{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:38:37Z","timestamp":1790876317506,"version":"4.1.0"},"reference-count":133,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,4,30]],"date-time":"2021-04-30T00:00:00Z","timestamp":1619740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["P33617-B"],"award-info":[{"award-number":["P33617-B"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p><jats:italic>Pseudomonas aeruginosa<\/jats:italic> (<jats:italic>Pae<\/jats:italic>) is notorious for its high-level resistance toward clinically used antibiotics. In fact, <jats:italic>Pae<\/jats:italic> has rendered most antimicrobials ineffective, leaving polymyxins and aminoglycosides as last resort antibiotics. Although several resistance mechanisms of <jats:italic>Pae<\/jats:italic> are known toward these drugs, a profounder knowledge of hitherto unidentified factors and pathways appears crucial to develop novel strategies to increase their efficacy. Here, we have performed for the first time transcriptome analyses and ribosome profiling in parallel with strain PA14 grown in synthetic cystic fibrosis medium upon exposure to polymyxin E (colistin) and tobramycin. This approach did not only confirm known mechanisms involved in colistin and tobramycin susceptibility but revealed also as yet unknown functions\/pathways. Colistin treatment resulted primarily in an anti-oxidative stress response and in the de-regulation of the MexT and AlgU regulons, whereas exposure to tobramycin led predominantly to a rewiring of the expression of multiple amino acid catabolic genes, lower tricarboxylic acid (TCA) cycle genes, type II and VI secretion system genes and genes involved in bacterial motility and attachment, which could potentially lead to a decrease in drug uptake. Moreover, we report that the adverse effects of tobramycin on translation are countered with enhanced expression of genes involved in stalled ribosome rescue, tRNA methylation and type II toxin-antitoxin (TA) systems.<\/jats:p>","DOI":"10.3389\/fmicb.2021.626715","type":"journal-article","created":{"date-parts":[[2021,4,30]],"date-time":"2021-04-30T08:27:11Z","timestamp":1619771231000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":34,"title":["Gene Expression Profiling of Pseudomonas aeruginosa Upon Exposure to Colistin and Tobramycin"],"prefix":"10.3389","volume":"12","author":[{"given":"Anastasia","family":"Cianciulli Sesso","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Branislav","family":"Lili\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"Amman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael T.","family":"Wolfinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Sonnleitner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Udo","family":"Bl\u00e4si","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,4,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1046\/j.1365-2443.2002.00549.x","article-title":"SsrA-mediated protein tagging in the presence of miscoding drugs and its physiological role in Escherichia coli.","volume":"7","author":"Aboa","year":"2002","journal-title":"Genes Cells"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2010-11-10-r106","article-title":"Differential expression analysis for sequence count data.","volume":"11","author":"Anders","year":"2010","journal-title":"Genome Biol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"175","DOI":"10.2147\/IDR.S49039","article-title":"Pseudomonas aeruginosa induces pigment production and enhances virulence in a white phenotypic variant of Staphylococcus aureus.","volume":"6","author":"Antonic","year":"2013","journal-title":"Infect. Drug Resist."},{"key":"B4","doi-asserted-by":"publisher","first-page":"5150","DOI":"10.1128\/AAC.00893-09","article-title":"Alterations in two-component regulatory systems of phoPQ and pmrAB are associated with polymyxin B resistance in clinical isolates of Pseudomonas aeruginosa.","volume":"53","author":"Barrow","year":"2009","journal-title":"Antimicrob. Agents Chemother."},{"key":"B5","doi-asserted-by":"publisher","first-page":"e02040","DOI":"10.1128\/AAC.02040-19","article-title":"Adaptive and mutational responses to peptide dendrimer antimicrobials in Pseudomonas aeruginosa.","volume":"64","author":"Ben Jeddou","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1101\/501478","article-title":"Using ribosome profiling to quantify differences in protein expression: a case study in Saccharomyces cerevisiae oxidative stress conditions.","volume":"501478","author":"Blevins","year":"2018","journal-title":"bioRxiv"},{"key":"B7","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1016\/j.tim.2011.04.005","article-title":"Pseudomonas aeruginosa: all roads lead to resistance.","volume":"19","author":"Breidenstein","year":"2011","journal-title":"Trends Microbiol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1016\/j.ijantimicag.2013.10.015","article-title":"Bactericidal effect of colistin on planktonic Pseudomonas aeruginosa is independent of hydroxyl radical formation.","volume":"43","author":"Brochmann","year":"2014","journal-title":"Int. J. Antimicrob. Agents"},{"key":"B9","doi-asserted-by":"publisher","first-page":"6536","DOI":"10.1128\/jb.177.22.6536-6544.1995","article-title":"Cloning and characterization of