{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T20:02:02Z","timestamp":1793908922807,"version":"4.8.0"},"reference-count":103,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T00:00:00Z","timestamp":1753056000000},"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. Microbiol."],"abstract":"<jats:p>\n                    <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                    (\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    ) is a ubiquitous opportunistic pathogen and a major cause of nosocomial infections worldwide. It can provoke a spectrum of clinical manifestations-ranging from postoperative wound infections, pressure ulcers, abscesses, and otitis media to life-threatening bacteremia and sepsis, especially in burn patients. Over the past decade, extensive research has elucidated its complex virulence repertoire, including exotoxins, proteases, and siderophores; the hierarchical Quorum Sensing (QS) networks; and its robust capacity for biofilm formation. In this review, we consolidate significant studies published since 2015 to develop a comprehensive framework elucidating the virulence mechanisms of\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    . Beyond cataloging individual factors, we highlight how QS regulators coordinate toxin production and biofilm maturation, and how these processes converge to facilitate immune evasion. We further examine cross-talk between QS circuits (Las, Rhl, and Pqs), their response to environmental cues, and the modulatory role of host signals. Despite these advances, significant gaps remain: the spatiotemporal interplay among different virulence modules; the precise molecular triggers of biofilm dispersal; and the dynamics of bacterial\u2013host immune interactions\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Notably, targeting QS with small-molecule inhibitors has shown promise in attenuating pathogenicity, yet translating these findings into clinical therapies requires more nuanced understanding of resistance emergence and host microbiome effects. We propose that future investigations prioritize (1) the structural biology of QS receptors to guide rational inhibitor design; (2) single-cell and organ-on-a-chip models to dissect biofilm heterogeneity; (3) dual-omics approaches to map host\u2013pathogen signaling crosstalk; and (4) environmental modulators-such as iron availability and shear stress-that fine-tune virulence expression. Such multidisciplinary efforts will underpin the development of next-generation anti-virulence therapies, ultimately improving prevention and treatment of\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    infections and safeguarding public health.\n                  <\/jats:p>","DOI":"10.3389\/fmicb.2025.1619626","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T05:22:47Z","timestamp":1753075367000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":64,"title":["A comprehensive review of the pathogenic mechanisms of Pseudomonas aeruginosa: synergistic effects of virulence factors, quorum sensing, and biofilm formation"],"prefix":"10.3389","volume":"16","author":[{"given":"Xindan","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duo","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinlong","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiming","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,21]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2752","DOI":"10.3389\/fmicb.2018.02752","article-title":"Role of the multidrug resistance efflux pump MexCD-OprJ in the P. aeruginosa quorum sensing response","volume":"9","author":"Alcalde-Rico","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"140119","DOI":"10.1016\/j.ijbiomac.2025.140119","article-title":"Optimized peptide inhibitor Aqs1C targets LasR to disrupt quorum sensing and biofilm formation in Pseudomonas aeruginosa: insights from MD simulations and in vitro studies","volume":"300","author":"Alhadrami","year":"2025","journal-title":"Int. J. Biol. Macromol."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1111\/mmi.14617","article-title":"Cell-type-specific hypertranslocation of effectors by the P. aeruginosa type III secretion system","volume":"115","author":"Armentrout","year":"2021","journal-title":"Mol. Microbiol."