{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T02:31:51Z","timestamp":1783132311566,"version":"3.54.6"},"reference-count":125,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T00:00:00Z","timestamp":1669766400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p><jats:italic>Pseudomonas aeruginosa<\/jats:italic> easily adapts to newer environments and acquires several genome flexibilities to overcome the effect of antibiotics during therapeutics, especially in cystic fibrosis patients. During adaptation to the host system, the bacteria employ various tactics including virulence factor production and biofilm formation to escape from the host immune system and resist antibiotics. Hence, identifying alternative strategies to combat recalcitrant pathogens is imperative for the successful elimination of drug-resistant microbes. In this context, this study portrays the anti-virulence efficacy of umbelliferone (UMB) against <jats:italic>P. aeruginosa<\/jats:italic>. UMB (7-hydroxy coumarin) is pervasively found among the plant family of <jats:italic>Umbelliferae<\/jats:italic> and <jats:italic>Asteraceae<\/jats:italic>. The UMB impeded biofilm formation in the <jats:italic>P. aeruginosa<\/jats:italic> reference strain and clinical isolates on polystyrene and glass surfaces at the concentration of 125 \u00b5g\/ml. Global proteomic analysis of UMB-treated cells revealed the downregulation of major virulence-associated proteins such as RhlR, LasA, AlgL, FliD, Tpx, HtpG, KatA, FusA1, Tsf, PhzM, PhzB2, CarB, DctP, MtnA, and MscL. A functional interaction study, gene ontology, and KEGG pathway analysis revealed that UMB could modulate the global regulators, enzymes, co-factors, and transcription factors related to quorum sensing (QS), stress tolerance, siderophore production, motility, and microcolony formation. <jats:italic>In vitro<\/jats:italic> biochemical assays further affirmed the anti-virulence efficacy of UMB by reducing pyocyanin, protease, elastase, and catalase production in various strains of <jats:italic>P. aeruginosa<\/jats:italic>. Besides the antibiofilm activity, UMB-treated cells exhibited enhanced antibiotic susceptibility to various antibiotics including amikacin, kanamycin, tobramycin, ciprofloxacin, and cefotaxime. Furthermore, <jats:italic>in vitro<\/jats:italic> cytotoxicity analysis revealed the biocompatibility of UMB, and the IC<jats:sub>50<\/jats:sub> value was determined to be 249.85 \u00b5g\/ml on the HepG2 cell line. Altogether, the study substantiates the anti-virulence efficacy of UMB against <jats:italic>P. aeruginosa<\/jats:italic>, and the proteomic analysis reveals the differential expression of the regulators related to QS, stress response, and motility factors.<\/jats:p>","DOI":"10.3389\/fcimb.2022.998540","type":"journal-article","created":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T05:29:42Z","timestamp":1669786182000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":28,"title":["Proteomic profiling spotlights the molecular targets and the impact of the natural antivirulent umbelliferone on stress response, virulence factors, and the quorum sensing network of Pseudomonas aeruginosa"],"prefix":"10.3389","volume":"12","author":[{"given":"Thirupathi","family":"Kasthuri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sivaraj","family":"Barath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muruganandam","family":"Nandhakumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunmugiah","family":"Karutha Pandian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,11,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"582","DOI":"10.3923\/ajft.2012.582.595","article-title":"Assessment of biofilm in e. coli O157: H7 and salmonella strains: influence of cultural conditions","volume":"7","author":"Adetunji","year":"2012","journal-title":"Am. J. Food Technol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1128\/AAC.00612-07","article-title":"Inhibition of quorum sensing-controlled virulence factor production in pseudomonas aeruginosa by south Florida plant extracts","volume":"52","author":"Adonizio","year":"2008","journal-title":"Antimicrob. Agents Chemother."},{"key":"B3","doi-asserted-by":"publisher","first-page":"26670","DOI":"10.1074\/jbc.273.41.26670","article-title":"Release of thioredoxin via the mechanosensitive channel MscL during osmotic downshock of escherichia coli cells","volume":"273","author":"Ajouz","year":"1998","journal-title":"J. Biol. Chem."},{"key":"B4","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1128\/JB.186.3.767-776.2004","article-title":"Direct glutaminyl-tRNA biosynthesis and indirect asparaginyl-tRNA biosynthesis in pseudomonas aeruginosa PAO1","volume":"186","author":"Akochy","year":"2004","journal-title":"J. Bacteriol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"e1008466","DOI":"10.1371\/journal.ppat.1008466","article-title":"Dissociation between the critical role of ClpB of francisella tularensis for the heat shock response and the DnaK interaction and its important role for efficient type VI secretion and bacterial virulence","volume":"16","author":"Alam","year":"2020","journal-title":"PloS Pathog."