the katB gene of Pseudomonas aeruginosa encoding a hydrogen peroxide-inducible catalase: purification of KatB, cellular localization, and demonstration that it is essential for optimal resistance to hydrogen p.","volume":"177","author":"Brown","year":"1995","journal-title":"J. Bacteriol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1007\/s10534-006-0003-2","article-title":"Feo - Transport of ferrous iron into bacteria.","volume":"19","author":"Cartron","year":"2006","journal-title":"BioMetals"},{"key":"B11","doi-asserted-by":"publisher","first-page":"321","DOI":"10.3390\/ijms16010321","article-title":"tRNAs as antibiotic targets.","volume":"16","author":"Chopra","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"B12","doi-asserted-by":"publisher","first-page":"2826","DOI":"10.1099\/mic.0.025643-0","article-title":"Subinhibitory concentrations of the cationic antimicrobial peptide colistin induce the pseudomonas quinolone signal in Pseudomonas aeruginosa.","volume":"155","author":"Cummins","year":"2009","journal-title":"Microbiology"},{"key":"B13","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1111\/j.1365-2958.2012.08049.x","article-title":"Proteolytic regulation of alginate overproduction in Pseudomonas aeruginosa.","volume":"84","author":"Damron","year":"2012","journal-title":"Mol. Microbiol."},{"key":"B14","first-page":"1708","article-title":"Increased sensitivity to protein synthesis inhibitors in cells lacking tmRNA.","volume":"7","author":"de la Cruz","year":"2001","journal-title":"RNA"},{"key":"B15","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1038\/ja.2013.111","article-title":"A secondary mode of action of polymyxins against Gram-negative bacteria involves the inhibition of NADH-quinone oxidoreductase activity.","volume":"67","author":"Deris","year":"2014","journal-title":"J. Antibiot."},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.2013.1055","article-title":"Switching between apparently redundant iron-uptake mechanisms benefits bacteria in changeable environments.","volume":"280","author":"Dumas","year":"2013","journal-title":"Proc. R. Soc. B Biol. Sci."},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2020.1754133","article-title":"Colistin and its Role in the Era of Antibiotic Resistance: an extended review (2000-2019).","volume":"9","author":"El-Sayed Ahmed","year":"2020","journal-title":"Emerg. Microbes Infect."},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0001619","article-title":"The Neglected Intrinsic Resistome of Bacterial Pathogens.","volume":"3","author":"Fajardo","year":"2008","journal-title":"PLoS One"},{"key":"B19","doi-asserted-by":"publisher","first-page":"3502","DOI":"10.1128\/JB.06632-11","article-title":"MexT Functions as a Redox-Responsive Regulator Modulating Disulfide Stress Resistance in Pseudomonas aeruginosa.","volume":"194","author":"Fargier","year":"2012","journal-title":"J. Bacteriol."},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1101\/2020.01.09.900639","article-title":"Response of Pseudomonas aeruginosa to the innate immune system-derived oxidants hypochlorous acid and hypothiocyanous acid.","author":"Farrant","year":"2020","journal-title":"bioRxiv."},{"key":"B21","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1128\/AAC.01583-12","article-title":"Characterization of the polymyxin B resistome of Pseudomonas aeruginosa.","volume":"57","author":"Fern\u00e1ndez","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"B22","doi-asserted-by":"publisher","first-page":"3372","DOI":"10.1128\/AAC.00242-10","article-title":"Adaptive resistance to the \u201clast hope\u201d antibiotics polymyxin B and colistin in Pseudomonas aeruginosa is mediated by the novel two-component regulatory system ParR-ParS.","volume":"54","author":"Fern\u00e1ndez","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"B23","doi-asserted-by":"publisher","first-page":"6212","DOI":"10.1128\/AAC.01530-12","article-title":"The two-component system CprRS senses cationic peptides and triggers adaptive resistance in Pseudomonas aeruginosa independently of ParRS.","volume":"56","author":"Fern\u00e1ndez","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"B24","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1128\/AAC.00830-10","article-title":"mexEF-oprN multidrug efflux operon of Pseudomonas aeruginosa: regulation by the MexT activator in response to nitrosative stress and chloramphenicol.","volume":"55","author":"Fetar","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"B25","doi-asserted-by":"publisher","first-page":"4478","DOI":"10.1128\/AAC.01072-08","article-title":"MexCD-OprJ multidrug efflux system of Pseudomonas aeruginosa: involvement in chlorhexidine resistance and induction by membrane-damaging agents dependent upon the AlgU stress response sigma factor.","volume":"52","author":"Fraud","year":"2008","journal-title":"Antimicrob. Agents Chemother."},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms8226","article-title":"Maintenance of protein synthesis reading frame by EF-P and m 1 G37-tRNA.","volume":"6","author":"Gamper","year":"2015","journal-title":"Nat. Commun."