Interplay between biofilm microenvironment and pathogenicity of Pseudomonas aeruginosa in cystic fibrosis lung chronic infection

Biofilm - Tập 4 - Trang 100089 - 2022
Olivier Guillaume1,2, Cosmin Butnarasu3, Sonja Visentin3, Erik Reimhult4
13D Printing and Biofabrication Group, Institute of Materials Science and Technology, TU Wien (Technische Universität Wien), Getreidemarkt 9/308, 1060, Vienna, Austria
2Austrian Cluster for Tissue Regeneration, Austria
3Department of Molecular Biotechnology and Health Science, University of Turin, Turin, 10135, Italy
4Institute of Biologically Inspired Materials, Department of Nanobiotechnology, University of Natural Resources and Life Sciences Vienna, Muthgasse 11, 1190, Vienna, Austria

Tài liệu tham khảo

Hilker, 2015, Interclonal gradient of virulence in the Pseudomonas aeruginosa pangenome from disease and environment, Environ Microbiol, 17, 29, 10.1111/1462-2920.12606 Walters, 2007, Epidemiology of cystic fibrosis, 21 Jennings, 2021, Pseudomonas aeruginosa aggregates in cystic fibrosis sputum produce exopolysaccharides that likely impede current therapies, Cell Rep, 34, 10.1016/j.celrep.2021.108782 Høiby, 2011, Recent advances in the treatment of Pseudomonas aeruginosa infections in cystic fibrosis, BMC Med, 9, 32, 10.1186/1741-7015-9-32 Rau, 2010, Early adaptive developments of Pseudomonas aeruginosa after the transition from life in the environment to persistent colonization in the airways of human cystic fibrosis hosts, Environ Microbiol, 12, 1643, 10.1111/j.1462-2920.2010.02211.x Barclay, 1996, Adaptive resistance to tobramycin in Pseudomonas aeruginosa lung infection in cystic fibrosis, J Antimicrob Chemother, 37, 1155, 10.1093/jac/37.6.1155 Fernández, 2010, Adaptive resistance to the “last hope” antibiotics polymyxin B and colistin in Pseudomonas aeruginosa is mediated by the novel two-component regulatory system ParR-ParS, Antimicrob Agents Chemother, 54, 3372, 10.1128/AAC.00242-10 MacLeod, 2000, Aminoglycoside-resistance mechanisms for cystic fibrosis Pseudomonas aeruginosa isolates are unchanged by long-term, intermittent, inhaled tobramycin treatment, J Infect Dis, 181, 1180, 10.1086/315312 Hentzer, 2001, Alginate overproduction affects Pseudomonas aeruginosa biofilm structure and function, J Bacteriol, 183, 5395, 10.1128/JB.183.18.5395-5401.2001 Cookson, 2018, New opportunities for managing acute and chronic lung infections, Nat Rev Microbiol, 16, 111, 10.1038/nrmicro.2017.122 Mahenthiralingam, 2014, Emerging cystic fibrosis pathogens and the microbiome, Paediatr Respir Rev, 15, 13 Bittar, 2010, Detection and accurate identification of new or emerging bacteria in cystic fibrosis patients, Clin Microbiol Infect, 16, 809, 10.1111/j.1469-0691.2010.03236.x Ma, 2022, Regulation of biofilm exopolysaccharide biosynthesis and degradation in Pseudomonas aeruginosa, Annu Rev Microbiol, 76, 10.1146/annurev-micro-041320-111355 Hoiby, 2010, Pseudomonas aeruginosa biofilms in cystic fibrosis, Future Microbiol, 5, 1663, 10.2217/fmb.10.125 Doggett, 1969, Incidence of mucoid Pseudomonas aeruginosa from clinical sources, Appl Microbiol, 18, 936, 10.1128/am.18.5.936-937.1969 Linker, 1964, A polysaccharide resembling alginic acid from a Pseudomonas micro-organism, Nature, 204, 187, 10.1038/204187a0 Evans, 1973, Production