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1132","DOI":"10.1002\/iub.278","article-title":"Metabolic characteristics and importance of the universal methionine salvage pathway recycling methionine from 5\u2032-methylthioadenosine","volume":"61","author":"Albers","year":"2009","journal-title":"IUBMB Life"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.3390\/genes12071005","article-title":"Proteomics analysis reveals diverse molecular characteristics between endocardial and aortic-valvular endothelium","volume":"12","author":"Aneesh Kumar","year":"2021","journal-title":"Genes"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2011.00103","article-title":"Regulation and function of versatile aerobic and anaerobic respiratory metabolism in pseudomonas aeruginosa","volume":"2","author":"Arai","year":"2011","journal-title":"Front. Microbiol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41522-017-0015-4","article-title":"Ser\/Thr protein kinase PrkC-mediated regulation of GroEL is critical for biofilm formation in bacillus anthracis","volume":"3","author":"Arora","year":"2017","journal-title":"Microbiomes"},{"key":"B10","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1016\/j.drudis.2018.07.003","article-title":"Updates on the pathogenicity status of pseudomonas aeruginosa","volume":"24","author":"Azam","year":"2019","journal-title":"Drug Discovery Today"},{"key":"B11","doi-asserted-by":"publisher","first-page":"8375","DOI":"10.1128\/JB.187.24.8375-8384.2005","article-title":"Role of the pseudomonas fluorescens alginate lyase (AlgL) in clearing the periplasm of alginates not exported to the extracellular environment","volume":"187","author":"Bakkevig","year":"2005","journal-title":"J. Bacteriol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1642","DOI":"10.1111\/febs.12730","article-title":"Structural and kinetic studies on adenylosuccinate lyase from mycobacterium smegmatis and mycobacterium tuberculosis provide new insights on the catalytic residues of the enzyme","volume":"281","author":"Banerjee","year":"2014","journal-title":"FEBS J."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12864-019-5885-9","article-title":"Insights into klebsiella pneumoniae type VI secretion system transcriptional regulation","volume":"20","author":"Barbosa","year":"2019","journal-title":"BMC Genomics"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12934-016-0569-5","article-title":"Living together in biofilms: the microbial cell factory and its biotechnological implications","volume":"15","author":"Berlanga","year":"2016","journal-title":"Microbial Cell Factories"},{"key":"B15","doi-asserted-by":"publisher","first-page":"19","DOI":"10.2174\/157339810790820458","article-title":"Relationship between virulence factors and outcome of ventilator-associated pneumonia related to pseudomonas aeruginosa","volume":"6","author":"Berra","year":"2010","journal-title":"Curr. Respir. Med. Rev."},{"key":"B16","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1093\/clinids\/5.2.279","article-title":"Infections caused by pseudomonas aeruginosa","volume":"5","author":"Bodey","year":"1983","journal-title":"Rev. Infect. Dis."},{"key":"B17","doi-asserted-by":"publisher","first-page":"241","DOI":"10.3390\/antibiotics10030241","article-title":"Prevalence of the genes associated with biofilm and toxins synthesis amongst the pseudomonas aeruginosa clinical strains","volume":"10","author":"Bogiel","year":"2021","journal-title":"Antibiotics"},{"key":"B18","doi-asserted-by":"crossref","DOI":"10.1128\/AAC.01835-17","article-title":"Mutations in gene fusA1 as a novel mechanism of aminoglycoside resistance in clinical strains of Pseudomonas aeruginosa","volume":"62","author":"Bolard","year":"2018","journal-title":"Antimicrobial Agents and Chemotherapy"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/ncomms15853","article-title":"Francisella requires dynamic type VI secretion system and ClpB to deliver effectors for phagosomal escape","volume":"8","author":"Brodmann","year":"2017","journal-title":"Nat. Commun."},{"key":"B20","doi-asserted-by":"publisher","first-page":"4022","DOI":"10.1073\/pnas.84.12.4022","article-title":"AUU-to-AUG mutation in the initiator codon of the translation initiation factor IF3 abolishes translational autocontrol of its own gene (infC) in vivo","volume":"84","author":"Butler","year":"1987","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1436","DOI":"10.1128\/JB.01632-07","article-title":"Role of the clp system in stress tolerance, biofilm formation, and intracellular invasion in porphyromonas gingivalis","volume":"190","author":"Capestany","year":"2008","journal-title":"J. Bacteriol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1647","DOI":"10.1007\/s00726-018-2654-z","article-title":"Regulation of carbamoylphosphate synthesis in escherichia coli: an amazing metabolite at the crossroad of arginine and pyrimidine