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1080\/15376516.2018.1429038","article-title":"Pyocyanin induces systemic oxidative stress, inflammation and behavioral changes in vivo","volume":"28","author":"Arora","year":"2018","journal-title":"Toxicol. Mech. Methods"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"121","DOI":"10.3390\/v14010121","article-title":"Outer membrane vesicles (OMVs) of P. aeruginosa provide passive resistance but not sensitization to LPS-specific phages","volume":"14","author":"Augustyniak","year":"2022","journal-title":"Viruses"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"e0086021","DOI":"10.1128\/mBio.00860-21","article-title":"O-specific antigen-dependent surface hydrophobicity mediates aggregate assembly type in Pseudomonas aeruginosa","volume":"12","author":"Azimi","year":"2021","journal-title":"MBio"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"4810217","DOI":"10.1155\/2019\/4810217","article-title":"Efficacy of Artesunate against P. aeruginosa biofilm mediated by Iron","volume":"2019","author":"Bao","year":"2019","journal-title":"Biomed. Res. Int."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"5086","DOI":"10.1128\/IAI.02315-14","article-title":"FNR regulates expression of important virulence factors contributing to pathogenicity of uropathogenic Escherichia coli","volume":"82","author":"Barbieri","year":"2014","journal-title":"Infect. Immun."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"2331","DOI":"10.1111\/j.1462-2920.2008.01658.x","article-title":"Roles of type IV pili, flagellum-mediated motility and extracellular DNA in the formation of mature multicellular structures in P. aeruginosa biofilms","volume":"10","author":"Barken","year":"2008","journal-title":"Environ. Microbiol."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"10723","DOI":"10.1021\/nn5044383","article-title":"Nanoscale adhesion forces of P. aeruginosa type IV pili","volume":"8","author":"Beaussart","year":"2014","journal-title":"ACS Nano"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.3390\/pathogens11091015","article-title":"Relationship between biofilm-formation, phenotypic virulence factors and antibiotic resistance in environmental Pseudomonas aeruginosa","volume":"11","author":"Behzadi","year":"2022","journal-title":"Pathogens"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1128\/ecosalplus.ESP-0001-2018","article-title":"Function and biogenesis of lipopolysaccharides","volume":"8","author":"Bertani","year":"2018","journal-title":"EcoSal Plus"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1186\/s12890-016-0339-5","article-title":"Cystic fibrosis lung environment and Pseudomonas aeruginosa infection","volume":"16","author":"Bhagirath","year":"2016","journal-title":"BMC Pulm. Med."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1111\/j.1365-2958.2009.06782.x","article-title":"The GacS\/GacA signal transduction system of P. aeruginosa acts exclusively through its control over the transcription of the RsmY and RsmZ regulatory small RNAs","volume":"73","author":"Brencic","year":"2009","journal-title":"Mol. Microbiol."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1745","DOI":"10.1084\/jem.20100257","article-title":"Redundant roles for inflammasome receptors NLRP3 and NLRC4 in host defense against Salmonella","volume":"207","author":"Broz","year":"2010","journal-title":"J. Exp. Med."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.1021\/acsinfecdis.8b00112","article-title":"The therapeutic pipeline for P. aeruginosa infections. ACS","volume":"4","author":"Burrows","year":"2018","journal-title":"Infect. Dis."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"6535","DOI":"10.3390\/molecules28186535","article-title":"Development of Quinazolinone derivatives as modulators of virulence factors of Pseudomonas aeruginosa cystic fibrosis strains","volume":"28","author":"Carullo","year":"2023","journal-title":"Molecules"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"135588","DOI":"10.1016\/j.jhazmat.2024.135588","article-title":"Bacterial outer membrane vesicles increase polymyxin resistance in P. aeruginosa while inhibiting its quorum sensing","volume":"478","author":"Chen","year":"2024","journal-title":"J. Hazard. Mater."