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The Yin and Yang of Phenazine Physiology

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Book cover Microbial Phenazines

Abstract

Microorganisms are seldom solitary. They are surrounded by both clonal cells and other members of the local microbial community, and they often exist in, on, or in close proximity to multi-cellular host organisms like plants and humans. Whether in vivo during infection or in situ in the nutrient rich rhizosphere, microorganisms affect each other and the host. Phenazines, a class of secondary metabolites secreted by diverse bacteria, are best known for their antibiotic properties and have been shown to affect a broad spectrum of organisms ranging from bacteria over fungi, plants, nematodes, parasites, and humans. However, phenazines are also involved in numerous aspects of bacterial physiology like survival, iron acquisition, signaling, and biofilm formation in ways that have the potential to increase the fitness of both the phenazine-producing strain and non-producers alike. The overarching theme of this chapter is that phenazines can be beneficial or detrimental to organisms, depending on the milieu and one's perspective. In this chapter, we will highlight specific examples to discuss the yin and yang of phenazine physiology.

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References

  • Allen L, Dockrell DH, Pattery T et al (2005) Pyocyanin production by Pseudomonas aeruginosa induces neutrophil apoptosis and impairs neutrophil-mediated host defenses in vivo. J Immunol 174(6):3643–3649

    PubMed  CAS  Google Scholar 

  • Alves MJ, Rabinovitch M (1983) Destruction of intracellular Trypanosoma cruzi after treatment of infected macrophages with cationic electron carriers. Infect Immun 39(1):435–438

    PubMed  CAS  Google Scholar 

  • Amin R, Dupuis A, Aaron SD et al (2010) The effect of chronic infection with Aspergillus fumigatus on lung function and hospitalization in patients with cystic fibrosis. Chest 137(1):171–176

    PubMed  Google Scholar 

  • Aoki S, Ito-Kuwa S (1982) Respiration of Candida albicans in relation to its morphogenesis. Plant Cell Physiol 23(4):721–726

    Google Scholar 

  • Armstrong AV, Stewart-Tull DE (1971) The site of the activity of extracellular products of Pseudomonas aeruginosa in the electron-transport chain in mammalian cell respiration. J Med Microbiol 4(2):263–270

    PubMed  CAS  Google Scholar 

  • Armstrong AV, Stewart-Tull DE, Roberts JS (1971) Characterisation of the Pseudomonas aeruginosa factor that inhibits mouse-liver mitochondrial respiration. J Med Microbiol 4(2):249–262

    PubMed  CAS  Google Scholar 

  • Audenaert K, Pattery T, Cornelis P et al (2002) Induction of systemic resistance to Botyris cinerea in tomato by Pseudomonas aeruginosa 7NSK2: role of salicylic acid, pyocholin, and pyocyanin. Mol Plant Microbe Interact 15:1147–1156

    PubMed  CAS  Google Scholar 

  • Avital A, Uwyyed K, Picard E et al (1995) Sensitivity and specificity of oropharyngeal suction versus bronchoalveolar lavage in identifying respiratory tract pathogens in children with chronic pulmonary infection. Pediatr Pulmonol 20(1):40–43

    PubMed  CAS  Google Scholar 

  • Banin E, Lozinski A, Brady KM et al (2008) The potential of desferrioxamine-gallium as an anti-Pseudomonas therapeutic agent. Proc Natl Acad Sci USA 105(43):16761–16766

    PubMed  CAS  Google Scholar 

  • Baron SS, Rowe JJ (1981) Antibiotic action of pyocyanin. Antimicrob Agents Chemother 20(6):814–820

    PubMed  CAS  Google Scholar 

  • Baron SS, Terranova G, Rowe JJ (1989) Molecular mechanism of the antimicrobial action of pyocyanin. Curr Microbiol 18:223–230

    CAS  Google Scholar 

  • Barron ES, Hoffman LA (1930) The catalytic effect of dyes on the oxygen consumption of living cells. J Gen Physiol 13(4):483–494

    PubMed  CAS  Google Scholar 

  • Bauernfeind A, Hörl G, Jungwirth R et al (1987) Qualitative and quantitative microbiological analysis of sputa of 102 patients with cystic fibrosis. Infection 15(4):270–277

    PubMed  CAS  Google Scholar 

  • Bhargava V, Tomashefski JF Jr, Stern RC et al (1989) The pathology of fungal infection and colonization in patients with cystic fibrosis. Hum Pathol 20(10):977–986