biosynthesis","volume":"50","author":"Charlier","year":"2018","journal-title":"Amino Acids"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1165","DOI":"10.1128\/JB.186.4.1165-1174.2004","article-title":"clpB, a novel member of the listeria monocytogenes CtsR regulon, is involved in virulence but not in general stress tolerance","volume":"186","author":"Chastanet","year":"2004","journal-title":"J. Bacteriol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1578","DOI":"10.1093\/nar\/gkm011","article-title":"Ribosomal protein L20 controls expression of the bacillus subtilis infC operon via a transcription attenuation mechanism","volume":"35","author":"Choonee","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.620819","article-title":"Pseudomonas aeruginosa elastase contributes to the establishment of chronic lung colonization and modulates the immune response in a murine model","volume":"11","author":"Cigana","year":"2021","journal-title":"Front. Microbiol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/S0928-8244(97)00037-0","article-title":"LasA, alkaline protease and elastase in clinical strains of pseudomonas aeruginosa: quantification by immunochemical methods","volume":"18","author":"Coin","year":"1997","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"110432","DOI":"10.1016\/j.biopha.2020.110432","article-title":"Umbelliferone (7-hydroxycoumarin): A non-toxic antidiarrheal and antiulcerogenic coumarin","volume":"129","author":"Cruz","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"B28","doi-asserted-by":"publisher","first-page":"e0144447","DOI":"10.1371\/journal.pone.0144447","article-title":"Cross-regulation between the phz1 and phz2 operons maintain a balanced level of phenazine biosynthesis in pseudomonas aeruginosa PAO1","volume":"11","author":"Cui","year":"2016","journal-title":"PloS One"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/srep08398","article-title":"Phenazine virulence factor binding to extracellular DNA is important for pseudomonas aeruginosa biofilm formation","volume":"5","author":"Das","year":"2015","journal-title":"Sci. Rep."},{"key":"B30","doi-asserted-by":"publisher","first-page":"260","DOI":"10.3390\/microorganisms8020260","article-title":"Characterization of ocular clinical isolates of pseudomonas aeruginosa from non-contact lens related keratitis patients from south India","volume":"8","author":"Dave","year":"2020","journal-title":"Microorganisms"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.758898","article-title":"Involvement of the heat shock protein HtpG of salmonella typhimurium in infection and proliferation in hosts","volume":"11","author":"Dong","year":"2021","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1034\/j.1399-3003.2000.16d30.x","article-title":"Antibiotic therapy against pseudomonas aeruginosa in cystic fibrosis: a European consensus","volume":"16","author":"D\u00f6ring","year":"2000","journal-title":"Eur. Respir. J."},{"key":"B33","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1002\/pro.3800","article-title":"Glutaminyl-tRNA synthetase from pseudomonas aeruginosa: Characterization, structure, and development as a screening platform","volume":"29","author":"Escamilla","year":"2020","journal-title":"Protein Sci."},{"key":"B34","doi-asserted-by":"publisher","first-page":"3445","DOI":"10.1099\/mic.0.042275-0","article-title":"ClgR regulation of chaperone and protease systems is essential for mycobacterium tuberculosis parasitism of the macrophage","volume":"156","author":"Estorninho","year":"2010","journal-title":"Microbiology"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1557","DOI":"10.1016\/j.chembiol.2014.08.018","article-title":"Structural and functional analysis of bacillus subtilis YisP reveals a role of its product in biofilm production","volume":"21","author":"Feng","year":"2014","journal-title":"Chem. Biol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1038\/nrmicro2907","article-title":"Adaptation of pseudomonas aeruginosa to the cystic fibrosis airway: an evolutionary perspective","volume":"10","author":"Folkesson","year":"2012","journal-title":"Nat. Rev. Microbiol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1111\/j.1574-6968.1998.tb13051.x","article-title":"Transcription of the groESL operon in pseudomonas aeruginosa PAO1","volume":"163","author":"Fujita","year":"1998","journal-title":"FEMS Microbiol. Lett."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1354","DOI":"10.1016\/j.cell.2017.10.012","article-title":"Membrane microdomain disassembly inhibits MRSA antibiotic resistance","volume":"171","author":"Garc\u00eda-Fern\u00e1ndez","year":"2017","journal-title":"Cell"},{"key":"B39","doi-asserted-by":"publisher","first-page":"101560","DOI":"10.1016\/j.jbc.2021.101560","article-title":"The pseudomonas aeruginosa homeostasis enzyme AlgL clears the periplasmic space of accumulated alginate during polymer biosynthesis","volume":"2","author":"Gheorghita","year":"2022","journal-title":"J. Biol. Chem."