{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:55:31Z","timestamp":1790470531321,"version":"4.1.0"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,28]],"date-time":"2022-03-28T00:00:00Z","timestamp":1648425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006282","name":"Koning Boudewijnstichting","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006282","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005564","name":"Gilead Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005564","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>\n                    <jats:italic>Achromobacter<\/jats:italic>\n                    genus (including\n                    <jats:italic>Achromobacter xylosoxidans<\/jats:italic>\n                    , the most prevalent\n                    <jats:italic>Achromobacter<\/jats:italic>\n                    species in patients with cystic fibrosis) is poorly susceptible to most conventional antibiotics. Contribution of efflux by AxyABM, AxyXY-OprZ, and AxyEF-OprN and of target mutations were studied in clinical isolates of\n                    <jats:italic>A. xylosoxidans<\/jats:italic>\n                    and\n                    <jats:italic>Achromobacter insuavis.<\/jats:italic>\n                    Forty-one isolates longitudinally collected from 21 patients with CF were studied by whole-genome sequencing (WGS)-typing, determination of minimum inhibitory concentrations (MICs) of \u03b2-lactams, aminoglycosides, colistin, azithromycin, ciprofloxacin, chloramphenicol, and doxycycline, and expression (quantitative RT-PCR) and function (measure of the uptake of a fluorescent substrate) of efflux pumps. WGS-based typing resulted in 10 clusters comprising 2 or 3 isolates and 20 singletons. The efflux activity was high in strains with elevated MICs for amikacin or azithromycin. This work sheds a new light on the impact of efflux and target mutations in resistance of\n                    <jats:italic>Achromobacter<\/jats:italic>\n                    to several drugs.\n                  <\/jats:p>","DOI":"10.3389\/fmicb.2022.762307","type":"journal-article","created":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T21:51:57Z","timestamp":1648590717000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["Role of Efflux in Antibiotic Resistance of Achromobacter xylosoxidans and Achromobacter insuavis Isolates From Patients With Cystic Fibrosis"],"prefix":"10.3389","volume":"13","author":[{"given":"Hussein","family":"Chalhoub","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Kampmeier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara C.","family":"Kahl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7oise","family":"Van Bambeke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1016\/j.jcf.2015.12.009","article-title":"Distribution of the species of Achromobacter in a French Cystic Fibrosis Centre and multilocus sequence typing analysis reveal the predominance of A. xylosoxidans and clonal relationships between some clinical and environmental isolates.","volume":"15","author":"Amoureux","year":"2016","journal-title":"J. Cyst. Fibros."},{"key":"B2","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1016\/j.jcf.2012.08.005","article-title":"Epidemiology and resistance of Achromobacter xylosoxidans from cystic fibrosis patients in Dijon, Burgundy: first French data.","volume":"12","author":"Amoureux","year":"2013","journal-title":"J. Cyst. Fibros."},{"key":"B3","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1128\/AAC.01243-12","article-title":"Innate aminoglycoside resistance of Achromobacter xylosoxidans is due to AxyXY-OprZ, an RND-type multidrug efflux pump.","volume":"57","author":"Bador","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"B4","doi-asserted-by":"publisher","first-page":"4912","DOI":"10.1128\/AAC.00341-11","article-title":"First description of an RND-type multidrug efflux pump in Achromobacter xylosoxidans, AxyABM.","volume":"55","author":"Bador","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.nmni.2015.11.013","article-title":"Distribution of innate efflux-mediated aminoglycoside resistance among different Achromobacter species.","volume":"10","author":"Bador","year":"2016","journal-title":"New Microbes. New Infect."},{"key":"B6","doi-asserted-by":"publisher","first-page":"868","DOI":"10.1128\/AAC.43.4.868","article-title":"Impact of gyrA and parC mutations on quinolone resistance, doubling time, and supercoiling degree of Escherichia coli.","volume":"43","author":"Bagel","year":"1999","journal-title":"Antimicrob. Agents Chemother."},{"key":"B7","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1111\/j.1365-2958.1994.tb01297.x","article-title":"Neisseria gonorrhoeae acquires mutations in analogous regions of gyrA and parC in fluoroquinolone-resistant isolates.","volume":"14","author":"Belland","year":"1994","journal-title":"Mol. Microbiol."