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"3066","DOI":"10.1111\/odi.14776","article-title":"SHED-exos promote saliva secretion by suppressing p-ERK1\/2-mediated apoptosis in glandular cells","volume":"30","author":"Chu","year":"2024","journal-title":"Oral Dis."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"e0058020","DOI":"10.1128\/jb.00580-21","article-title":"Direct inhibition of RetS synthesis by RsmA contributes to homeostasis of the P. aeruginosa Gac\/Rsm signaling system","volume":"204","author":"Corley","year":"2022","journal-title":"J. Bacteriol."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"13502","DOI":"10.1074\/jbc.RA119.009934","article-title":"Exposure of P. aeruginosa to bactericidal hypochlorous acid during neutrophil phagocytosis is compromised in cystic fibrosis","volume":"294","author":"Dickerhof","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1038\/s41564-018-0109-7","article-title":"Pore-forming activity of the P. aeruginosa type III secretion system translocon alters the host epigenome","volume":"3","author":"Dortet","year":"2018","journal-title":"Nat. Microbiol."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"5113","DOI":"10.3389\/fmicb.2021.765113","article-title":"Genomic characterization of Carbapenem-non-susceptible P. aeruginosa clinical isolates from Saudi Arabia revealed a global dissemination of GES-5-producing ST235 and VIM-2-producing ST233 sub-lineages","volume":"12","author":"Doumith","year":"2022","journal-title":"Front. Microbiol."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1007\/s11306-020-01658-2","article-title":"New markers for sepsis caused by P. aeruginosa during burn infection","volume":"16","author":"Elmassry","year":"2020","journal-title":"Metabolomics"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"3655","DOI":"10.3390\/polym14173655","article-title":"Attenuation of P. aeruginosa quorum sensing virulence of biofilm and Pyocyanin by mBTL-loaded calcium alginate nanoparticles","volume":"14","author":"Eltayb","year":"2022","journal-title":"Polymers"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"7676","DOI":"10.1021\/jacs.1c13653","article-title":"Azetidomonamide and Diazetidomonapyridone metabolites control biofilm formation and pigment synthesis in Pseudomonas aeruginosa","volume":"144","author":"Ernst","year":"2022","journal-title":"J. Am. Chem. Soc."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1164\/rccm.202004-1322OC","article-title":"Sustained coinfections with Staphylococcus aureus and Pseudomonas aeruginosa in cystic fibrosis","volume":"203","author":"Fischer","year":"2021","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"5754","DOI":"10.3389\/fcimb.2022.835754","article-title":"Contribution of P. aeruginosa exopolysaccharides Pel and Psl to wound infections","volume":"12","author":"Fleming","year":"2022","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref29","author":"Foulkes","year":"2022"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"1578","DOI":"10.1021\/acs.jcim.3c00064","article-title":"Structural insights into P. aeruginosa exotoxin a-elongation factor 2 interactions: A molecular dynamics study","volume":"63","author":"Gholami","year":"2023","journal-title":"J. Chem. Inf. Model."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"664","DOI":"10.3390\/microorganisms11030664","article-title":"P. aeruginosa and the complement system: a review of the evasion strategies","volume":"11","author":"Gonz\u00e1lez-Alsina","year":"2023","journal-title":"Microorganisms"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"17659","DOI":"10.3390\/molecules200917659","article-title":"Small-molecule inhibitors of the type III secretion system","volume":"20","author":"Gu","year":"2015","journal-title":"Molecules"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"e02762","DOI":"10.1128\/AEM.02762-17","article-title":"Aeruginosa biofilm antibiotic resistance gene ndvB expression requires the RpoS stationary-phase sigma factor","volume":"84","author":"Hall","year":"2018","journal-title":"Appl. Environ. Microbiol."