},{"key":"B40","doi-asserted-by":"publisher","first-page":"6025","DOI":"10.1128\/JB.00654-10","article-title":"Calcium and iron regulate swarming and type III secretion in vibrio parahaemolyticus","volume":"192","author":"Gode-Potratz","year":"2010","journal-title":"J. Bacteriol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"102235","DOI":"10.1016\/j.coph.2022.102235","article-title":"Animal models of cystic fibrosis in the era of highly effective modulator therapies","volume":"64","author":"Grubb","year":"2022","journal-title":"Curr. Opin. Pharmacol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"69","DOI":"10.2217\/fmb-2017-0111","article-title":"Effects of null mutation of the heat-shock gene htpG on the production of virulence factors by pseudomonas aeruginosa","volume":"13","author":"Grudniak","year":"2018","journal-title":"Future Microbiol."},{"key":"B43","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.ceca.2013.08.004","article-title":"Calcium homeostasis in Pseudomonas aeruginosa requires multiple transporters and modulates swarming motility","volume":"54","author":"Guragain","year":"2013","journal-title":"Cell Calcium"},{"key":"B44","article-title":"New York state infection control","volume-title":"StatPearls","author":"Habboush","year":"2021"},{"key":"B45","doi-asserted-by":"publisher","first-page":"e00568","DOI":"10.1128\/JB.00568-16","article-title":"Two isoforms of clp peptidase in pseudomonas aeruginosa control distinct aspects of cellular physiology","volume":"199","author":"Hall","year":"2017","journal-title":"J. Bacteriol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"2101032","DOI":"10.1183\/13993003.01032-2021","article-title":"Static mucus impairs bacterial clearance and allows chronic infection with pseudomonas aeruginosa in the cystic fibrosis rat","volume":"60","author":"Henderson","year":"2022","journal-title":"Eur. Respir. J."},{"key":"B47","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1111\/bcp.12356","article-title":"Targeting virulence not viability in the search for future antibacterials","volume":"79","author":"Heras","year":"2015","journal-title":"Br. J. Clin. Pharmacol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"1160","DOI":"10.1177\/1087057115591120","article-title":"Identification of chemical compounds that inhibit the function of glutamyl-tRNA synthetase from pseudomonas aeruginosa","volume":"20","author":"Hu","year":"2015","journal-title":"J. Biomol. Screen."},{"key":"B49","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1016\/j.vetmic.2014.08.014","article-title":"Identification of the clpB and bipA genes and an evaluation of their expression as related to intracellular survival for the bacterial pathogen piscirickettsia salmonis","volume":"173","author":"Isla","year":"2014","journal-title":"Vet. Microbiol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"6429","DOI":"10.1128\/IAI.73.10.6429-6436.2005","article-title":"Role of an alginate lyase for alginate transport in mucoid pseudomonas aeruginosa","volume":"73","author":"Jain","year":"2005","journal-title":"Infect. Immun."},{"key":"B51","doi-asserted-by":"publisher","first-page":"108782","DOI":"10.1016\/j.celrep.2021.108782","article-title":"Pseudomonas aeruginosa aggregates in cystic fibrosis sputum produce exopolysaccharides that likely impede current therapies","volume":"34","author":"Jennings","year":"2021","journal-title":"Cell Rep."},{"key":"B52","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1016\/j.sbi.2018.08.010","article-title":"Enzyme targets for drug design of new anti-virulence therapeutics","volume":"53","author":"Kahler","year":"2018","journal-title":"Curr. Opin. Struct. Biol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"5082","DOI":"10.1128\/IAI.00698-08","article-title":"Characterization of a unique ClpB protein of mycoplasma pneumoniae and its impact on growth","volume":"76","author":"Kannan","year":"2008","journal-title":"Infect. Immun."},{"key":"B54","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-022-09085-0","article-title":"Proteomic analysis of the periodontal pathogen prevotella intermedia secretomes in biofilm and planktonic lifestyles","volume":"12","author":"Karched","year":"2022","journal-title":"Sci. Rep."},{"key":"B55","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1016\/j.tim.2020.03.016","article-title":"Biofilm matrixome: extracellular components in structured microbial communities","volume":"28","author":"Karygianni","year":"2020","journal-title":"Trends Microbiol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00203-022-03197-x","article-title":"Rapid-killing efficacy substantiates the antiseptic property of the synergistic combination of carvacrol and nerol against nosocomial pathogens","volume":"204","author":"Kasthuri","year":"2022","journal-title":"Arch. Microbiol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"30225","DOI":"10.1074\/jbc.273.46.30225","article-title":"Elastase and the LasA protease of pseudomonas aeruginosa are secreted with their propeptides","volume":"273","author":"Kessler","year":"1998","journal-title":"J. Biol. Chem."