    PubMed  CAS  Google Scholar 

  • Bolwerk A, Lagopodi AL, Wijfjes AH et al (2003) Interactions in the tomato rhizosphere of two Pseudomonas biocontrol strains with the phytopathogenic fungus Fusarium oxysporum f. sp. radicis-lycopersici. Mol Plant Microbe Interact 16(11):983–993

    PubMed  CAS  Google Scholar 

  • Brisbane PG, Janik L, Tate M et al (1987) Revised structure for the phenazine antibiotic from Pseudomonas fluorescens 2-79 (NRRL B-15132). Antimicrob Agents Chemother 31(12):1967–1971

    PubMed  CAS  Google Scholar 

  • Bull CT, Weller DM, Thomashow LS (1991) Relationship between root colonization and suppression of Gaeumannomyces graminis var. tritici by Pseudomonas fluorescens strain 2-79. Phytopathology 81:954–959

    Google Scholar 

  • Burns JL, Van Dalfsen JM, Shawar RM et al (1999) Effect of chronic intermittent administration of inhaled tobramycin on respiratory microbial flora in patients with cystic fibrosis. J Infect Dis 179(5):1190–1196

    PubMed  CAS  Google Scholar 

  • Byng GS, Eustice DC, Jensen RA (1963) Biosynthesis of phenazine pigments in mutant and wild-type cultures of Pseudomonas aeruginosa. J Bacteriol 138:846–852

    Google Scholar 

  • Cezairliyan B, Vinayavekhin N, Grenfell-Lee D et al (2013) Identification of Pseudomonas aeruginosa phenazines that kill Caenorhabditis elegans. PLoS Pathog 9(1):e1003101

    PubMed  CAS  Google Scholar 

  • Chang HR, Pechere JC (1989) In-vitro toxoplasmacidal activity of cationic electron carriers. J Antimicrob Chemother 23(2):229–235

    PubMed  CAS  Google Scholar 

  • Chin-A-Woeng, TF, Bloemberg GV, van der Bij AJ et al (1998) Biocontrol by phenazine-1-carboxamide-producing Pseudomonas chlororaphis PCL1391 of tomato root rot caused by Fusarium oxysporum f. sp. radicis-lycopersici. Mol Plant Microbe Interact 11(11):1069–1077

    Google Scholar 

  • Chin-A-Woeng TF, Bloemberg GV, Mulders IH, Dekkers LC, Lugtenberg BJ (2000) Root colonization by phenazine-1-carboxamide-producing bacterium Pseudomonas chlororaphis PCL1391 is essential for biocontrol of tomato foot and root rot. Mol Plant Microbe Interact 13: 1340–1345

    Google Scholar 

  • Chotirmall SH, O’Donoghue E, Bennett K et al (2010) Sputum Candida albicans presages FEV(1) decline and hospital-treated exacerbations in cystic fibrosis. Chest 138(5):1186–1195

    PubMed  Google Scholar 

  • Cornelis P, Matthijs S (2002) Diversity of siderophore-mediated iron uptake systems in fluorescent pseudomonads: not only pyoverdines. Environ Microbiol 4(12):787–798

    PubMed  CAS  Google Scholar 

  • Cox CD (1980) Iron reductases from Pseudomonas aeruginosa. J Bacteriol 141(1):199–204

    PubMed  CAS  Google Scholar 

  • Cox CD (1986) Role of pyocyanin in the acquisition of iron from transferrin. Infect Immun 52(1):263–270

    PubMed  CAS  Google Scholar 

  • Cugini C, Calfee MW, Farrow JM et al (2007) Farnesol, a common sesquiterpene, inhibits PQS production in Pseudomonas aeruginosa. Mol Microbiol 65(4):896–906

    PubMed  CAS  Google Scholar 

  • Cugini C, Morales DK, Hogan DA (2010) Candida albicans-produced farnesol stimulates Pseudomonas quinolone signal production in LasR-defective Pseudomonas aeruginosa strains. Microbiology 156(10):3096–3107

    Google Scholar 

  • de Andrade-Neto VF, Goulart MOF, da Silva Filho JF et al (2004) Antimalarial activity of phenazines from lapachol, beta-lapachone and its derivatives against Plasmodium falciparum in vitro and Plasmodium berghei in vivo. Bioorg Med Chem Lett 14(5):1145–1149

    PubMed  Google Scholar 

  • de Macedo JL, Santos JB (2005) Bacterial and fungal colonization of burn wounds. Mem Inst Oswaldo Cruz 100(5):535–539