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1186\/s12866-024-03249-w","article-title":"In vitro investigation of relationship between quorum-sensing system genes, biofilm forming ability, and drug resistance in clinical isolates of Pseudomonas aeruginosa","volume":"24","author":"Hemmati","year":"2024","journal-title":"BMC Microbiol."},{"key":"ref35","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-52732-5","article-title":"PlzR regulates type IV pili assembly in P. aeruginosa via PilZ binding","volume":"15","author":"Hendrix","year":"2024","journal-title":"Nat. Commun."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1097\/QCO.0000000000000768","article-title":"Predictors of multidrug resistant P. aeruginosa involvement in bloodstream infections","volume":"34","author":"Herrera","year":"2021","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"e221","DOI":"10.1093\/infdis\/jiad457","article-title":"Antibody-mediated serum resistance Protects P. aeruginosa during bloodstream infections","volume":"230","author":"Hickson","year":"2024","journal-title":"J. Infect. Dis."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"1800538","DOI":"10.2807\/1560-7917.ES.2019.24.33.1800538","article-title":"EARS-net participants. Strong correlation between the rates of intrinsically antibiotic-resistant species and the rates of acquired resistance in gram-negative species causing bacteraemia, EU\/EEA, 2016","volume":"24","author":"Jarlier","year":"2019","journal-title":"Euro Surveill."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1165\/rcmb.2008-0408OC","article-title":"TLR-4-mediated innate immunity is reduced in cystic fibrosis airway cells","volume":"42","author":"John","year":"2010","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"1246","DOI":"10.1126\/science.1240248","article-title":"Non-canonical Inflammasome activation by intracellular LPS independent of TLR4","volume":"341","author":"Kayagaki","year":"2013","journal-title":"Science"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/j.cell.2018.09.020","article-title":"Bacterial Siderophores promote animal host Iron acquisition and growth","volume":"175","author":"Kim","year":"2018","journal-title":"Cell"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"16985","DOI":"10.1073\/pnas.2010996117","article-title":"Atomic structure of the Campylobacter jejuni flagellar filament reveals how \u03b5 Proteobacteria escaped toll-like receptor 5 surveillance","volume":"117","author":"Kreutzberger","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"e1010306","DOI":"10.1371\/journal.ppat.1010306","article-title":"Exotoxin S secreted by internalized P. aeruginosa delays lytic host cell death","volume":"18","author":"Kroken","year":"2022","journal-title":"PLoS Pathog."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"e02644","DOI":"10.1128\/mBio.02644-19","article-title":"Social cooperativity of Bacteria during reversible surface attachment in young biofilms: a quantitative comparison of P. aeruginosa PA14 and PAO1","volume":"11","author":"Lee","year":"2020","journal-title":"MBio"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"926758","DOI":"10.3389\/fcimb.2022.926758","article-title":"Virulence factors of Pseudomonas aeruginosa and antivirulence strategies to combat its drug resistance","volume":"12","author":"Liao","year":"2022","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"105085","DOI":"10.1016\/j.micpath.2021.105085","article-title":"Distribution of type VI secretion system (T6SS) in clinical Klebsiella pneumoniae strains from a Chinese hospital and its potential relationship with virulence and drug resistance","volume":"162","author":"Liao","year":"2022","journal-title":"Microb. Pathog."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"6684","DOI":"10.1038\/s41467-022-34607-9","article-title":"Autoinducer-2 and bile salts induce c-di-GMP synthesis to repress the T3SS via a T3SS chaperone","volume":"13","author":"Li","year":"2022","journal-title":"Nat. Commun."