},{"key":"B58","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.1164\/ajrccm.151.4.7697234","article-title":"Early pulmonary inflammation in infants with cystic fibrosis","volume":"151","author":"Khan","year":"1995","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B59","doi-asserted-by":"publisher","first-page":"118959","DOI":"10.1016\/j.lfs.2020.118959","article-title":"A bird eye view on cystic fibrosis: An underestimated multifaceted chronic disorder","volume":"268","author":"Kotnala","year":"2021","journal-title":"Life Sci."},{"key":"B60","doi-asserted-by":"publisher","first-page":"e0181118","DOI":"10.1371\/journal.pone.0181118","article-title":"Characterization of the molecular chaperone ClpB from the pathogenic spirochaete leptospira interrogans","volume":"12","author":"Krajewska","year":"2017","journal-title":"PloS One"},{"key":"B61","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.burnso.2021.04.001","article-title":"Detection of biofilm formation among pseudomonas aeruginosa isolated from burn patients","volume":"5","author":"Kunwar","year":"2021","journal-title":"Burns Open"},{"key":"B62","first-page":"22","article-title":"Mechanisms of antibiotic resistance in pseudomonas aeruginosa","volume":"95","author":"Lambert","year":"2002","journal-title":"J. R. Soc. Med."},{"key":"B63","doi-asserted-by":"publisher","first-page":"1053","DOI":"10.4014\/jmb.1611.11056","article-title":"Pseudomonas aeruginosa biofilm, a programmed bacterial life for fitness","volume":"27","author":"Lee","year":"2017","journal-title":"J. Microbiol. Biotechnol."},{"key":"B64","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1007\/s13238-014-0100-x","article-title":"The hierarchy quorum sensing network in pseudomonas aeruginosa","volume":"6","author":"Lee","year":"2015","journal-title":"Protein Cell"},{"key":"B65","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1016\/S0022-2836(05)80208-6","article-title":"Translated translational operator in escherichia coli auto-regulation in the infC-rpmI-rplT operon","volume":"213","author":"Lesage","year":"1990","journal-title":"J. Mol. Biol."},{"key":"B66","doi-asserted-by":"publisher","first-page":"e02318","DOI":"10.1128\/mBio.02318-17","article-title":"Pseudomonas aeruginosa AlgR phosphorylation status differentially regulates pyocyanin and pyoverdine production","volume":"9","author":"Little","year":"2018","journal-title":"MBio"},{"key":"B67","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1111\/j.1574-6968.1993.tb06450.x","article-title":"Molecular cloning and sequencing of infC, the gene encoding translation initiation factor IF3, from four enterobacterial species","volume":"112","author":"Liveris","year":"1993","journal-title":"FEMS Microbiol. Lett."},{"key":"B68","doi-asserted-by":"publisher","first-page":"3711","DOI":"10.1128\/IAI.05168-11","article-title":"Inactivation of clpB in the pathogen leptospira interrogans reduces virulence and resistance to stress conditions","volume":"79","author":"Lourdault","year":"2011","journal-title":"Infect. Immun."},{"key":"B69","doi-asserted-by":"publisher","first-page":"1562","DOI":"10.1073\/pnas.55.6.1562","article-title":"Separation of three microbial amino acid polymerization factors","volume":"55","author":"Lucas-Lenard","year":"1966","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B70","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1146\/annurev.ge.26.120192.001023","article-title":"Genetics and biogenesis of bacterial flagella","volume":"26","author":"Macnab","year":"1992","journal-title":"Annu. Rev. Genet."},{"key":"B71","doi-asserted-by":"publisher","first-page":"e00138","DOI":"10.1128\/CMR.00138-18","article-title":"Cystic fibrosis and pseudomonas aeruginosa: the host-microbe interface","volume":"32","author":"Malhotra","year":"2019","journal-title":"Clin. Microbiol. Rev."},{"key":"B72","doi-asserted-by":"publisher","first-page":"e52877","DOI":"10.1371\/journal.pone.0052877","article-title":"Functional identification of APIP as human mtnB, a key enzyme in the methionine salvage pathway","volume":"7","author":"Mary","year":"2012","journal-title":"PloS One"},{"key":"B73","doi-asserted-by":"crossref","first-page":"6454","DOI":"10.1128\/JB.183.21.6454-6465.2001","article-title":"Functional analysis of genes for biosynthesis of pyocyanin and phenazine-1-carboxamide from Pseudomonas aeruginosa PAO1","volume":"183","author":"Mavrodi","year":"2001","journal-title":"J. Bacteriology"},{"key":"B74","doi-asserted-by":"publisher","first-page":"1094","DOI":"10.1111\/mmi.14649","article-title":"ClpP1P2 peptidase activity promotes biofilm formation in pseudomonas aeruginosa","volume":"115","author":"Mawla","year":"2021","journal-title":"Mol. Microbiol."},{"key":"B75","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/S0005-2736(03)00059-2","article-title":"Protein secretion systems of pseudomonas aeruginosa and p","volume":"1611","author":"Ma","year":"2003","journal-title":"Fluorescens Biochim. Biophys. Acta (BBA) Biomembr."