and characterization of the slime polysaccharide of Pseudomonas aeruginosa, J Bacteriol, 116, 915, 10.1128/jb.116.2.915-924.1973 May, 1991, Alginate synthesis by Pseudomonas aeruginosa: a key pathogenic factor in chronic pulmonary infections of cystic fibrosis patients, Clin Microbiol Rev, 4, 191, 10.1128/CMR.4.2.191 Lee, 2005, Heterogeneity of biofilms formed by nonmucoid Pseudomonas aeruginosa isolates from patients with cystic fibrosis, J Clin Microbiol, 43, 5247, 10.1128/JCM.43.10.5247-5255.2005 Guo, 2020, Structures, properties and application of alginic acid: a review, Int J Biol Macromol, 162, 618, 10.1016/j.ijbiomac.2020.06.180 Massip-Copiz, 2018, Extracellular pH and lung infections in cystic fibrosis, Eur J Cell Biol, 97, 402, 10.1016/j.ejcb.2018.06.001 Ojoo, 2005, Exhaled breath condensate pH and exhaled nitric oxide in allergic asthma and in cystic fibrosis, Thorax, 60, 22, 10.1136/thx.2003.017327 Braccini, 1999, Conformational and configurational features of acidic polysaccharides and their interactions with calcium ions: a molecular modeling investigation, Carbohydr Res, 317, 119, 10.1016/S0008-6215(99)00062-2 Smith, 2014, Elevated metal concentrations in the CF airway correlate with cellular injury and disease severity, J Cyst Fibros, 13, 289, 10.1016/j.jcf.2013.12.001 Lam, 1980, Production of mucoid microcolonies by Pseudomonas aeruginosa within infected lungs in cystic fibrosis, Infect Immun, 28, 546, 10.1128/iai.28.2.546-556.1980 Gordon, 1988, Antibiotic interaction and diffusion through alginate and exopolysaccharide of cystic fibrosis-derived Pseudomonas aeruginosa, J Antimicrob Chemother, 22, 667, 10.1093/jac/22.5.667 Nichols, 1988, Inhibition of tobramycin diffusion by binding to alginate, Antimicrob Agents Chemother, 32, 518, 10.1128/AAC.32.4.518 lannuccelli, 1996, Biodegradable intraoperative system for bone infection treatment. I. The drug/polymer interaction, Int J Pharm, 143, 195, 10.1016/S0378-5173(96)04703-5 Heriot, 2019, Interaction of gentamicin sulfate with alginate and consequences on the physico-chemical properties of alginate-containing biofilms, Int J Biol Macromol, 121, 390, 10.1016/j.ijbiomac.2018.10.025 Song, 2014, Stiffness of cross-linked poly(dimethylsiloxane) affects bacterial adhesion and antibiotic susceptibility of attached cells, Langmuir, 30, 10354, 10.1021/la502029f Chanasit, 2020, Analysis of the alginate O-acetylation machinery in Pseudomonas aeruginosa, Appl Microbiol Biotechnol, 104, 2179, 10.1007/s00253-019-10310-6 Mayer, 1999, The role of intermolecular interactions: studies on model systems for bacterial biofilms, Int J Biol Macromol, 26, 3, 10.1016/S0141-8130(99)00057-4 DiRita, 2001, Role of alginate O acetylation in resistance of mucoid Pseudomonas aeruginosa to opsonic phagocytosis, Infect Immun, 69, 1895, 10.1128/IAI.69.3.1895-1901.2001 Ertesvåg, 2015, Alginate-modifying enzymes: biological roles and biotechnological uses, Front Microbiol, 6 Lamppa, 2013, Alginate lyase exhibits catalysis-independent biofilm dispersion and antibiotic synergy, Antimicrob Agents Chemother, 57, 137, 10.1128/AAC.01789-12 Skjåk-Bræk, 1989, Effect of acetylation on some solution and gelling properties of alginates, Carbohydr Res, 185, 131, 10.1016/0008-6215(89)84028-5 Boucher, 2007, Evidence for airway surface