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"107915","DOI":"10.1016\/j.biotechadv.2022.107915","article-title":"Biofilm control by interfering with c-di-GMP metabolism and signaling","volume":"56","author":"Liu","year":"2022","journal-title":"Biotechnol. Adv."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"1406","DOI":"10.1038\/s41589-024-01740-z","article-title":"Chemical signaling in biofilm-mediated biofouling","volume":"20","author":"Liu","year":"2024","journal-title":"Nat. Chem. Biol."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.3389\/fmicb.2020.01096","article-title":"ClpV3 of the H3-type VI secretion system (H3-T6SS) affects multiple virulence factors in Pseudomonas aeruginosa","volume":"11","author":"Li","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1007\/978-3-031-08491-1_2","article-title":"Iron homeostasis in Pseudomonas aeruginosa: targeting Iron acquisition and storage as an antimicrobial strategy","volume":"1386","author":"Llamas","year":"2022","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"854507","DOI":"10.1155\/2015\/854507","article-title":"Th1 and Th17 cells in tuberculosis: protection, pathology, and biomarkers","volume":"2015","author":"Lyadova","year":"2015","journal-title":"Mediat. Inflamm."},{"key":"ref55","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1517\/14728222.2014.855199","article-title":"Targeting the type III secretion system to treat bacterial infections","volume":"18","author":"Marshall","year":"2013","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"685","DOI":"10.9771\/cmbio.v22i4.53209","article-title":"Biofilm formation and virulence factors distribution among clinical isolates of Pseudomonas aeruginosa","volume":"22","author":"Mauad","year":"2023","journal-title":"Rev. Ci\u00ean M\u00e9d. Biol."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1021\/acsptsci.3c00354","article-title":"Juglone as a natural quorum sensing inhibitor against Pseudomonas aeruginosa pqs-mediated virulence and biofilms","volume":"7","author":"Ma","year":"2024","journal-title":"ACS Pharmacol Transl Sci."},{"key":"ref57","doi-asserted-by":"publisher","DOI":"10.1038\/nmicrobiol.2017.27","article-title":"Cyclic-di-GMP regulates lipopolysaccharide modification and contributes to P. aeruginosa immune evasion","volume":"2","author":"McCarthy","year":"2017","journal-title":"Nat. Microbiol."},{"key":"ref58","doi-asserted-by":"publisher","first-page":"e1007820","DOI":"10.1371\/journal.ppat.1007820","article-title":"An autoinducer-independent RhlR quorum-sensing receptor enables analysis of RhlR regulation","volume":"15","author":"McCready","year":"2019","journal-title":"PLoS Pathog."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"291","DOI":"10.3389\/fmicb.2016.00291","article-title":"A putative ABC transporter Permease is necessary for resistance to acidified nitrite and EDTA in Pseudomonas aeruginosa under aerobic and anaerobic planktonic and biofilm conditions","volume":"7","author":"McDaniel","year":"2016","journal-title":"Front. Microbiol."},{"key":"ref60","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1007\/978-3-031-08491-1_4","article-title":"aeruginosa Quorum Sensing","volume":"1386","author":"Miranda","year":"2022","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref61","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1186\/s13568-021-01332-3","article-title":"ADP-ribosyl transferase activity and gamma radiation cytotoxicity of P. aeruginosa exotoxin a","volume":"11","author":"Morgan","year":"2021","journal-title":"AMB Express"},{"key":"ref62","doi-asserted-by":"publisher","first-page":"31","DOI":"10.4155\/tde-2022-0055","article-title":"New insights on P. aeruginosa exotoxin A-based immunotoxins in targeted cancer therapeutic delivery","volume":"14","author":"Morgan","year":"2023","journal-title":"Ther. Deliv."},{"key":"ref63","doi-asserted-by":"publisher","first-page":"10114","DOI":"10.1038\/ncomms10114","article-title":"Structure of a bacterial type III secretion system in contact with a host membrane in situ","volume":"6","author":"Nans","year":"2015","journal-title":"Nat. Commun."