},{"key":"B27","doi-asserted-by":"publisher","first-page":"14866","DOI":"10.3390\/ijms160714866","article-title":"The UGG Isoacceptor of tRNAPro Is Naturally Prone to Frameshifts.","volume":"16","author":"Gamper","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"B28","doi-asserted-by":"publisher","first-page":"2742","DOI":"10.1097\/01.CCM.0000098031.24329.10","article-title":"Impact of adequate empirical antibiotic therapy on the outcome of patients admitted to the intensive care unit with sepsis.","volume":"31","author":"Garnacho-Montero","year":"2003","journal-title":"Crit. Care Med."},{"key":"B29","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1039\/c5md00344j","article-title":"Mechanisms of resistance to aminoglycoside antibiotics: overview and perspectives.","volume":"7","author":"Garneau-Tsodikova","year":"2016","journal-title":"Medchemcomm"},{"key":"B30","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1111\/2049-632X.12033","article-title":"Pseudomonas aeruginosa: new insights into pathogenesis and host defenses.","volume":"67","author":"Gellatly","year":"2013","journal-title":"Pathog. Dis."},{"key":"B31","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/j.febslet.2004.04.086","article-title":"BOF: a novel family of bacterial OB-fold proteins.","volume":"567","author":"Ginalski","year":"2004","journal-title":"FEBS Lett."},{"key":"B32","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1128\/JB.00963-15","article-title":"The Pseudomonas aeruginosa PAO1 two-component regulator CarSR regulates calcium homeostasis and calcium induced virulence factor production through its regulatory targets CarO and CarP.","volume":"198","author":"Guragain","year":"2016","journal-title":"J. Bacteriol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"2204","DOI":"10.1128\/AAC.02353-12","article-title":"Polymyxin resistance of Pseudomonas aeruginosa phoQ mutants is dependent on additional two-component regulatory systems.","volume":"57","author":"Gutu","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"B34","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.sbi.2004.01.010","article-title":"Dial tm for rescue: tmRNA engages ribosomes stalled on defective mRNAs.","volume":"14","author":"Haebel","year":"2004","journal-title":"Curr. Opin. Struct. Biol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"e00149","DOI":"10.1128\/msystems.00149-18","article-title":"Comparative Metabolomics and Transcriptomics Reveal Multiple Pathways Associated with Polymyxin Killing in Pseudomonas aeruginosa.","volume":"4","author":"Han","year":"2019","journal-title":"mSystems"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1391","DOI":"10.1242\/jcs.00365","article-title":"Antibiotics acting on the translational machinery.","volume":"116","author":"Harms","year":"2003","journal-title":"J. Cell Sci."},{"key":"B37","doi-asserted-by":"publisher","first-page":"6330","DOI":"10.1128\/jb.177.22.6330-6337.1995","article-title":"Pseudomonas aeruginosa sodA and sodB mutants defective in manganese- and iron-cofactored superoxide dismutase activity demonstrate the importance of the iron-cofactored form in aerobic metabolism.","volume":"177","author":"Hassett","year":"1995","journal-title":"J. Bacteriol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"7658","DOI":"10.1128\/jb.175.23.7658-7665.1993","article-title":"Cloning and characterization of the Pseudomonas aeruginosa sodA and sodB genes encoding manganese- and iron-cofactored superoxide dismutase: demonstration of increased manganese superoxide dismutase activity in alginate-producing bact.","volume":"175","author":"Hassett","year":"1993","journal-title":"J. Bacteriol."},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0056858","article-title":"Antibiotic Inducibility of the mexXY Multidrug Efflux Operon of Pseudomonas aeruginosa: involvement of the MexZ Anti-Repressor ArmZ.","volume":"8","author":"Hay","year":"2013","journal-title":"PLoS One"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0101033","article-title":"Impact of Acinetobacter baumannii superoxide dismutase on motility, virulence, oxidative stress resistance and susceptibility to antibiotics.","volume":"9","author":"Heindorf","year":"2014","journal-title":"PLoS One"},{"key":"B41","doi-asserted-by":"publisher","first-page":"e00232","DOI":"10.1128\/JB.00232-19","article-title":"Loss of RNA chaperone Hfq unveils a toxic pathway in Pseudomonas aeruginosa.","volume":"201","author":"Hill","year":"2019","journal-title":"J. Bacteriol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"4790","DOI":"10.1128\/JB.05133-11","article-title":"Membrane proteases and aminoglycoside antibiotic resistance.","volume":"193","author":"Hinz","year":"2011","journal-title":"J. Bacteriol."},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1000502","article-title":"Fast mapping of short sequences with mismatches, insertions and deletions using index structures.","volume":"5","author":"Hoffmann","year":"2009","journal-title":"PLoS Comput. Biol."},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-10778-w","article-title":"An integrated genomic regulatory network of virulence-related transcriptional factors in Pseudomonas aeruginosa.","volume":"10","author":"Huang","year":"2019","journal-title":"Nat. Commun."