},{"key":"B76","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/j.bfopcu.2017.05.001","article-title":"Umbelliferone: Sources, chemistry and bioactivities review","volume":"55","author":"Mazimba","year":"2017","journal-title":"Bull. Faculty Pharmacy Cairo Univ."},{"key":"B77","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/0168-9525(90)90098-Q","article-title":"Translational control of prokaryotic gene expression","volume":"6","author":"McCarthy","year":"1990","journal-title":"Trends Genet."},{"key":"B78","doi-asserted-by":"publisher","first-page":"3073","DOI":"10.1099\/mic.0.26282-0","article-title":"Transcriptional regulation of pseudomonas aeruginosa rhlR, encoding a quorum-sensing regulatory protein","volume":"149","author":"Medina","year":"2003","journal-title":"Microbiology"},{"key":"B79","doi-asserted-by":"publisher","first-page":"e00407","DOI":"10.1128\/mBio.00407-18","article-title":"Two distinct aerobic methionine salvage pathways generate volatile methanethiol in rhodopseudomonas palustris","volume":"9","author":"Miller","year":"2018","journal-title":"MBio"},{"key":"B80","doi-asserted-by":"publisher","first-page":"e00585","DOI":"10.1128\/Spectrum.00585-21","article-title":"Time-kill evaluation of antibiotic combinations containing ceftazidime-avibactam against extensively drug-resistant pseudomonas aeruginosa and their potential role against ceftazidime-avibactam-resistant isolates","volume":"9","author":"Montero","year":"2021","journal-title":"Microbiol. Spectr."},{"key":"B81","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays","volume":"65","author":"Mosmann","year":"1983","journal-title":"J. Immunol. Methods"},{"key":"B82","doi-asserted-by":"publisher","first-page":"eaaw1629","DOI":"10.1126\/science.aaw1629","article-title":"Host monitoring of quorum sensing during pseudomonas aeruginosa infection","volume":"366","author":"Moura-Alves","year":"2019","journal-title":"Science"},{"key":"B83","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1007\/82_2015_490","article-title":"Anti-virulence strategies to target bacterial infections. how to overcome the antibiotic crisis","volume":"398","author":"M\u00fchlen","year":"2015","journal-title":"Curr. Topics Microbiol. Immunol."},{"key":"B84","doi-asserted-by":"publisher","first-page":"e1006504","DOI":"10.1371\/journal.ppat.1006504","article-title":"The RhlR quorum-sensing receptor controls pseudomonas aeruginosa pathogenesis and biofilm development independently of its canonical homoserine lactone autoinducer","volume":"13","author":"Mukherjee","year":"2017","journal-title":"PloS Pathog."},{"key":"B85","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1111\/j.1574-6976.2010.00236.x","article-title":"Tripartite ATP-independent periplasmic (TRAP) transporters in bacteria and archaea","volume":"35","author":"Mulligan","year":"2011","journal-title":"FEMS Microbiol. Rev."},{"key":"B86","doi-asserted-by":"publisher","first-page":"001458","DOI":"10.1099\/jmm.0.001458","article-title":"Invasion and diversity in pseudomonas aeruginosa urinary tract infections","volume":"71","author":"Newman","year":"2022","journal-title":"J. Med. Microbiol."},{"key":"B87","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1111\/mmi.14459","article-title":"A bifunctional salvage pathway for two distinct s-adenosylmethionine by-products that is widespread in bacteria, including pathogenic escherichia coli","volume":"113","author":"North","year":"2020","journal-title":"Mol. Microbiol."},{"key":"B88","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1016\/j.cell.2005.09.012","article-title":"GroEL1: a dedicated chaperone involved in mycolic acid biosynthesis during biofilm formation in mycobacteria","volume":"123","author":"Ojha","year":"2005","journal-title":"Cell"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2014.00082","article-title":"The pseudomonas aeruginosa AlgZR two-component system coordinates multiple phenotypes","volume":"4","author":"Okkotsu","year":"2014","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B90","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1111\/j.1469-0691.1999.tb00719.x","article-title":"Patterns and modes of \u03b2-lactam resistance in pseudomonas aeruginosa","volume":"5","author":"Pech\u00e8re","year":"1999","journal-title":"Clin. Microbiol. Infect."},{"key":"B91","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1139\/o95-115","article-title":"Translational regulation of infC operon in bacillus stearothermophilus","volume":"73","author":"Pediconi","year":"1995","journal-title":"Biochem. Cell Biol."},{"key":"B92","doi-asserted-by":"publisher","first-page":"e60228","DOI":"10.1371\/journal.pone.0060228","article-title":"Mycobacterium tuberculosis ClpP proteases are co-transcribed but exhibit different substrate specificities","volume":"8","author":"Personne","year":"2013","journal-title":"PloS One"},{"key":"B93","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41392-022-01056-1","article-title":"Pseudomonas aeruginosa: pathogenesis, virulence factors, antibiotic resistance, interaction with host, technology advances and emerging therapeutics","volume":"7","author":"Qin","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"B94","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.tim.2012.10.004","article-title":"Pyocyanin effects on respiratory epithelium: relevance in pseudomonas aeruginosa airway infections","volume":"21","author":"Rada","year":"2013","journal-title":"Trends Microbiol."