},{"key":"ref64","doi-asserted-by":"publisher","first-page":"2718","DOI":"10.3390\/microorganisms11112718","article-title":"T6SS: a key to Pseudomonas\u2019s success in biocontrol?","volume":"11","author":"Navarro-Monserrat","year":"2023","journal-title":"Microorganisms."},{"key":"ref65","doi-asserted-by":"publisher","first-page":"409","DOI":"10.3390\/antibiotics12020409","article-title":"Trends in P. aeruginosa (P. aeruginosa) bacteremia during the COVID-19 pandemic: a systematic review","volume":"12","author":"Ng","year":"2023","journal-title":"Antibiotics"},{"key":"ref66","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1007\/s00284-023-03467-x","article-title":"Prevalence of type III secretion system (T3SS) and biofilm development in genetically heterogeneous clinical isolates of P. aeruginosa from Nigeria","volume":"80","author":"Olaniran","year":"2023","journal-title":"Curr. Microbiol."},{"key":"ref67","doi-asserted-by":"publisher","first-page":"159","DOI":"10.3390\/antibiotics13020159","article-title":"Outbreak of P. aeruginosa high-risk clone ST309 serotype O11 featuring blaPER-1 and qnrVC6","volume":"13","author":"Papa-Ezdra","year":"2024","journal-title":"Antibiotics"},{"key":"ref68","first-page":"641","article-title":"Aeruginosa lipopolysaccharide: a major virulence factor, initiator of inflammation and target for effective immunity","volume-title":"Int. J. Med. Microbiol.Int. J. Med. Microbiol.","author":"Pier","year":"2007"},{"key":"ref69","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1177\/1087057116629923","article-title":"Identification of inhibitors of P. aeruginosa exotoxin-S ADP-Ribosyltransferase activity","volume":"21","author":"Pinto","year":"2016","journal-title":"J. Biomol. Screen."},{"key":"ref71","doi-asserted-by":"publisher","first-page":"199","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":"ref70","doi-asserted-by":"publisher","first-page":"153374","DOI":"10.1016\/j.scitotenv.2022.153374","article-title":"Metabolism differences of biofilm and planktonic P. aeruginosa in viable but non-culturable state induced by chlorine stress","volume":"821","author":"Qi","year":"2022","journal-title":"Sci. Total Environ."},{"key":"ref72","doi-asserted-by":"publisher","first-page":"10","DOI":"10.3390\/pathogens6010010","article-title":"Interactions between neutrophils and P. aeruginosa in cystic fibrosis","volume":"6","author":"Rada","year":"2017","journal-title":"Pathogens"},{"key":"ref73","doi-asserted-by":"publisher","first-page":"1","DOI":"10.33865\/wjb.007.03.0516","article-title":"Biofilm formation and its regulation by extracellular appendages in Pseudomonas aeruginosa","volume":"7","author":"Ramzan","year":"2022","journal-title":"World J. Biol. Biotechnol."},{"key":"ref9001","doi-asserted-by":"publisher","first-page":"e7259","DOI":"10.1371\/journal.pone.0007259","article-title":"Pseudomonas aeruginosa LPS or flagellin are sufficient to activate TLR-dependent signaling in murine alveolar macrophages and airway epithelial cells","volume":"4","author":"Raoust","year":"2009","journal-title":"PLoS One."},{"key":"ref74","doi-asserted-by":"publisher","first-page":"759348","DOI":"10.1155\/2015\/759348","article-title":"The formation of biofilms by Pseudomonas aeruginosa: a review of the natural and synthetic compounds interfering with control mechanisms","volume":"2015","author":"Rasamiravaka","year":"2015","journal-title":"Biomed. Res. Int."},{"key":"ref75","doi-asserted-by":"publisher","first-page":"e0123805","DOI":"10.1371\/journal.pone.0123805","article-title":"Global regulator MorA affects virulence-associated protease secretion in P. aeruginosa PAO1","volume":"10","author":"Ravichandran","year":"2015","journal-title":"PLoS One"},{"key":"ref76","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1016\/j.ijantimicag.2018.03.018","article-title":"Bacteraemia due to extensively drug-resistant P. aeruginosa sequence type 235 high-risk clone: facing the perfect storm","volume":"52","author":"Recio","year":"2018","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref77","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1128\/jb.187.1.276-285.2005","article-title":"Posttranscriptional repression of GacS\/GacA-controlled genes by the RNA-binding protein RsmE acting together with RsmA in the biocontrol strain Pseudomonas fluorescens CHA0","volume":"187","author":"Reimmann","year":"2005","journal-title":"J. Bacteriol."