},{"key":"B8","doi-asserted-by":"publisher","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":"B9","doi-asserted-by":"publisher","first-page":"4196","DOI":"10.1128\/AAC.00827-07","article-title":"Capability of 11 antipneumococcal antibiotics to select for resistance by multistep and single-step methodologies.","volume":"51","author":"Clark","year":"2007","journal-title":"Antimicrob. Agents Chemother."},{"key":"B10","year":"2020","journal-title":"Performance Standards for Antimicrobial Susceptibility Testing; 30th Informational Supplement. CLSI document M100-S30."},{"key":"B11","doi-asserted-by":"publisher","first-page":"e2142","DOI":"10.1128\/AAC.02142-19","article-title":"Hypermutator Pseudomonas aeruginosa Exploits Multiple Genetic Pathways To Develop Multidrug Resistance during Long-Term Infections in the Airways of Cystic Fibrosis Patients.","volume":"64","author":"Colque","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"B12","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1080\/00325481.2017.1285677","article-title":"Immunomodulatory indications of azithromycin in respiratory disease: a concise review for the clinician.","volume":"129","author":"Cramer","year":"2017","journal-title":"Postgrad. Med."},{"key":"B13","year":"2020","journal-title":"2019 Patient Registry Annual Data Report."},{"key":"B14","doi-asserted-by":"publisher","first-page":"3788","DOI":"10.1128\/JCM.01946-15","article-title":"Core Genome Multilocus Sequence Typing Scheme for High- Resolution Typing of Enterococcus faecium.","volume":"53","author":"de Been","year":"2015","journal-title":"J. Clin. Microbiol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"2850","DOI":"10.1128\/JCM.01714-16","article-title":"Next-Generation Epidemiology: Using Real-Time Core Genome Multilocus Sequence Typing To Support Infection Control Policy.","volume":"54","author":"Dekker","year":"2016","journal-title":"J. Clin. Microbiol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1952","DOI":"10.1128\/AAC.01463-07","article-title":"Characterization of a naturally occurring class D beta-lactamase from Achromobacter xylosoxidans.","volume":"52","author":"Doi","year":"2008","journal-title":"Antimicrob. Agents Chemother."},{"key":"B17","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1093\/clinids\/23.3.569","article-title":"Achromobacter xylosoxidans bacteremia: report of four cases and review of the literature.","volume":"23","author":"Duggan","year":"1996","journal-title":"Clin. Infect. Dis."},{"key":"B18","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1128\/JCM.01843-16","article-title":"Impact of High Diversity of Achromobacter Populations within Cystic Fibrosis Sputum Samples on Antimicrobial Susceptibility Testing.","volume":"55","author":"Dupont","year":"2017","journal-title":"J. Clin. Microbiol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"2074","DOI":"10.1128\/JCM.02556-16","article-title":"Prevalence and Outcomes of Achromobacter Species Infections in Adults with Cystic Fibrosis: a North American Cohort Study.","volume":"55","author":"Edwards","year":"2017","journal-title":"J. Clin. Microbiol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"3755","DOI":"10.1128\/jb.00690-12","article-title":"Draft genome sequence of Pseudomonas aeruginosa strain ATCC 27853.","volume":"194","author":"Fang","year":"2012","journal-title":"J. Bacteriol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1111\/apm.12896","article-title":"Replicon typing of plasmids in environmental Achromobacter sp. producing quinolone-resistant determinants.","volume":"126","author":"Furlan","year":"2018","journal-title":"APMIS"},{"key":"B22","doi-asserted-by":"publisher","first-page":"a025395","DOI":"10.1101\/cshperspect.a025395","article-title":"Resistance to Macrolide Antibiotics in Public Health Pathogens.","volume":"6","author":"Fyfe","year":"2016","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"B23","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1099\/jmm.0.000499","article-title":"Prevalence and species distribution of Achromobacter sp. cultured from cystic fibrosis patients attending the Aarhus centre in Denmark.","volume":"66","author":"Gade","year":"2017","journal-title":"J. Med. Microbiol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1016\/j.resmic.2018.05.001","article-title":"Phage therapy against Achromobacter xylosoxidans lung infection in a patient with cystic fibrosis: a case report.","volume":"169","author":"Hoyle","year":"2018","journal-title":"Res. Microbiol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1152","DOI":"10.1128\/AAC.04260-14","article-title":"Genomic insights into intrinsic and acquired drug resistance mechanisms in Achromobacter xylosoxidans.","volume":"59","author":"Hu","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"B26","doi-asserted-by":"publisher","first-page":"e1025","DOI":"10.1128\/AAC.01025-20","article-title":"Achromobacter Infections and Treatment Options.","volume":"64","author":"Isler","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"B27","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1128\/AAC.01389-07","article-title":"In vitro capability of faropenem to select for resistant mutants of Streptococcus pneumoniae and Haemophilus influenzae.","volume":"52","author":"Kosowska-Shick","year":"2008","journal-title":"Antimicrob. Agents Chemother."