dehydration as the initiating event in CF airway disease, J Intern Med, 261, 5, 10.1111/j.1365-2796.2006.01744.x Schnider-Keel, 2001, The sigma factor AlgU (AlgT) controls exopolysaccharide production and tolerance towards desiccation and osmotic stress in the biocontrol agent Pseudomonas fluorescens CHA0, Appl Environ Microbiol, 67, 5683, 10.1128/AEM.67.12.5683-5693.2001 DeVault, 1990, Pulmonary dehydration and infection in cystic fibrosis: evidence that ethanol activates alginate gene expression and induction of mucoidy in Pseudomonas aeruginosa, Mol Microbiol, 4, 737, 10.1111/j.1365-2958.1990.tb00644.x Tashiro, 2014, Low concentrations of ethanol stimulate biofilm and pellicle formation in Pseudomonas aeruginosa, Biosci Biotechnol Biochem, 78, 178, 10.1080/09168451.2014.877828 Ibáñez de Aldecoa, 2017, Mechanisms and regulation of extracellular DNA release and its biological roles in microbial communities, Front Microbiol, 8, 10.3389/fmicb.2017.01390 Potter, 1969, Studies on pulmonary secretions. 3. The nucleic acids in whole pulmonary secretions from patients with cystic fibrosis, bronchiectasis, and laryngectomy, Am Rev Respir Dis, 99, 909 Shah, 1996, In vivo effects of recombinant human DNase I on sputum in patients with cystic fibrosis, Thorax, 51, 119, 10.1136/thx.51.2.119 Picot, 1978, Pus, deoxyribonucleic acid, and sputum viscosity, Thorax, 33, 235, 10.1136/thx.33.2.235 Mulcahy, 2008, Extracellular DNA chelates cations and induces antibiotic resistance in Pseudomonas aeruginosa biofilms, PLoS Pathog, 4, 10.1371/journal.ppat.1000213 Egli, 2002, DNA-cation interactions: quo vadis?, Chem Biol, 9, 277, 10.1016/S1074-5521(02)00116-3 Dobi, 1998, Submillimolar levels of calcium regulates DNA structure at the dinucleotide repeat (TG/AC)n, Proc Natl Acad Sci U S A, 95, 5981, 10.1073/pnas.95.11.5981 Powell, 2018, Targeted disruption of the extracellular polymeric network of Pseudomonas aeruginosa biofilms by alginate oligosaccharides, NPJ Biofilms Microbiomes, 4, 13, 10.1038/s41522-018-0056-3 Turnbull, 2016, Explosive cell lysis as a mechanism for the biogenesis of bacterial membrane vesicles and biofilms, Nat Commun, 7, 10.1038/ncomms11220 Alhede, 2020, The origin of extracellular DNA in bacterial biofilm infections in vivo, Pathog Dis, 78, 10.1093/femspd/ftaa018 Chiang, 2013, Extracellular DNA shields against aminoglycosides in Pseudomonas aeruginosa biofilms, Antimicrob Agents Chemother, 57, 2352, 10.1128/AAC.00001-13 Allesen-Holm, 2006, A characterization of DNA release in Pseudomonas aeruginosa cultures and biofilms, Mol Microbiol, 59, 1114, 10.1111/j.1365-2958.2005.05008.x Lethem, 1990, The origin of DNA associated with mucus glycoproteins in cystic fibrosis sputum, Eur Respir J, 3, 19, 10.1183/09031936.93.03010019 Martínez-Alemán, 2017, Understanding the entanglement: neutrophil extracellular traps (NETs) in cystic fibrosis, Front Cell Infect Microbiol, 7, 10.3389/fcimb.2017.00104 Whitchurch, 2002, Extracellular DNA required for bacterial biofilm formation, Science, 295, 10.1126/science.295.5559.1487 Wang, 2015, The exopolysaccharide Psl-eDNA interaction enables the formation of a biofilm skeleton in Pseudomonas aeruginosa, Environ Microbiol Rep, 7, 330, 10.1111/1758-2229.12252 Seviour, 2021, The biofilm matrix scaffold of Pseudomonas aeruginosa contains