    PubMed  Google Scholar 

  • De Vleesschauwer D, Cornelis P, Höfte M (2006) Redox-active pyocyanin secreted by Pseudomonas aeruginosa 7NSK2 triggers systemic resistance to Magnaporthe grisea but enhances Rhizoctonia solani susceptibility in rice. Mol Plant Microbe Interact 19(12):1406–1419

    Google Scholar 

  • Denning GM, Wollenweber LA, Railsback MA et al (1998a) Pseudomonas pyocyanin increases interleukin-8 expression by human airway epithelial cells. Infect Immun 66(12):5777–5784

    PubMed  CAS  Google Scholar 

  • Denning GM, Railsback MA, Rasmussen GT et al (1998b) Pseudomonas pyocyanine alters calcium signaling in human airway epithelial cells. Am J Physiol 274(6 Pt 1):L893–L900

    PubMed  CAS  Google Scholar 

  • Dietrich LE, Price-Whelan A, Petersen A et al (2006) The phenazine pyocyanin is a terminal signaling factor in the quorum sensing network of Pseudomonas aeruginosa. Mol Microbiol 61(5):1308–1321

    PubMed  CAS  Google Scholar 

  • Dietrich LEP, Price-Whelan A, Teal T et al (2008) Redox-active antibiotics control gene expression and community behavior in divergent bacteria. Science 321:1203–1206

    PubMed  CAS  Google Scholar 

  • Dietrich LE, Okegbe C, Price-Whelan A et al (2013) Bacterial community morphogenesis is intimately linked to the intracellular redox state. J Bacteriol 195(7):1371–1380

    PubMed  CAS  Google Scholar 

  • Dong YH, Zhang XF, An SW et al (2008) A novel two-component system BqsS-BqsR modulates quorum sensing-dependent biofilm decay in Pseudomonas aeruginosa. Commun Integr Biol 1(1):88–96

    PubMed  CAS  Google Scholar 

  • Dwivedi D, Johri BN, Ineichen K et al (2009) Impact of antifungals producing rhizobacteria on the performance of Vigna radiata in the presence of arbuscular mycorrhizal fungi. Mycorrhiza 19(8):559–570

    PubMed  CAS  Google Scholar 

  • Emde R, Schink B (1990) Oxidation of glycerol, lactate, and propionate by Propionibacterium freudenreichii in a poised-potential amperometric culture system. Arch Microbiol 153(5):506–512

    CAS  Google Scholar 

  • Emde R, Swain A, Schink B (1989) Anaerobic oxidation of glycerol by Escherichia coli in an amperometric poised-potential culture system. Appl Microbiol Biotechnol 32:170–175

    CAS  Google Scholar 

  • Emmerich R, Löw O (1899) Bakteriolytische Enzyme als Ursache der erworbenen Immunität und die Heilung von Infectionskrankheiten durch dieselben. Z. Hygiene Infektionskrankheiten 31(1):1–65

    Google Scholar 

  • Eschbach M, Schreiber K, Trunk K et al (2004) Long-term anaerobic survival of the opportunistic pathogen Pseudomonas aeruginosa via pyruvate fermentation. J Bacteriol 186(14):4596–4604

    PubMed  CAS  Google Scholar 

  • Fitzpatrick DA (2009) Lines of evidence for horizontal gene transfer of a phenazine producing operon into multiple bacterial species. J Mol Evol 68(2):171–185

    PubMed  CAS  Google Scholar 

  • French SW, Palmer DS, Sim WA (1973) Phenazine methosulfate uptake by rat liver mitochondria. Can J Biochem 51(3):235–240

    PubMed  CAS  Google Scholar 

  • Friedheim EA (1931) Pyocyanine, an accessory respiratory enzyme. J Exp Med 54(2):207–221

    PubMed  CAS  Google Scholar 

  • Friedheim EA (1934) The effect of pyocyanine on the respiration of some normal tissues and tumours. Biochem J 28(1):173–179

    PubMed  CAS  Google Scholar 

  • Gibson J, Sood A, Hogan DA (2009) Pseudomonas aeruginosa-Candida albicans interactions: localization and fungal toxicity of a phenazine derivative. Appl Environ Microbiol 75(2):504–513

    PubMed  CAS  Google Scholar 

  • Giddens SR, Houliston GJ, Mahanty HK (2003) The influence of antibiotic production and pre-emptive colonization on the population dynamics of Pantoea agglomerans (Erwinia herbicola) Eh1087 and Erwinia amylovora in planta. Environ Microbiol 5(10):1016–1021