},{"key":"B28","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1128\/AAC.45.1.105-116.2001","article-title":"Identification and characterization of inhibitors of multidrug resistance efflux pumps in Pseudomonas aeruginosa: novel agents for combination therapy.","volume":"45","author":"Lomovskaya","year":"2001","journal-title":"Antimicrob. Agents Chemother."},{"key":"B29","doi-asserted-by":"publisher","first-page":"dkab479","DOI":"10.1093\/jac\/dkab479","article-title":"Role of AxyABM overexpression in acquired resistance in Achromobacter xylosoxidans.","volume":"13","author":"Magallon","year":"2022","journal-title":"J. Antimicrob. Chemother"},{"key":"B30","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1093\/jac\/dkaa440","article-title":"Fluoroquinolone resistance in Achromobacter spp.: substitutions in QRDRs of GyrA, GyrB, ParC and ParE and implication of the RND efflux system AxyEF-OprN.","volume":"76","author":"Magallon","year":"2021","journal-title":"J. Antimicrob. Chemother."},{"key":"B31","doi-asserted-by":"publisher","first-page":"00076","DOI":"10.1183\/23120541.00076-2021","article-title":"Achromobacter xylosoxidans airway infection is associated with lung disease severity in children with cystic fibrosis.","volume":"7","author":"Marsac","year":"2021","journal-title":"ERJ. Open. Res."},{"key":"B32","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1128\/AAC.44.3.658-664.2000","article-title":"Assignment of the substrate-selective subunits of the MexEF-OprN multidrug efflux pump of Pseudomonas aeruginosa.","volume":"44","author":"Maseda","year":"2000","journal-title":"Antimicrob. Agents Chemother."},{"key":"B33","doi-asserted-by":"publisher","first-page":"4656","DOI":"10.1128\/AAC.00279-12","article-title":"Molecular epidemiology of Staphylococcus epidermidis clinical isolates from U.S. hospitals.","volume":"56","author":"Mendes","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.3389\/fmicb.2016.01223","article-title":"Berberine Is a Novel Type Efflux Inhibitor Which Attenuates the MexXY-Mediated Aminoglycoside Resistance in Pseudomonas aeruginosa.","volume":"7","author":"Morita","year":"2016","journal-title":"Front. Microbiol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1601847","DOI":"10.1183\/13993003.01847-2016","article-title":"Acquired resistance to macrolides in Pseudomonas aeruginosa from cystic fibrosis patients.","volume":"49","author":"Mustafa","year":"2017","journal-title":"Eur. Respir. J."},{"key":"B36","first-page":"1","author":"Nei","year":"2000","journal-title":"Molecular Evolution and Phylogenetics."},{"key":"B37","doi-asserted-by":"publisher","first-page":"14","DOI":"10.3390\/pathogens8010014","article-title":"Motility, Biofilm Formation and Antimicrobial Efflux of Sessile and Planktonic Cells of Achromobacter xylosoxidans.","volume":"8","author":"Nielsen","year":"2019","journal-title":"Pathogens."},{"key":"B38","doi-asserted-by":"crossref","first-page":"3016","DOI":"10.1128\/JCM.00859-12","article-title":"Rapid detection of extended-spectrum-beta-lactamase-producing Enterobacteriaceae.","volume":"50","author":"Nordmann","year":"","journal-title":"J. Clin. Microbiol."},{"key":"B39","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.3201\/eid1809.120355","article-title":"Rapid detection of carbapenemase-producing Enterobacteriaceae.","volume":"18","author":"Nordmann","year":"","journal-title":"Emerg. Infect. Dis."},{"key":"B40","doi-asserted-by":"publisher","first-page":"21964","DOI":"10.1074\/jbc.272.35.21964","article-title":"Use of fluorescence probes to monitor function of the subunit proteins of the MexA-MexB-oprM drug extrusion machinery in Pseudomonas aeruginosa.","volume":"272","author":"Ocaktan","year":"1997","journal-title":"J. Biol. Chem."},{"key":"B41","doi-asserted-by":"publisher","first-page":"e1467","DOI":"10.1128\/AAC.01467-20","article-title":"Longitudinal surveillance and combination antimicrobial susceptibility testing of multidrug-resistant Achromobacter spp. From cystic fibrosis patients.","volume":"64","author":"Okoliegbe","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"B42","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.ram.2019.03.004","article-title":"Diversity of Achromobacter species recovered from patients with cystic fibrosis, in Argentina.","volume":"52","author":"Papalia","year":"2020","journal-title":"Rev. Argent Microbiol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"7276","DOI":"10.1128\/AAC.01785-15","article-title":"Polymyxin Susceptibility in Pseudomonas aeruginosa Linked to the MexXY-OprM Multidrug Efflux System.","volume":"59","author":"Poole","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"B44","doi-asserted-by":"publisher","first-page":"700","DOI":"10.1097\/INF.0000000000000714","article-title":"Increased Prevalence and Resistance of Important Pathogens Recovered from Respiratory Specimens of Cystic Fibrosis Patients During a Decade.","volume":"34","author":"Raidt","year":"2015","journal-title":"Pediatr. Infect. Dis. J."