},{"key":"ref78","doi-asserted-by":"publisher","first-page":"2505","DOI":"10.3389\/fmicb.2022.1042505","article-title":"Diversity and prevalence of type VI secretion system effectors in clinical P. aeruginosa isolates","volume":"13","author":"Robinson","year":"2023","journal-title":"Front. Microbiol."},{"key":"ref79","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1038\/s41579-020-00477-5","article-title":"P. aeruginosa adaptation and evolution in patients with cystic fibrosis","volume":"19","author":"Rossi","year":"2021","journal-title":"Nat. Rev. Microbiol."},{"key":"ref80","doi-asserted-by":"publisher","first-page":"2114","DOI":"10.1128\/AAC.05574-11","article-title":"Hypoxia increases antibiotic resistance in P. aeruginosa through altering the composition of multidrug efflux pumps","volume":"56","author":"Schaible","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref81","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-08733-w","article-title":"Phenazine production promotes antibiotic tolerance and metabolic heterogeneity in P. aeruginosa biofilms","volume":"10","author":"Schiessl","year":"2019","journal-title":"Nat. Commun."},{"key":"ref82","doi-asserted-by":"publisher","first-page":"291","DOI":"10.3390\/pathogens8040291","article-title":"Genetic basis and physiological effects of lipid a hydroxylation in P. aeruginosa PAO1","volume":"8","author":"Sciuto","year":"2019","journal-title":"Pathogens"},{"key":"ref83","doi-asserted-by":"publisher","first-page":"1235","DOI":"10.1007\/s15010-024-02313-x","article-title":"Impact of multidrug resistance on the virulence and fitness of Pseudomonas aeruginosa: a microbiological and clinical perspective","volume":"52","author":"Sendra","year":"2024","journal-title":"Infection"},{"key":"ref84","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-021-05969-0","article-title":"Isolation and characterizations of a novel recombinant scFv antibody against exotoxin a of Pseudomonas aeruginosa","volume":"21","author":"Shadman","year":"2021","journal-title":"BMC Infect. Dis."},{"key":"ref85","doi-asserted-by":"publisher","first-page":"13","DOI":"10.4103\/mj.mj_11_21","article-title":"Effect biofilm formation in P. aeruginosa resistance to antibiotic","volume":"21","author":"Shatti","year":"2022","journal-title":"Mustansiriya Med. J."},{"key":"ref86","doi-asserted-by":"publisher","first-page":"e0126922","DOI":"10.1128\/spectrum.01269-22","article-title":"Evidence for complex interplay between quorum sensing and antibiotic resistance in Pseudomonas aeruginosa","volume":"10","author":"Sikdar","year":"2022","journal-title":"Microbiol Spectr."},{"key":"ref87","doi-asserted-by":"publisher","first-page":"100051","DOI":"10.1016\/j.engmic.2022.100051","article-title":"Two-component system GacS\/GacA, a global response regulator of bacterial physiological behaviors","volume":"3","author":"Song","year":"2023","journal-title":"Engineer. Microbiol."},{"key":"ref88","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.hlife.2023.02.001","article-title":"Emergence of hypervirulent P. aeruginosa pathotypically armed with co-expressed T3SS effectors ExoS and ExoU","volume":"1","author":"Song","year":"2023","journal-title":"hLife"},{"key":"ref89","doi-asserted-by":"publisher","first-page":"102984","DOI":"10.1016\/j.ebiom.2020.102984","article-title":"The P. aeruginosa protease LasB directly activates IL-1\u03b2","volume":"60","author":"Sun","year":"2020","journal-title":"EBioMedicine"},{"key":"ref90","doi-asserted-by":"publisher","first-page":"3","DOI":"10.3390\/antibiotics10010003","article-title":"Biofilms as promoters of bacterial antibiotic resistance and tolerance","volume":"10","author":"Uru\u00e9n","year":"2020","journal-title":"Antibiotics"},{"key":"ref91","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1111\/j.1574-6976.2005.00012.x","article-title":"Regulation of quorum sensing in Pseudomonas","volume":"30","author":"Venturi","year":"2006","journal-title":"FEMS Microbiol. Rev."