications for the microbial \u201cpan-genome\u201d","volume":"102","author":"Tettelin","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3354","DOI":"10.1016\/j.febslet.2010.06.021","article-title":"A predicted S-type pyocin shows a bactericidal activity against clinical Pseudomonas aeruginosa isolates through membrane damage","volume":"584","author":"Ling","year":"2010","journal-title":"FEBS Lett."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1099\/mic.0.070672-0","article-title":"Pore-forming pyocin S5 utilizes the FptA ferripyochelin receptor to kill Pseudomonas aeruginosa","volume":"160","author":"Elfarash","year":"2014","journal-title":"Microbiology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1101\/gr.115592.110","article-title":"Directed networks reveal genomic barriers and DNA repair bypasses to lateral gene transfer among prokaryotes","volume":"21","author":"Popa","year":"2011","journal-title":"Genome Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"8943","DOI":"10.1093\/nar\/gkx607","article-title":"Integrative and conjugative elements and their hosts: Composition, distribution and organization","volume":"45","author":"Cury","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Ortiz de la Rosa, J.M., Nordmann, P., and Poirel, L. (2020). PAGI-associated CrpP-like fluoroquinolone-modifying enzymes among Pseudomonas aeruginosa clinical isolates in Europe. Antimicrob. Agents Chemother.","DOI":"10.1128\/AAC.00489-20"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1128\/MMBR.00027-10","article-title":"The accessory genome of Pseudomonas aeruginosa","volume":"74","author":"Kung","year":"2010","journal-title":"Microbiol. Mol. Biol. Rev."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/11\/8\/889\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:54:18Z","timestamp":1760176458000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/11\/8\/889"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,4]]},"references-count":43,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2020,8]]}},"alternative-id":["genes11080889"],"URL":"https:\/\/doi.org\/10.3390\/genes11080889","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.03.13.991208","asserted-by":"object"}]},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,4]]}}}