},{"key":"B45","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1126\/science.1168978","article-title":"Genome-wide analysis in vivo of translation with nucleotide resolution using ribosome profiling.","volume":"324","author":"Ingolia","year":"2009","journal-title":"Science"},{"key":"B46","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1016\/j.ijantimicag.2017.02.026","article-title":"Correlation between phenotypic antibiotic susceptibility and the resistome in Pseudomonas aeruginosa.","volume":"50","author":"Jaillard","year":"2017","journal-title":"Int. J. Antimicrob. Agents"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2018.04.3716","article-title":"Emergence of Colistin Resistance among Gram Negative Bacteria in Urinary Tract Infections from Super Specialty Hospital of North India.","volume":"73","author":"Jain","year":"2018","journal-title":"Int. J. Infect. Dis."},{"key":"B48","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1016\/j.ijantimicag.2016.11.029","article-title":"Resistance to polymyxins in Gram-negative organisms.","volume":"49","author":"Jeannot","year":"2017","journal-title":"Int. J. Antimicrob. Agents"},{"key":"B49","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1128\/JB.05230-11","article-title":"Surface-localized spermidine protects the Pseudomonas aeruginosa: outer membrane from antibiotic treatment and oxidative stress.","volume":"194","author":"Johnson","year":"2011","journal-title":"J. Bacteriol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1016\/j.jhin.2009.04.020","article-title":"Pseudomonas aeruginosa: a formidable and ever-present adversary.","volume":"73","author":"Kerr","year":"2009","journal-title":"J. Hosp. Infect."},{"key":"B51","doi-asserted-by":"publisher","first-page":"1272","DOI":"10.1016\/j.bbamcr.2014.12.010","article-title":"Iron-sulfur proteins responsible for RNA modifications.","volume":"1853","author":"Kimura","year":"2015","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"B52","doi-asserted-by":"publisher","first-page":"1874","DOI":"10.1128\/AAC.00935-10","article-title":"Involvement of an ATP-dependent protease, PA0779\/AsrA, in inducing heat shock in response to tobramycin in Pseudomonas aeruginosa.","volume":"55","author":"Kindrachuk","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"B53","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/j.cell.2007.06.049","article-title":"A common mechanism of cellular death induced by bactericidal antibiotics.","volume":"130","author":"Kohanski","year":"2007","journal-title":"Cell"},{"key":"B54","doi-asserted-by":"publisher","first-page":"6300","DOI":"10.1128\/jb.181.20.6300-6305.1999","article-title":"Characterization of MexT, the regulator of the MexE-MexF-OprN multidrug efflux system of Pseudomonas aeruginosa.","volume":"181","author":"K\u00f6hler","year":"1999","journal-title":"J. Bacteriol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1046\/j.1365-2958.1997.2281594.x","article-title":"Characterization of MexE-MexF-OprN, a positively regulated multidrug efflux system of Pseudomonas aeruginosa.","volume":"23","author":"K\u00f6hler","year":"","journal-title":"Mol. Microbiol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"2540","DOI":"10.1128\/aac.41.11.2540","article-title":"Differential selection of multidrug efflux systems by quinolones in Pseudomonas aeruginosa.","volume":"41","author":"K\u00f6hler","year":"","journal-title":"Antimicrob. Agents Chemother."},{"key":"B57","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1007\/s00604-011-0547-x","article-title":"Interaction of polymyxin B with ds-DNA, and determination of DNA or polymyxin B via resonance Rayleigh scattering and resonance non-linear scattering spectra.","volume":"173","author":"Kong","year":"2011","journal-title":"Microchim. Acta"},{"key":"B58","doi-asserted-by":"publisher","first-page":"5242","DOI":"10.1128\/JB.187.15.5242-5248.2005","article-title":"Characterization of a multigene-encoded sodium\/hydrogen antiporter (Sha) from Pseudomonas aeruginosa: its involvement in pathogenesis.","volume":"187","author":"Kosono","year":"2005","journal-title":"J. Bacteriol."},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a027029","article-title":"Aminoglycosides: an overview.","volume":"6","author":"Krause","year":"2016","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02549-14","article-title":"The ferrous iron-responsive BqsRS two-component system activates genes that promote cationic stress tolerance.","volume":"6","author":"Kreamer","year":"2015","journal-title":"MBio"},{"key":"B61","doi-asserted-by":"publisher","first-page":"1195","DOI":"10.1128\/JB.05634-11","article-title":"BqsR\/BqsS Constitute a Two-Component System That Senses Extracellular Fe(II) in Pseudomonas aeruginosa.","volume":"194","author":"Kreamer","year":"2012","journal-title":"J Bacteriol."},{"key":"B62","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1099\/mic.0.26085-0","article-title":"Identification and characterization of novel pyoverdine synthesis genes in Pseudomonas aeruginosa.","volume":"149","author":"Lamont","year":"2003","journal-title":"Microbiology"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1186\/s12866-019-1485-8","article-title":"Evaluation of the interaction between polymyxin B and Pseudomonas aeruginosa biofilm and planktonic cells: reactive oxygen species induction and zeta potential.","volume":"19","author":"Lima","year":"2019","journal-title":"BMC Microbiol"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002854","article-title":"A novel virulence strategy for Pseudomonas aeruginosa mediated by an autotransporter with arginine-specific aminopeptidase activity.","volume":"8","author":"Luckett","year":"2012","journal-title":"PLoS Pathog."