},{"key":"B95","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.jacme.2013.05.001","article-title":"Effects of umbelliferone on lipid peroxidation and antioxidant status in diethylnitrosamine-induced hepatocellular carcinoma","volume":"3","author":"Ramalingam","year":"2013","journal-title":"J. Acute Med."},{"key":"B96","doi-asserted-by":"publisher","first-page":"e0151135","DOI":"10.1371\/journal.pone.0151135","article-title":"Assessment of in vivo antidiabetic properties of umbelliferone and lupeol constituents of banana (Musa sp","volume":"11","author":"Ramu","year":"2016","journal-title":"Var. Nanjangud Rasa Bale) Flower Hyperglycaemic Rodent Model. PloS One"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2018.00033","article-title":"Tripartite ATP-independent periplasmic (TRAP) transporters and tripartite tricarboxylate transporters (TTT): from uptake to pathogenicity","volume":"8","author":"Rosa","year":"2018","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B98","doi-asserted-by":"publisher","first-page":"1479","DOI":"10.1271\/bbb.67.1479","article-title":"Effects of high concentrations of inorganic salts on swarming ability in fluorescent pseudomonas strains","volume":"67","author":"Sakai","year":"2003","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"B99","doi-asserted-by":"publisher","first-page":"4780","DOI":"10.1128\/jb.175.15.4780-4789.1993","article-title":"Characterization of the pseudomonas aeruginosa alginate lyase gene (algL): cloning, sequencing, and expression in escherichia coli","volume":"175","author":"Schiller","year":"1993","journal-title":"J. Bacteriol."},{"key":"B100","doi-asserted-by":"publisher","first-page":"5357","DOI":"10.1021\/pr4007365","article-title":"Secretome of transmissible pseudomonas aeruginosa AES-1R grown in a cystic fibrosis lung-like environment","volume":"12","author":"Scott","year":"2013","journal-title":"J. Proteome Res."},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.02027","article-title":"Myrtenol attenuates MRSA biofilm and virulence by suppressing sarA expression dynamism","volume":"2027","author":"Selvaraj","year":"2019","journal-title":"Front. Microbiol."},{"key":"B102","first-page":"1104","article-title":"How microbes defend themselves from incoming hydrogen peroxide","author":"Sen","year":"2021","journal-title":"Front. Immunol."},{"key":"B103","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/j.jprot.2016.04.019","article-title":"Proteomic analysis reveals modulation of iron homeostasis and oxidative stress response in pseudomonas aeruginosa PAO1 by curcumin inhibiting quorum sensing regulated virulence factors and biofilm production","volume":"145","author":"Sethupathy","year":"2016","journal-title":"J. Proteomics"},{"key":"B104","doi-asserted-by":"publisher","first-page":"2663","DOI":"10.1128\/JB.01580-07","article-title":"Unusual properties of catalase a (KatA) of pseudomonas aeruginosa PA14 are associated with its biofilm peroxide resistance","volume":"190","author":"Shin","year":"2008","journal-title":"J. Bacteriol."},{"key":"B105","doi-asserted-by":"publisher","first-page":"163","DOI":"10.2144\/0000113924","article-title":"Streamlined extract preparation for escherichia coli-based cell-free protein synthesis by sonication or bead vortex mixing","volume":"53","author":"Shrestha","year":"2012","journal-title":"Biotechniques"},{"key":"B106","doi-asserted-by":"publisher","first-page":"364","DOI":"10.4162\/nrp.2015.9.4.364","article-title":"Anti-inflammatory and antioxidant effects of umbelliferone in chronic alcohol-fed rats","volume":"9","author":"Sim","year":"2015","journal-title":"Nutr. Res. Pract."},{"key":"B107","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1016\/j.foodchem.2009.11.022","article-title":"Umbelliferone\u2013an antioxidant isolated from acacia nilotica (L.) willd","volume":"120","author":"Singh","year":"2010","journal-title":"ex. Del. Food Chem."},{"key":"B108","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1056\/NEJMra1300109","article-title":"Origins of cystic fibrosis lung disease","volume":"372","author":"Stoltz","year":"2015","journal-title":"New Engl. J. Med."},{"key":"B109","doi-asserted-by":"publisher","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":"B110","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2019.00357","article-title":"Umbelliferone impedes biofilm formation and virulence of methicillin-resistant staphylococcus epidermidis via impairment of initial attachment and intercellular adhesion","volume":"357","author":"Swetha","year":"2019","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B111","doi-asserted-by":"publisher","first-page":"eaap9714","DOI":"10.1126\/sciadv.aap9714","article-title":"Phosphorylation decelerates conformational dynamics in bacterial translation elongation factors","volume":"4","author":"Talavera","year":"2018","journal-title":"Sci. Adv."