    PubMed  CAS  Google Scholar 

  • Glasser NR, Kern SE, Newman DK. Phenazine redox cycling enhances anaerobic survival in Pseudomonas aeruginosa by promoting fermentation and ATP synthesis. Submitted

    Google Scholar 

  • Gohain N, Thomashow LS, Mavrodi DV et al (2006) The purification, crystallization and preliminary structural characterization of FAD-dependent monooxygenase PhzS, a phenazine-modifying enzyme from Pseudomonas aeruginosa. Acta Crystallogr, Sect F: Struct Biol Cryst Commun 62(10):989–992

    CAS  Google Scholar 

  • Gu M, Imlay JA (2011) The SoxRS response of Escherichia coli is directly activated by redox-cycling drugs rather than by superoxide. Mol Microbiol 79(5):1136–1150

    PubMed  CAS  Google Scholar 

  • Gupta N, Haque A, Mukhopadhyay G et al (2005) Interactions between bacteria and Candida in the burn wound. Burns 31(3):375–378

    PubMed  Google Scholar 

  • Gurusiddaiah S, Weller DM, Sarkar A et al (1986) Characterization of an antibiotic produced by a strain of Pseudomonas fluorescens inhibitory to Gaeumannomyces graminis var. tritici and Pythium spp. Antimicrob Agents Chemother 29(3):488–495

    PubMed  CAS  Google Scholar 

  • Harmsen M, Yang L, Pamp SJ et al (2010) An update on Pseudomonas aeruginosa biofilm formation, tolerance, and dispersal. FEMS Immunol Med Microbiol 59(3):253–268

    PubMed  CAS  Google Scholar 

  • Harrison F, Paul J, Massey RC et al (2008) Interspecific competition and siderophore-mediated cooperation in Pseudomonas aeruginosa. ISME J 2(1):49–55

    PubMed  Google Scholar 

  • Harrop GA, Barron ES (1928) Studies on blood cell metabolism: I. The effect of methylene blue and other dyes upon the oxygen consumption of mammalian and avian erythrocytes. J Exp Med 48(2):207–223

    PubMed  CAS  Google Scholar 

  • Hassan HM, Fridovich I (1980) Mechanism of the antibiotic action pyocyanine. J Bacteriol 141(1):156–163

    PubMed  CAS  Google Scholar 

  • Hassett DJ, Charniga L, Bean K et al (1992) Response of Pseudomonas aeruginosa to pyocyanin: mechanisms of resistance, antioxidant defenses, and demonstration of a manganese-cofactored superoxide dismutase. Infect Immun 60(2):328–336

    PubMed  CAS  Google Scholar 

  • Hassett DJ, Schweizer HP, Ohman DE (1995) Pseudomonas aeruginosa sodA and sodB mutants defective in manganese- and iron-cofactored superoxide dismutase activity demonstrate the importance of the iron-cofactored form in aerobic metabolism. J Bacteriol 177(22):6330–6337

    PubMed  CAS  Google Scholar 

  • Hermann C, Hermann J, Munzel U et al (1999) Bacterial flora accompanying Candida yeasts in clinical specimens. Mycoses 42(11–12):619–627

    PubMed  CAS  Google Scholar 

  • Hernandez ME, Kappler A, Newman DK (2004) Phenazines and other redox-active antibiotics promote microbial mineral reduction. Appl Environ Microbiol 70(2):921–928

    PubMed  CAS  Google Scholar 

  • Hoffman LR, D’Argenio DA, MacCoss MJ et al (2010) Nutrient availability as a mechanism for selection of antibiotic tolerant Pseudomonas aeruginosa within the CF airway. PLoS Pathog 6(1):e1000712

    PubMed  Google Scholar 

  • Hogan DA, Kolter R (2002) Pseudomonas-Candida interactions: an ecological role for virulence factors. Science 296(5576):2229–2232

    PubMed  CAS  Google Scholar 

  • Hogan DA, Sundstrom P (2009) The Ras/cAMP/PKA signaling pathway and virulence in Candida albicans. Future Microbiol 4(10):1263–1270

    PubMed  CAS  Google Scholar 

  • Hollstein U, Van Gemert Jr RJ (1971) Interaction of phenazines with polydeoxyribonucleotides. Biochemistry 10(3):497–504

    PubMed  CAS  Google Scholar 

  • Huang J, Xu Y, Zhang H et al (2009) Temperature-dependent expression of phzM and its regulatory genes lasI and ptsP in rhizosphere isolate Pseudomonas sp. strain M18. Appl Environ Microbiol 75(20):6568–6580