},{"key":"B45","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1111\/j.1600-0463.2008.00995.x","article-title":"Achromobacter xylosoxidans respiratory tract infections in cystic fibrosis patients.","volume":"116","author":"Raso","year":"2008","journal-title":"APMIS"},{"key":"B46","doi-asserted-by":"publisher","first-page":"3942","DOI":"10.1128\/JCM.39.11.3942-3945.2001","article-title":"Identification and antimicrobial susceptibility of Alcaligenes xylosoxidans isolated from patients with cystic fibrosis.","volume":"39","author":"Saiman","year":"2001","journal-title":"J. Clin. Microbiol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"e29","DOI":"10.1128\/mSystems.00029-16","article-title":"Long-Term Evolution of Burkholderia multivorans during a Chronic Cystic Fibrosis Infection Reveals Shifting Forces of Selection.","volume":"1","author":"Silva","year":"2016","journal-title":"mSystems"},{"key":"B48","doi-asserted-by":"publisher","first-page":"1412","DOI":"10.1513\/AnnalsATS.201701-071OC","article-title":"Clinical Outcomes Associated with Achromobacter Species Infection in Patients with Cystic Fibrosis.","volume":"14","author":"Somayaji","year":"2017","journal-title":"Ann. Am. Thorac. Soc."},{"key":"B49","doi-asserted-by":"publisher","first-page":"3010","DOI":"10.1128\/JCM.00814-12","article-title":"A multilocus sequence typing scheme implies population structure and reveals several putative novel Achromobacter species.","volume":"50","author":"Spilker","year":"2012","journal-title":"J. Clin. Microbiol."},{"key":"B50","first-page":"2751","article-title":"Other gram-negative and gram-variable bacilli","author":"Steinberg","year":"2005","journal-title":"Principles and practices of infectious diseases, 6th ed"},{"key":"B51","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1513\/AnnalsATS.201406-288FR","article-title":"Achromobacter respiratory infections.","volume":"12","author":"Swenson","year":"2015","journal-title":"Ann. Am. Thorac. Soc."},{"key":"B52","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1128\/AAC.43.2.406","article-title":"Detection of gyrA mutations among 335 Pseudomonas aeruginosa strains isolated in Japan and their susceptibilities to fluoroquinolones.","volume":"43","author":"Takenouchi","year":"1999","journal-title":"Antimicrob. Agents Chemother."},{"key":"B53","doi-asserted-by":"publisher","first-page":"3022","DOI":"10.1093\/molbev\/msab120","article-title":"MEGA11: Molecular Evolutionary Genetics Analysis Version 11.","volume":"38","author":"Tamura","year":"2021","journal-title":"Mol. Biol. Evol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"00051","DOI":"10.1183\/23120541.00051-2019","article-title":"Impact of Achromobacter xylosoxidans isolation on the respiratory function of adult patients with cystic fibrosis.","volume":"5","author":"Tetart","year":"2019","journal-title":"ERJ. Open. Res."},{"key":"B55","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1007\/s00284-012-0213-5","article-title":"Achromobacter xylosoxidans: an emerging pathogen carrying different elements involved in horizontal genetic transfer.","volume":"65","author":"Traglia","year":"2012","journal-title":"Curr. Microbiol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1016\/j.jcf.2013.04.013","article-title":"Early treatment with inhaled antibiotics postpones next occurrence of Achromobacter in cystic fibrosis.","volume":"12","author":"Wang","year":"2013","journal-title":"J. Cyst. Fibros."},{"key":"B57","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1111\/j.1348-0421.1971.tb00607.x","article-title":"Achromobacter xylosoxidans n. sp. from human ear discharge.","volume":"15","author":"Yabuuchi","year":"1971","journal-title":"Jpn. J. Microbiol."},{"key":"B58","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1128\/AAC.34.6.1271","article-title":"Quinolone resistance-determining region in the DNA gyrase gyrA gene of Escherichia coli.","volume":"34","author":"Yoshida","year":"1990","journal-title":"Antimicrob. Agents Chemother."},{"key":"B59","doi-asserted-by":"publisher","first-page":"e2315","DOI":"10.1128\/AAC.02315-18","article-title":"Resurrecting Old beta-Lactams: Potent Inhibitory Activity of Temocillin against Multidrug-Resistant Burkholderia Species Isolates from the United States.","volume":"63","author":"Zeiser","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"B60","doi-asserted-by":"publisher","first-page":"580240","DOI":"10.1155\/2015\/580240","article-title":"Identification and characterization of a serious multidrug resistant Stenotrophomonas maltophilia strain in China.","volume":"2015","author":"Zhao","year":"2015","journal-title":"Biomed. Res. Int."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2022.762307\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T21:52:03Z","timestamp":1648590723000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2022.762307\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,28]]},"references-count":60,"alternative-id":["10.3389\/fmicb.2022.762307"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2022.762307","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,28]]},"article-number":"762307"}}