},{"key":"B65","doi-asserted-by":"publisher","first-page":"3730","DOI":"10.1128\/jb.181.12.3730-3742.1999","article-title":"Bacterioferritin A modulates catalase A (KatA) activity and resistance to hydrogen peroxide in Pseudomonas aeruginosa.","volume":"181","author":"Ma","year":"1999","journal-title":"J. Bacteriol."},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.14806\/ej.17.1.200","article-title":"Cutadapt removes adapter sequences from high-throughput sequencing reads.","volume":"17","author":"Martin","year":"2011","journal-title":"EMBnet J."},{"key":"B67","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1016\/j.cels.2019.03.008","article-title":"tRNA Methylation Is a Global Determinant of Bacterial Multi-drug Resistance.","volume":"8","author":"Masuda","year":"2019","journal-title":"Cell Syst."},{"key":"B68","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/S0014-5793(03)00767-1","article-title":"The \u201cantiporter module\u201d of respiratory chain Complex I includes the MrpC\/NuoK subunit - A revision of the modular evolution scheme.","volume":"549","author":"Mathiesen","year":"2003","journal-title":"FEBS Lett."},{"key":"B69","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1046\/j.1365-2958.2003.03673.x","article-title":"Cationic antimicrobial peptides activate a two-component regulatory system, PmrA-PmrB, that regulates resistance to polymyxin B and cationic antimicrobial peptides in Pseudomonas aeruginosa.","volume":"50","author":"McPhee","year":"2003","journal-title":"Mol. Microbiol."},{"key":"B70","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1099\/00221287-107-2-319","article-title":"The Fluorescent Pigment of Pseudomonas fluorescens: biosynthesis, Purification and Physicochemical Properties.","volume":"107","author":"Meyer","year":"1978","journal-title":"J. Gen. Microbiol."},{"key":"B71","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.chembiol.2016.12.015","article-title":"Carbon Sources Tune Antibiotic Susceptibility in Pseudomonas aeruginosa via Tricarboxylic Acid Cycle Control.","volume":"24","author":"Meylan","year":"2017","journal-title":"Cell Chem. Biol."},{"key":"B72","doi-asserted-by":"publisher","first-page":"28","DOI":"10.5507\/bp.2018.070","article-title":"Molecular mechanisms of polymyxin resistance and detection of mcr genes.","volume":"163","author":"Mlynarcik","year":"2019","journal-title":"Biomed. Pap."},{"key":"B73","doi-asserted-by":"publisher","first-page":"1847","DOI":"10.1128\/JB.188.5.1847-1855.2006","article-title":"Antibiotic inducibility of the MexXY multidrug efflux system of Pseudomonas aeruginosa: involvement of the antibiotic-inducible PA5471 gene product.","volume":"188","author":"Morita","year":"2006","journal-title":"J. Bacteriol."},{"key":"B74","doi-asserted-by":"publisher","first-page":"3012","DOI":"10.1128\/IAI.74.5.3012-3015.2006","article-title":"The posttranscriptional regulator RsmA plays a role in the interaction between Pseudomonas aeruginosa and human airway epithelial cells by positively regulating the type III secretion system.","volume":"74","author":"Mulcahy","year":"2006","journal-title":"Infect. Immun."},{"key":"B75","doi-asserted-by":"publisher","first-page":"1211","DOI":"10.1128\/AAC.01252-10","article-title":"A two-component regulatory system interconnects resistance to polymyxins, aminoglycosides, fluoroquinolones, and \u03b2-lactams in Pseudomonas aeruginosa.","volume":"55","author":"Muller","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"B76","doi-asserted-by":"publisher","first-page":"e01603","DOI":"10.1128\/mBio.01603-15","article-title":"Intrinsic antimicrobial resistance determinants in the superbug pseudomonas aeruginosa.","volume":"6","author":"Murray","year":"2015","journal-title":"MBio"},{"key":"B77","doi-asserted-by":"publisher","first-page":"6766","DOI":"10.1128\/JB.01318-12","article-title":"New substrates on the block: clinically relevant resistances for EmrE and homologues.","volume":"194","author":"Nasie","year":"2012","journal-title":"J. Bacteriol."},{"key":"B78","doi-asserted-by":"publisher","first-page":"4606","DOI":"10.1128\/AAC.48.12.4606-4610.2004","article-title":"National surveillance of antimicrobial resistance in Pseudomonas aeruginosa isolates obtained from intensive care unit patients from 1993 to 2002.","volume":"48","author":"Obritsch","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"B79","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1099\/00221287-146-1-185","article-title":"Genetics and regulation of two distinct haem-uptake systems, phu and has, in Pseudomonas aeruginosa.","volume":"146","author":"Ochsner","year":"","journal-title":"Microbiology"},{"key":"B80","doi-asserted-by":"publisher","first-page":"4533","DOI":"10.1128\/JB.182.16.4533-4544.2000","article-title":"Role of the Pseudomonas aeruginosa oxyR-recG operon in oxidative stress defense and DNA repair: oxyR-dependent regulation of katB-ankB, ahpB, and ahpC-ahpF.","volume":"182","author":"Ochsner","year":"","journal-title":"J. Bacteriol."