G-quadruplex extracellular DNA structures, Npj Biofilms Microbi, 7, 10.1038/s41522-021-00197-5 Dell'Anno, 2005, Extracellular DNA plays a key role in deep-sea ecosystem functioning, Science, 309, 10.1126/science.1117475 Mulcahy, 2010, Pseudomonas aeruginosa produces an extracellular deoxyribonuclease that is required for utilization of DNA as a nutrient source, Environ Microbiol, 12, 1621, 10.1111/j.1462-2920.2010.02208.x Prudhomme, 2006, Antibiotic stress induces genetic transformability in the human pathogen Streptococcus pneumoniae, Science, 313, 89, 10.1126/science.1127912 Rajendran, 2013, Extracellular DNA release acts as an antifungal resistance mechanism in mature Aspergillus fumigatus biofilms, Eukaryot Cell, 12, 420, 10.1128/EC.00287-12 Freschi, 2018, The Pseudomonas aeruginosa pan-genome provides new insights on its population structure, horizontal gene transfer, and pathogenicity, Genome Biology and Evolution, 11, 109, 10.1093/gbe/evy259 Qiu, 2009, Role of horizontal gene transfer in the evolution of Pseudomonas aeruginosa virulence, Genome Dyn, 6, 126, 10.1159/000235767 Wilton, 2016, Extracellular DNA acidifies biofilms and induces aminoglycoside resistance in Pseudomonas aeruginosa, Antimicrob Agents Chemother, 60, 544, 10.1128/AAC.01650-15 Friedman, 2004, Genes involved in matrix formation in Pseudomonas aeruginosa PA14 biofilms, Mol Microbiol, 51, 675, 10.1046/j.1365-2958.2003.03877.x Jennings, 2015, Pel is a cationic exopolysaccharide that cross-links extracellular DNA in the Pseudomonas aeruginosa biofilm matrix, Proc Natl Acad Sci USA, 112, 11353, 10.1073/pnas.1503058112 Häussler, 2009, New perspectives at the heart of surface-associated microbial communities, J Bacteriol, 192, 2941, 10.1128/JB.00332-10 Colvin, 2011, The pel polysaccharide can serve a structural and protective role in the biofilm matrix of Pseudomonas aeruginosa, PLoS Pathog, 7, 10.1371/journal.ppat.1001264 Madsen, 2015, Facultative control of matrix production optimizes competitive fitness in Pseudomonas aeruginosa PA14 biofilm models, Appl Environ Microbiol, 81, 8414, 10.1128/AEM.02628-15 Yoon, 2002, Pseudomonas aeruginosa anaerobic respiration in biofilms: relationships to cystic fibrosis pathogenesis, Dev Cell, 3, 593, 10.1016/S1534-5807(02)00295-2 Montgomery, 2017, Hypoxia and sterile inflammation in cystic fibrosis airways: mechanisms and potential therapies, Eur Respir J, 49, 10.1183/13993003.00903-2016 Borriello, 2004, Oxygen limitation contributes to antibiotic tolerance of Pseudomonas aeruginosa in biofilms, Antimicrob Agents Chemother, 48, 2659, 10.1128/AAC.48.7.2659-2664.2004 Khan, 2010, Aminoglycoside resistance of Pseudomonas aeruginosa biofilms modulated by extracellular polysaccharide, Int Microbiol, 13, 207 Friedman, 2004, Two genetic loci produce distinct carbohydrate-rich structural components of the Pseudomonas aeruginosa biofilm matrix, J Bacteriol, 186, 4457, 10.1128/JB.186.14.4457-4465.2004 Ma, 2007, Pseudomonas aeruginosa Psl is a galactose- and mannose-rich exopolysaccharide, J Bacteriol, 189, 8353, 10.1128/JB.00620-07 Byrd, 2009, Genetic and biochemical analyses of the Pseudomonas aeruginosa Psl exopolysaccharide reveal overlapping roles for polysaccharide synthesis enzymes in Psl and LPS production, Mol Microbiol, 73, 622, 