    PubMed  CAS  Google Scholar 

  • Hughes WT, Kim HK (1973) Mycoflora in cystic fibrosis: some ecologic aspects of Pseudomonas aeruginosa and Candida albicans. Mycopathol Mycol Appl 50(3):261–269

    PubMed  CAS  Google Scholar 

  • Hunter RC, Klepac-Ceraj V, Lorenzi MM et al (2012) Phenazine content in the cystic fibrosis respiratory tract negatively correlates with lung function and microbial complexity. Am J Respir Cell Mol Biol 47:738–745

    PubMed  CAS  Google Scholar 

  • Hunter R et al (2013) Ferrous iron is a significant component of bioavailable iron in the cystic fibrosis airways. mBio 4(4):e00557–13

    Google Scholar 

  • Jackowski JT, Szepfalusi Z, Wanner DA et al (1991) Effects of P. aeruginosa-derived bacterial products on tracheal ciliary function: role of O2 radicals. Am J Physiol 260(2 Pt 1):L61–67

    Google Scholar 

  • Kahl BC, Duebbers A, Lubritz G et al (2003) Population dynamics of persistent Staphylococcus aureus isolated from the airways of cystic fibrosis patients during a 6-year prospective study. J Clin Microbiol 41(9):4424–4427

    PubMed  CAS  Google Scholar 

  • Kanner D, Gerber NN, Bartha R (1978) Pattern of phenazine pigment production by a strain of Pseudomonas aeruginosa. J Bacteriol 134(2):690–692

    PubMed  CAS  Google Scholar 

  • Kanthakumar K, Taylor G, Tsang KW et al (1993) Mechanisms of action of Pseudomonas aeruginosa pyocyanin on human ciliary beat in vitro. Infect Immun 61(7):2848–2853

    PubMed  CAS  Google Scholar 

  • Kanthakumar K, Taylor G, Tsang K et al (1996) The effect of bacterial toxins on levels of intracellular adenosine nucleotides and human ciliary beat frequency. Pulm Pharmacol 9(4):223–230

    PubMed  CAS  Google Scholar 

  • Kasozi DM, Gromer S, Adler H et al (2011) The bacterial redox signaller pyocyanin as an antiplasmodial agent: comparisons with its thioanalog methylene blue. Redox Rep 16(4):154–165

    PubMed  CAS  Google Scholar 

  • Kavitha K, Mathiyazhagan S, Sendhilvel V et al (2005) Broad spectrum action of phenazine against active and dormant structures of fungal pathogens and root knot nematode. Arch Phytopathol Plant Protect 38(1):69–76

    CAS  Google Scholar 

  • Kerr J (1994a) Inhibition of fungal growth by Pseudomonas aeruginosa and Pseudomonas cepacia isolated from patients with cystic fibrosis. J Infect 28(3):305–310

    PubMed  CAS  Google Scholar 

  • Kerr JR (1994b) Suppression of fungal growth exhibited by Pseudomonas aeruginosa. J Clin Microbiol 32(2):525–527

    PubMed  CAS  Google Scholar 

  • Kerr JR (2000) Phenazine pigments: antibiotics and virulence factors. Infect Dis Rev 2(4):184–194

    Google Scholar 

  • Kerr JR, Taylor GW, Rutman A et al (1999) Pseudomonas aeruginosa pyocyanin and 1-hydroxyphenazine inhibit fungal growth. J Clin Pathol 52(5):385–387

    PubMed  CAS  Google Scholar 

  • Khare E, Arora NK (2011) Dual activity of pyocyanin from Pseudomonas aeruginosa–antibiotic against phytopathogen and signal molecule for biofilm development by rhizobia. Can J Microbiol 57(9):708–713

    PubMed  CAS  Google Scholar 

  • Knight M, Hartman PE, Hartman Z et al (1979) A new method of preparation of pyocyanin and demonstration of an unusual bacterial sensitivity. Anal Biochem 95(1):19–23

    PubMed  CAS  Google Scholar 

  • Kong F, Young L, Chen Y et al (2006) Pseudomonas aeruginosa pyocyanin inactivates lung epithelial vacuolar ATPase-dependent cystic fibrosis transmembrane conductance regulator expression and localization. Cell Microbiol 8(7):1121–1133

    PubMed  CAS  Google Scholar 

  • Korgaonkar A, Trivedi U, Rumbaugh K et al (2013) Community surveillance enhances Pseudomonas aeruginosa virulence during polymicrobial infection. Proc Natl Acad Sci USA 110(3):1059–1064