},{"key":"B81","doi-asserted-by":"publisher","first-page":"4409","DOI":"10.1073\/pnas.93.9.4409","article-title":"Gene repression by the ferric uptake regulator in Pseudomonas aeruginosa: cycle selection of iron-regulated genes.","volume":"93","author":"Ochsner","year":"1996","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B82","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1007\/s00203-018-1485-3","article-title":"Colistin causes profound morphological alteration but minimal cytoplasmic membrane perforation in populations of Escherichia coli and Pseudomonas aeruginosa.","volume":"200","author":"O\u2019Driscoll","year":"2018","journal-title":"Arch. Microbiol."},{"key":"B83","doi-asserted-by":"publisher","first-page":"1968","DOI":"10.1111\/j.1462-2920.2012.02727.x","article-title":"Overproduction of the multidrug efflux pump MexEF-OprN does not impair Pseudomonas aeruginosa fitness in competition tests, but produces specific changes in bacterial regulatory networks.","volume":"14","author":"Olivares","year":"2012","journal-title":"Environ. Microbiol."},{"key":"B84","doi-asserted-by":"publisher","first-page":"2958","DOI":"10.1128\/IAI.73.5.2958-2966.2005","article-title":"Pseudomonas aeruginosa SoxR does not conform to the archetypal paradigm for SoxR-dependent regulation of the bacterial oxidative stress adaptive response.","volume":"73","author":"Palma","year":"2005","journal-title":"Infect. Immun."},{"key":"B85","doi-asserted-by":"publisher","first-page":"8079","DOI":"10.1128\/JB.01138-07","article-title":"Nutritional cues control Pseudomonas aeruginosa multicellular behavior in cystic fibrosis sputum.","volume":"189","author":"Palmer","year":"2007","journal-title":"J. Bacteriol."},{"key":"B86","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1111\/j.1365-2958.2008.06152.x","article-title":"Tolerance to the antimicrobial peptide colistin in Pseudomonas aeruginosa biofilms is linked to metabolically active cells, and depends on the pmr and mexAB-oprM genes.","volume":"68","author":"Pamp","year":"2008","journal-title":"Mol. Microbiol."},{"key":"B87","doi-asserted-by":"publisher","first-page":"7243","DOI":"10.1128\/JB.00688-09","article-title":"A protein important for antimicrobial peptide resistance, YdeI\/OmdA, is in the periplasm and interacts with OmpD\/NmpC.","volume":"191","author":"Pilonieta","year":"2009","journal-title":"J. Bacteriol."},{"key":"B88","doi-asserted-by":"publisher","first-page":"2217","DOI":"10.1128\/JB.00234-15","article-title":"The Pseudomonas aeruginosa PA14 ABC transporter NppA1A2BCD is required for uptake of peptidyl nucleoside antibiotics.","volume":"197","author":"Pletzer","year":"2015","journal-title":"J. Bacteriol."},{"key":"B89","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1128\/CMR.00064-16","article-title":"Polymyxins: antibacterial activity, susceptibility testing, and resistance mechanisms encoded by plasmids or chromosomes.","volume":"30","author":"Poirel","year":"2017","journal-title":"Clin. Microbiol. Rev."},{"key":"B90","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1128\/AAC.49.2.479-487.2005","article-title":"Aminoglycoside resistance in Pseudomonas aeruginosa.","volume":"49","author":"Poole","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"B91","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":"B92","doi-asserted-by":"publisher","first-page":"828","DOI":"10.1128\/AAC.01439-13","article-title":"Growth retardation, reduced invasiveness, and impaired colistin-mediated cell death associated with colistin resistance development in Acinetobacter baumannii.","volume":"58","author":"Pournaras","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"B93","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1093\/bioinformatics\/btq033","article-title":"BEDTools: a flexible suite of utilities for comparing genomic features.","volume":"26","author":"Quinlan","year":"2010","journal-title":"Bioinformatics"},{"key":"B94","doi-asserted-by":"publisher","first-page":"1899","DOI":"10.1126\/science.7604262","article-title":"Common virulence factors for bacterial pathogenicity in plants and animals.","volume":"268","author":"Rahme","year":"1995","journal-title":"Science"},{"key":"B95","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1056\/NEJM199901073400104","article-title":"Intermittent administration of inhaled tobramycin in patients with cystic fibrosis.","volume":"340","author":"Ramsey","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"B96","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1146\/annurev.micro.54.1.881","article-title":"Iron Metabolism in Pathogenic Bacteria.","volume":"54","author":"Ratledge","year":"2000","journal-title":"Annu. Rev. Microbiol."},{"key":"B97","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1016\/j.bbabio.2013.05.001","article-title":"Reprint of: iron\/sulfur proteins biogenesis in prokaryotes: formation, regulation and diversity.","volume":"1827","author":"Roche","year":"2013","journal-title":"Biochim. Biophys. Acta Bioenerg."