10.1111/j.1365-2958.2009.06795.x Ma, 2012, Synthesis of multiple Pseudomonas aeruginosa biofilm matrix exopolysaccharides is post-transcriptionally regulated, Environ Microbiol, 14, 1995, 10.1111/j.1462-2920.2012.02753.x Colvin, 2012, The Pel and Psl polysaccharides provide Pseudomonas aeruginosa structural redundancy within the biofilm matrix, Environ Microbiol, 14, 1913, 10.1111/j.1462-2920.2011.02657.x Kovach, 2017, Evolutionary adaptations of biofilms infecting cystic fibrosis lungs promote mechanical toughness by adjusting polysaccharide production, Npj Biofilms Microbi, 3, 1, 10.1038/s41522-016-0007-9 Ma, 2009, Assembly and development of the Pseudomonas aeruginosa biofilm matrix, PLoS Pathog, 5, 10.1371/journal.ppat.1000354 Mishra, 2012, Pseudomonas aeruginosa Psl polysaccharide reduces neutrophil phagocytosis and the oxidative response by limiting complement-mediated opsonization, Cell Microbiol, 14, 95, 10.1111/j.1462-5822.2011.01704.x Jones, 2017, Psl produced by mucoid Pseudomonas aeruginosa contributes to the establishment of biofilms and immune evasion, mBio, 8, 10.1128/mBio.00864-17 Borlee, 2010, Pseudomonas aeruginosa uses a cyclic-di-GMP-regulated adhesin to reinforce the biofilm extracellular matrix, Mol Microbiol, 75, 827, 10.1111/j.1365-2958.2009.06991.x Reichhardt, 2018, CdrA interactions within the Pseudomonas aeruginosa biofilm matrix safeguard it from proteolysis and promote cellular packing, mBio, 9, 10.1128/mBio.01376-18 Passos da Silva, 2019, The Pseudomonas aeruginosa lectin LecB binds to the exopolysaccharide Psl and stabilizes the biofilm matrix, Nat Commun, 10, 2183, 10.1038/s41467-019-10201-4 Geddes-McAlister, 2019, Tasked with a challenging objective: why do neutrophils fail to battle Pseudomonas aeruginosa biofilms, Pathogens, 8, 283, 10.3390/pathogens8040283 Govan, 1996, Microbial pathogenesis in cystic fibrosis: mucoid Pseudomonas aeruginosa and Burkholderia cepacia, Microbiol Rev, 60, 539, 10.1128/mr.60.3.539-574.1996 Billings, 2013, The extracellular matrix component psl provides fast-acting antibiotic defense in Pseudomonas aeruginosa biofilms, PLoS Pathog, 9, 10.1371/journal.ppat.1003526 Hansson, 2019, Mucus and mucins in diseases of the intestinal and respiratory tracts, J Intern Med, 285, 479, 10.1111/joim.12910 Bromberg, 1999, Aggregation phenomena in aqueous solutions of hydrophobically modified polyelectrolytes, A Probe Solubilization Study, Macromolecules, 32, 3649, 10.1021/ma981946k Raynal, 2002, Concentrated solutions of salivary MUC5B mucin do not replicate the gel-forming properties of saliva, Biochem J, 362 Pt 2, 289, 10.1042/bj3620289 Schipper, 2007, Saliva as research material: biochemical, physicochemical and practical aspects, Arch Oral Biol, 52, 1114, 10.1016/j.archoralbio.2007.06.009 Petrou, 2018, Mucins as multifunctional building blocks of biomaterials, Biomater Sci, 6, 2282, 10.1039/C8BM00471D Mitri, 2020, Novel anti-inflammatory approaches for cystic fibrosis lung disease: identification of molecular targets and design of innovative therapies, Front Pharmacol, 11, 1096, 10.3389/fphar.2020.01096 Song, 2003, Interleukin-1β and tumor necrosis factor-α induce MUC5AC overexpression through a mechanism involving ERK/p38 mitogen-activated protein kinases-MSK1-CREB activation in human airway epithelial cells, J Biol