},{"key":"B112","doi-asserted-by":"publisher","first-page":"1320","DOI":"10.1128\/iai.62.4.1320-1327.1994","article-title":"lasA and lasB genes of pseudomonas aeruginosa: analysis of transcription and gene product activity","volume":"62","author":"Toder","year":"1994","journal-title":"Infect. Immun."},{"key":"B113","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-019-50207-y","article-title":"5-dodecanolide interferes with biofilm formation and reduces the virulence of methicillin-resistant staphylococcus aureus (MRSA) through up regulation of agr system","volume":"9","author":"Valliammai","year":"2019","journal-title":"Sci. Rep."},{"key":"B114","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/ncomms11567","article-title":"Pseudomonas aeruginosa elastase cleaves a c-terminal peptide from human thrombin that inhibits host inflammatory responses","volume":"7","author":"Van Der Plas","year":"2016","journal-title":"Nat. Commun."},{"key":"B115","doi-asserted-by":"publisher","first-page":"465","DOI":"10.2217\/fmb-2021-0158","article-title":"Pathogenic arsenal of pseudomonas aeruginosa: an update on virulence factors","volume":"17","author":"Veetilvalappil","year":"2022","journal-title":"Future Microbiol."},{"key":"B116","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1007\/s00203-007-0292-z","article-title":"Growth, osmotic downshock resistance and differentiation of bacillus subtilis strains lacking mechanosensitive channels","volume":"189","author":"Wahome","year":"2008","journal-title":"Arch. Microbiol."},{"key":"B117","doi-asserted-by":"publisher","first-page":"2095","DOI":"10.1097\/CCM.0b013e3181f265ba","article-title":"Anti-infective external coating of central venous catheters: a randomized, noninferiority trial comparing 5-fluorouracil with chlorhexidine\/silver sulfadiazine in preventing catheter colonization","volume":"38","author":"Walz","year":"2010","journal-title":"Crit. Care Med."},{"key":"B118","doi-asserted-by":"crossref","first-page":"439","DOI":"10.3389\/fmicb.2019.00439","article-title":"Oxidized OxyR up-regulates ahpCF expression to suppress plating defects of oxyR-and catalase-deficient strains","volume":"10","author":"Wan","year":"2019","journal-title":"Front. Microbiol."},{"key":"B119","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.dnarep.2016.09.001","article-title":"Transcription-associated mutation of lasR in pseudomonas aeruginosa","volume":"46","author":"Wang","year":"2016","journal-title":"DNA Repair"},{"key":"B120","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1016\/j.chembiol.2016.01.006","article-title":"Chemical genetics reveals environment-specific roles for quorum sensing circuits in pseudomonas aeruginosa","volume":"23","author":"Welsh","year":"2016","journal-title":"Cell Chem. Biol."},{"key":"B121","doi-asserted-by":"publisher","first-page":"1715","DOI":"10.1099\/13500872-141-7-1715","article-title":"Functional analysis of the flagellar genes in the fliD operon of salmonella typhimurium","volume":"141","author":"Yokoseki","year":"1995","journal-title":"Microbiology"},{"key":"B122","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1471-2180-12-85","article-title":"A fur-like protein PerR regulates two oxidative stress response related operons dpr and metQIN in streptococcus suis","volume":"12","author":"Zhang","year":"2012","journal-title":"BMC Microbiol."},{"key":"B123","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1111\/jfd.13571","article-title":"The role of dctP gene in regulating colonization, adhesion and pathogenicity of vibrio alginolyticus strain HY9901","volume":"45","author":"Zhang","year":"2022","journal-title":"J. Fish Dis."},{"key":"B124","doi-asserted-by":"publisher","first-page":"e1002449","DOI":"10.1371\/journal.pbio.1002449","article-title":"Structural and molecular mechanism of CdpR involved in quorum-sensing and bacterial virulence in pseudomonas aeruginosa","volume":"14","author":"Zhao","year":"2016","journal-title":"PloS Biol."},{"key":"B125","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12866-015-0555-9","article-title":"Molecular study on the carAB operon reveals that carB gene is required for swimming and biofilm formation in xanthomonas citri subsp","volume":"15","author":"Zhuo","year":"2015","journal-title":"citri. BMC Microbiol."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2022.998540\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T05:29:51Z","timestamp":1669786191000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2022.998540\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,30]]},"references-count":125,"alternative-id":["10.3389\/fcimb.2022.998540"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2022.998540","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,30]]},"article-number":"998540"}}