},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0086763","article-title":"The iron-sulphur cluster biosynthesis regulator IscR contributes to iron homeostasis and resistance to oxidants in Pseudomonas aeruginosa.","volume":"9","author":"Romsang","year":"2014","journal-title":"PLoS One"},{"key":"B99","doi-asserted-by":"publisher","first-page":"2565","DOI":"10.1128\/JB.187.8.2565","article-title":"Genome-Wide Transcriptional Profiling of the Steady-State Response of Pseudomonas aeruginosa to Hydrogen Peroxide.","volume":"187","author":"Salunkhe","year":"2005","journal-title":"Society"},{"key":"B100","doi-asserted-by":"publisher","first-page":"5642","DOI":"10.1128\/AAC.00756-12","article-title":"Rapid killing of Acinetobacter baumannii by polymyxins is mediated by a hydroxyl radical death pathway.","volume":"56","author":"Sampson","year":"2012","journal-title":"Antimicrob Agents Chemother"},{"key":"B101","doi-asserted-by":"publisher","first-page":"4310","DOI":"10.1128\/JB.00240-07","article-title":"The anaerobic regulatory network required for Pseudomonas aeruginosa nitrate respiration.","volume":"189","author":"Schreiber","year":"2007","journal-title":"J. Bacteriol."},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004744","article-title":"Elucidation of Sigma Factor-Associated Networks in Pseudomonas aeruginosa Reveals a Modular Architecture with Limited and Function-Specific Crosstalk.","volume":"11","author":"Schulz","year":"2015","journal-title":"PLoS Pathog."},{"key":"B103","doi-asserted-by":"publisher","first-page":"4213","DOI":"10.1128\/AAC.00507-08","article-title":"Novel genetic determinants of low-level aminoglycoside resistance in Pseudomonas aeruginosa.","volume":"52","author":"Schurek","year":"2008","journal-title":"Antimicrob. Agents Chemother."},{"key":"B104","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1080\/14787210.2018.1453807","article-title":"Emerging Gram negative resistance to last-line antimicrobial agents fosfomycin, colistin and ceftazidime-avibactam\u2013epidemiology, laboratory detection and treatment implications.","volume":"16","author":"Sherry","year":"2018","journal-title":"Expert Rev. Anti. Infect. Ther."},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006124","article-title":"A Chemical-Genomic Screen of Neglected Antibiotics Reveals Illicit Transport of Kasugamycin and Blasticidin S.","volume":"12","author":"Shiver","year":"2016","journal-title":"PLoS Genet."},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0147811","article-title":"RNASeq Based Transcriptional Profiling of Pseudomonas aeruginosa PA14 after Short- and Long-Term Anoxic Cultivation in Synthetic Cystic Fibrosis Sputum Medium.","volume":"11","author":"Tata","year":"2016","journal-title":"PLoS One"},{"key":"B107","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/S0022-2836(02)00784-2","article-title":"The protein synthesis inhibitors, oxazolidinones and chloramphenicol, cause extensive translational inaccuracy in vivo.","volume":"322","author":"Thompson","year":"2002","journal-title":"J. Mol. Biol."},{"key":"B108","doi-asserted-by":"publisher","first-page":"7546","DOI":"10.1093\/nar\/gkp828","article-title":"Transcriptome profiling defines a novel regulon modulated by the LysR-type transcriptional regulator MexT in Pseudomonas aeruginosa.","volume":"37","author":"Tian","year":"","journal-title":"Nucleic Acids Res."},{"key":"B109","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1016\/j.micpath.2009.08.003","article-title":"MexT modulates virulence determinants in Pseudomonas aeruginosa independent of the MexEF-OprN efflux pump.","volume":"47","author":"Tian","year":"","journal-title":"Microb. Pathog."},{"key":"B110","doi-asserted-by":"publisher","first-page":"6743","DOI":"10.1128\/JB.00889-07","article-title":"Transcriptomic analysis of the sulfate starvation response of Pseudomonas aeruginosa.","volume":"189","author":"Tralau","year":"2007","journal-title":"J. Bacteriol."},{"key":"B111","doi-asserted-by":"publisher","first-page":"5387","DOI":"10.1128\/JB.187.15.5387-5396.2005","article-title":"Cationic antimicrobial peptide resistance in Neisseria meningitidis.","volume":"187","author":"Tzeng","year":"2005","journal-title":"J. Bacteriol."},{"key":"B112","author":"Valderrama-Carmona","year":"2019","journal-title":"The Role of Pseudomonas aeruginosa RNA Methyltransferases in Antibiotic Resistance,\u201d in Pseudomonas Aeruginosa - An Armory Within."},{"key":"B113","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1046\/j.1365-2958.1999.01586.x","article-title":"The response of Pseudomonas aeruginosa to iron: genetics, biochemistry and virulence.","volume":"34","author":"Vasil","year":"1999","journal-title":"Mol. Microbiol."},{"key":"B114","doi-asserted-by":"publisher","first-page":"711","DOI":"10.2217\/fmb.13.39","article-title":"Pharmacology of polymyxins: new insights into an \u2019old class of antibiotics.","volume":"8","author":"Velkov","year":"2013","journal-title":"Future Microbiol."},{"key":"B115","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.molcel.2015.05.011","article-title":"Obg and Membrane Depolarization Are Part of a Microbial Bet-Hedging Strategy that Leads to Antibiotic Tolerance.","volume":"59","author":"Verstraeten","year":"2015","journal-title":"Mol. Cell"},{"key":"B116","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1111\/j.1574-6968.2003.tb11491.x","article-title":"Trans -translation and protein synthesis inhibitors.","volume":"218","author":"Vioque","year":"2003","journal-title":"FEMS Microbiol. Lett."