Chem, 278, 23243, 10.1074/jbc.M300096200 Yeung, 2012, Mucin promotes rapid surface motility in Pseudomonas aeruginosa, mBio, 3, 10.1128/mBio.00073-12 Landry, 2006, Mucin-Pseudomonas aeruginosa interactions promote biofilm formation and antibiotic resistance, Mol Microbiol, 59, 142, 10.1111/j.1365-2958.2005.04941.x Haley, 2012, Characterization of biofilm-like structures formed by Pseudomonas aeruginosa in a synthetic mucus medium, BMC Microbiol, 12, 10.1186/1471-2180-12-181 Co, 2018, Mucins trigger dispersal of Pseudomonas aeruginosa biofilms, Npj Biofilms Microbi, 4, 23, 10.1038/s41522-018-0067-0 Van den Bossche, 2021, The cystic fibrosis lung microenvironment alters antibiotic activity: causes and effects, Eur Respir Rev, 30, 10.1183/16000617.0055-2021 Baos, 2012, Distribution of sialic acids on mucins and gels: a defense mechanism, Biophys J, 102, 176, 10.1016/j.bpj.2011.08.058 Kim, 2020, N-glycan modifications with negative charge in a natural polymer mucin from bovine submaxillary glands, and their structural role, Polymers (Basel), 13, 10.3390/polym13010103 Huang, 2015, Mucin binding reduces colistin antimicrobial activity, Antimicrob Agents Chemother, 59, 5925, 10.1128/AAC.00808-15 Samad, 2019, Mucus and mucin environments reduce the efficacy of polymyxin and fluoroquinolone antibiotics against Pseudomonas aeruginosa, ACS Biomater Sci Eng, 5, 1189, 10.1021/acsbiomaterials.8b01054 Grainger, 2006, Culture of calu-3 cells at the air interface provides a representative model of the airway epithelial barrier, Pharmaceut Res, 23, 1482, 10.1007/s11095-006-0255-0 Lock, 2018, Mucus models to evaluate the diffusion of drugs and particles, Adv Drug Deliv Rev, 124, 34, 10.1016/j.addr.2017.11.001 Pacheco, 2019, Disassembling the complexity of mucus barriers to develop a fast screening tool for early drug discovery, J Mater Chem B, 7, 4940, 10.1039/C9TB00957D Bhat, 1996, Drug diffusion through cystic fibrotic mucus: steady-state permeation, rheologic properties, and glycoprotein morphology, J Pharmacol Sci, 85, 624, 10.1021/js950381s Butnarasu, 2022, Cystic fibrosis mucus model to design more efficient drug therapies, Mol Pharm, 19, 520, 10.1021/acs.molpharmaceut.1c00644 Petri, 2003, Absorption/metabolism of sulforaphane and quercetin, and regulation of phase II enzymes, in human jejunum in vivo, Drug Metab Dispos, 31, 805, 10.1124/dmd.31.6.805 Bhattacharjee, 2017, Nanoparticle passage through porcine jejunal mucus: microfluidics and rheology, Nanomed Nanotechnol Biol Med, 13, 863, 10.1016/j.nano.2016.11.017 Boegh, 2014, Property profiling of biosimilar mucus in a novel mucus-containing in vitro model for assessment of intestinal drug absorption, Eur J Pharm Biopharm, 87, 227, 10.1016/j.ejpb.2014.01.001 Falavigna, 2018, Mucus-PVPA (mucus Phospholipid Vesicle-based Permeation Assay): an artificial permeability tool for drug screening and formulation development, Int J Pharm, 537, 213, 10.1016/j.ijpharm.2017.12.038 Wang, 2021, Mucin glycans signal through the sensor kinase RetS to inhibit virulence-associated traits in Pseudomonas aeruginosa, Curr Biol, 31, 90, 10.1016/j.cub.2020.09.088 Morrison, 2019, Mucus, mucins, and cystic fibrosis, Pediatr Pulmonol, 54, S84 Korgaonkar, 2013, Community surveillance enhances Pseudomonas aeruginosa virulence during polymicrobial