},{"key":"ref92","doi-asserted-by":"publisher","first-page":"fny201","DOI":"10.1093\/femsle\/fny201","article-title":"Bacterial type III secretion systems: a complex device for the delivery of bacterial effector proteins into eukaryotic host cells","volume":"365","author":"Wagner","year":"2018","journal-title":"FEMS Microbiol. Lett."},{"key":"ref93","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.actbio.2024.07.028","article-title":"Escherichia coli exopolysaccharides disrupt P. aeruginosa biofilm and increase its antibiotic susceptibility","volume":"185","author":"Wan","year":"2024","journal-title":"Acta Biomater."},{"key":"ref94","doi-asserted-by":"publisher","first-page":"108957","DOI":"10.1016\/j.celrep.2021.108957","article-title":"P. aeruginosa T6SS-mediated molybdate transport contributes to bacterial competition during anaerobiosis","volume":"35","author":"Wang","year":"2021","journal-title":"Cell Rep."},{"key":"ref95","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1111\/j.1574-6968.2007.00773.x","article-title":"Examination of P. aeruginosa lasI regulation and 3-oxo-C12-homoserine lactone production using a heterologous Escherichia coli system","volume":"273","author":"Wargo","year":"2007","journal-title":"FEMS Microbiol. Lett."},{"key":"ref96","doi-asserted-by":"publisher","first-page":"1332","DOI":"10.1038\/ismej.2011.13","article-title":"Cooperation and cheating in Pseudomonas aeruginosa: the roles of the las, rhl and pqs quorum-sensing systems","volume":"5","author":"Wilder","year":"2011","journal-title":"ISME J."},{"key":"ref97","doi-asserted-by":"publisher","first-page":"L1015","DOI":"10.1152\/ajplung.00158.2016","article-title":"IL-17A-mediated expression of epithelial IL-17C promotes inflammation during acute P. aeruginosa pneumonia","volume":"311","author":"Wolf","year":"2016","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref98","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.micres.2008.10.001","article-title":"The effect of c-di-GMP (3\u2032-5\u2032-cyclic diguanylic acid) on the biofilm formation and adherence of Streptococcus mutans","volume":"165","author":"Yan","year":"2010","journal-title":"Microbiol. Res."},{"key":"ref99","doi-asserted-by":"publisher","first-page":"e02292","DOI":"10.1128\/AAC.02292-16","article-title":"Real-time monitoring of nfxB mutant occurrence and dynamics in P. aeruginosa biofilm exposed to subinhibitory concentrations of ciprofloxacin","volume":"61","author":"Zaborskyte","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref100","doi-asserted-by":"publisher","first-page":"6627","DOI":"10.1128\/AEM.02184-14","article-title":"The two-component GacS-GacA system activates lipA translation by RsmE but not RsmA in Pseudomonas protegens Pf-5","volume":"80","author":"Zha","year":"2014","journal-title":"Appl. Environ. Microbiol."},{"key":"ref101","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.ijantimicag.2018.03.002","article-title":"Can the quorum sensing inhibitor resveratrol function as an aminoglycoside antibiotic accelerant against Pseudomonas aeruginosa?","volume":"52","author":"Zhou","year":"2018","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref103","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1038\/s41419-020-2672-0","article-title":"Brd4 inhibition ameliorates Pyocyanin-mediated macrophage dysfunction via transcriptional repression of reactive oxygen and nitrogen free radical pathways","volume":"11","author":"Zhu","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref102","doi-asserted-by":"publisher","first-page":"e665","DOI":"10.1016\/s2666-5247(23)00113-1","article-title":"The epidemiology and virulence of carbapenem-resistant P. aeruginosa in China","volume":"4","author":"Zhu","year":"2023","journal-title":"Lancet Microbe"}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2025.1619626\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T05:22:48Z","timestamp":1753075368000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2025.1619626\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,21]]},"references-count":103,"alternative-id":["10.3389\/fmicb.2025.1619626"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2025.1619626","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,21]]},"article-number":"1619626"}}