},{"key":"B117","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1146\/annurev.micro.58.030603.123811","article-title":"Bacterial Iron Sources: from Siderophores to Hemophores.","volume":"58","author":"Wandersman","year":"2004","journal-title":"Annu. Rev. Microbiol."},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-14-618","article-title":"Transcriptome profiling reveals links between ParS\/ParR, MexEF-OprN, and quorum sensing in the regulation of adaptation and virulence in Pseudomonas aeruginosa.","volume":"14","author":"Wang","year":"2013","journal-title":"BMC Genomics"},{"key":"B119","doi-asserted-by":"publisher","first-page":"4320","DOI":"10.1093\/nar\/gks017","article-title":"Global regulation of gene expression by OxyR in an important human opportunistic pathogen.","volume":"40","author":"Wei","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"B120","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1016\/j.ijantimicag.2017.01.023","article-title":"Emergence of colistin resistance in Pseudomonas aeruginosa ST235 clone in South Korea.","volume":"49","author":"Wi","year":"2017","journal-title":"Int. J. Antimicrob. Agents"},{"key":"B121","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.1111\/j.1440-1843.2010.01819.x","article-title":"Pseudomonas aeruginosa: host defence in lung diseases.","volume":"15","author":"Williams","year":"2010","journal-title":"Respirology"},{"key":"B122","doi-asserted-by":"publisher","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":"B123","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1146\/annurev.micro.57.030502.090945","article-title":"A Salvage Pathway for Protein Synthesis: tmRNA and Trans -Translation.","volume":"57","author":"Withey","year":"2003","journal-title":"Annu. Rev. Microbiol."},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.6157.2","article-title":"ViennaNGS: a toolbox for building efficient next-generation sequencing analysis pipelines.","volume":"4","author":"Wolfinger","year":"2015","journal-title":"F1000Res."},{"key":"B125","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1111\/j.1365-2958.2006.05390.x","article-title":"Cell wall-inhibitory antibiotics activate the alginate biosynthesis operon in Pseudomonas aeruginosa: roles of \u03c322 (AlgT) and the AlgW and Prc proteases.","volume":"62","author":"Wood","year":"2006","journal-title":"Mol. Microbiol."},{"key":"B126","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1038\/nrmicro1614","article-title":"The antibiotic resistome: the nexus of chemical and genetic diversity.","volume":"5","author":"Wright","year":"2007","journal-title":"Nat. Rev. Microbiol."},{"key":"B127","doi-asserted-by":"publisher","first-page":"2126","DOI":"10.1074\/mcp.M115.050161","article-title":"Dynamic proteome response of Pseudomonas aeruginosa to tobramycin antibiotic treatment.","volume":"14","author":"Wu","year":"2015","journal-title":"Mol. Cell. Proteomics"},{"key":"B128","doi-asserted-by":"publisher","first-page":"22689","DOI":"10.1074\/jbc.M110.127456","article-title":"Iron homeostasis affects antibiotic-mediated cell death in Pseudomonas species.","volume":"285","author":"Yeom","year":"2010","journal-title":"J. Biol. Chem."},{"key":"B129","doi-asserted-by":"publisher","first-page":"2566","DOI":"10.1128\/AAC.36.11.2566","article-title":"Role of Pseudomonas aeruginosa outer membrane protein OprH in polymyxin and gentamicin resistance: isolation of an OprH-deficient mutant by gene replacement techniques.","volume":"36","author":"Young","year":"1992","journal-title":"Antimicrob. Agents Chemother."},{"key":"B130","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24030387","article-title":"Enhanced NADH metabolism involves colistin-induced killing of Bacillus subtilis and Paenibacillus polymyxa.","volume":"24","author":"Yu","year":"2019","journal-title":"Molecules"},{"key":"B131","first-page":"1","article-title":"Oxidative stress induced by polymyxin E is involved in rapid killing of Paenibacillus polymyxa.","volume":"2017","author":"Yu","year":"2017","journal-title":"Biomed Res. Int."},{"key":"B132","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1111\/mmi.13857","article-title":"Probing the sRNA regulatory landscape of P. aeruginosa: post-transcriptional control of determinants of pathogenicity and antibiotic susceptibility.","volume":"106","author":"Zhang","year":"2017","journal-title":"Mol. Microbiol."},{"key":"B133","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1111\/j.1574-6968.2000.tb09002.x","article-title":"A second tonB gene in Pseudomonas aeruginosa is linked to the exbB and exbD genes.","volume":"184","author":"Zhao","year":"2000","journal-title":"FEMS Microbiol. Lett."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2021.626715\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,30]],"date-time":"2021-04-30T08:27:24Z","timestamp":1619771244000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2021.626715\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,30]]},"references-count":133,"alternative-id":["10.3389\/fmicb.2021.626715"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2021.626715","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,30]]},"article-number":"626715"}}