infection, Proc Natl Acad Sci U S A, 110, 1059, 10.1073/pnas.1214550110 Wheeler, 2019, Mucin glycans attenuate the virulence of Pseudomonas aeruginosa in infection, Nat Microbiol, 4, 2146, 10.1038/s41564-019-0581-8 Hoffman, 2020, Host mucin is exploited by Pseudomonas aeruginosa to provide monosaccharides required for a successful infection, mBio, 11, 10.1128/mBio.00060-20 Tang, 2016, Acidic pH increases airway surface liquid viscosity in cystic fibrosis, J Clin Invest, 126, 879, 10.1172/JCI83922 Smith, 2013, Targeting iron uptake to control Pseudomonas aeruginosa infections in cystic fibrosis, Eur Respir J, 42, 1723, 10.1183/09031936.00124012 Tyrrell, 2016, Iron acquisition in the cystic fibrosis lung and potential for novel therapeutic strategies, Microbiology, 162, 191, 10.1099/mic.0.000220 Dieppois, 2012, The transcriptional regulator CzcR modulates antibiotic resistance and quorum sensing in Pseudomonas aeruginosa, PLoS One, 7, 10.1371/journal.pone.0038148 Bremer, 2019, Responses of microorganisms to osmotic stress, Annu Rev Microbiol, 73, 313, 10.1146/annurev-micro-020518-115504 Aspedon, 2006, Microarray analysis of the osmotic stress response in Pseudomonas aeruginosa, J Bacteriol, 188, 2721, 10.1128/JB.188.7.2721-2725.2006 Price-Whelan, 2006, Rethinking 'secondary' metabolism: physiological roles for phenazine antibiotics, Nat Chem Biol, 2, 71, 10.1038/nchembio764 Mavrodi, 2001, Functional analysis of genes for biosynthesis of pyocyanin and phenazine-1-carboxamide from Pseudomonas aeruginosa PAO1, J Bacteriol, 183, 6454, 10.1128/JB.183.21.6454-6465.2001 Lauredo, 1998, Mechanism of pyocyanin- and 1-hydroxyphenazine-induced lung neutrophilia in sheep airways, J Appl Physiol, 85, 2298, 10.1152/jappl.1998.85.6.2298 Lau, 2004, Pseudomonas aeruginosa pyocyanin is critical for lung infection in mice, Infect Immun, 72, 4275, 10.1128/IAI.72.7.4275-4278.2004 Das, 2015, Phenazine virulence factor binding to extracellular DNA is important for Pseudomonas aeruginosa biofilm formation, Sci Rep-Uk, 5, 8398, 10.1038/srep08398 Mah, 2003, A genetic basis for Pseudomonas aeruginosa biofilm antibiotic resistance, Nature, 426, 306, 10.1038/nature02122 Sadovskaya, 2010, High-level antibiotic resistance in Pseudomonas aeruginosa biofilm: the ndvB gene is involved in the production of highly glycerol-phosphorylated β-(1→3)-glucans, which bind aminoglycosides, Glycobiology, 20, 895, 10.1093/glycob/cwq047 Scoffone, 2019, Quorum sensing as antivirulence target in cystic fibrosis pathogens, Int J Mol Sci, 20, 1838, 10.3390/ijms20081838 Balasubramanian, 2012, A dynamic and intricate regulatory network determines Pseudomonas aeruginosa virulence, Nucleic Acids Res, 41, 1, 10.1093/nar/gks1039 Briaud, 2020, Impact of coexistence phenotype between Staphylococcus aureus and Pseudomonas aeruginosa isolates on clinical outcomes among cystic fibrosis patients, Front Cell Infect Microbiol, 10, 266, 10.3389/fcimb.2020.00266 Camus, 2021, How bacterial adaptation to cystic fibrosis environment shapes interactions between Pseudomonas aeruginosa and Staphylococcus aureus, Front Microbiol, 12, 10.3389/fmicb.2021.617784 Hotterbeekx, 2017, In vivo and in vitro Interactions between Pseudomonas aeruginosa and Staphylococcus spp, Front Cell Infect Microbiol, 7, 106, 10.3389/fcimb.2017.00106