    PubMed  CAS  Google Scholar 

  • Kreamer NNK, Wilks JC, Marlow JJ et al (2012) BqsR/BqsS constitute a two-component system that senses extracellular Fe(II) in Pseudomonas aeruginosa. J Bacteriol 194(5):1195–1204

    PubMed  CAS  Google Scholar 

  • Lau GW, Hassett DJ, Ran H et al (2004) The role of pyocyanin in Pseudomonas aeruginosa infection. Trends Mol Med 10(12):599–606

    PubMed  CAS  Google Scholar 

  • Lauredo IT, Sabater JR, Ahmed A et al (1998) Mechanism of pyocyanin- and 1-hydroxyphenazine-induced lung neutrophilia in sheep airways. J Appl Physiol 85(6):2298–2304

    PubMed  CAS  Google Scholar 

  • Laursen JB, Nielsen J (2004) Phenazine natural products: biosynthesis, synthetic analogues, and biological activity. Chem Rev 104:1663–1685

    PubMed  CAS  Google Scholar 

  • Leclair LW, Hogan DA (2010) Mixed bacterial-fungal infections in the CF respiratory tract. Med Mycol 48(Suppl 1):S125–S132

    PubMed  Google Scholar 

  • Leeman M, Van Pelt JA, Den Ouden FM et al (1995) Induction of systemic resistance against Fusarium wilt of radish by lipopolysaccharides of Pseudomonas fluorescens. Phytopathology 85:1021–1027

    CAS  Google Scholar 

  • Leidal KG, Munson KL, Denning GM (2001) Small molecular weight secretory factors from Pseudomonas aeruginosa have opposite effects on IL-8 and RANTES expression by human airway epithelial cells. Am J Respir Cell Mol Biol 25(2):186–195

    PubMed  CAS  Google Scholar 

  • Liu GY, Nizet V (2009) Color me bad: microbial pigments as virulence factors. Trends Microbiol 17(9):406–413

    PubMed  CAS  Google Scholar 

  • Lo HJ, Köhler JR, DiDomenico B et al (1997) Nonfilamentous C. albicans mutants are avirulent. Cell 90(5):939–949

    PubMed  CAS  Google Scholar 

  • Maddula VSRK, Pierson EA, Pierson LS (2008) Altering the ratio of phenazines in Pseudomonas chlororaphis (aureofaciens) strain 30-84: effects on biofilm formation and pathogen inhibition. J Bacteriol 190(8):2759–2766

    PubMed  CAS  Google Scholar 

  • Mahajan-Miklos S, Tan MW, Rahme LG et al (1999) Molecular mechanisms of bacterial virulence elucidated using a Pseudomonas aeruginosa-Caenorhabditis elegans pathogenesis model. Cell 96(1):47–56

    PubMed  CAS  Google Scholar 

  • Makgatho ME et al (2000) Tetramethylpiperidine-substituted phenazines as novel anti-plasmodial agents. Drug Dev Res 50(2):195–202

    CAS  Google Scholar 

  • Marks MI (1990) Clinical significance of Staphylococcus aureus in cystic fibrosis. Infection 18(1):53–56

    PubMed  CAS  Google Scholar 

  • Mavrodi DV, Peever TL, Mavrodi OV et al (2010) Diversity and evolution of the phenazine biosynthesis pathway. Appl Environ Microbiol 76:866–879

    PubMed  CAS  Google Scholar 

  • Mavrodi DV, Parejko JA, Mavrodi OV et al (2012) Recent insights into the diversity, frequency and ecological roles of phenazines in fluorescent Pseudomonas spp. Environ Microbiol 15(3):675–686

    PubMed  Google Scholar 

  • Mazzola M, Cook RJ, Thomashow LS et al (1992) Contribution of phenazine antibiotic synthesis to the ecological competence of fluorescent pseudomonads in soil habitats. Appl Environ Microbiol 58:2616–2624

    PubMed  CAS  Google Scholar 

  • McNamara PJ, Proctor RA (2006) Bacterial interactions and the microevolution of cytochrome bd: implications for pathogenesis. J Bacteriol 188(23):7997–7998

    PubMed  CAS  Google Scholar 

  • Mentel M, Ahuja EG, Mavrodi DV et al (2009) Of two make one: the biosynthesis of phenazines. ChemBioChem 10(14):2295–2304

    PubMed  CAS  Google Scholar 

  • Miller KM, Dearborn DG, Sorensen RU (1987) In vitro effect of synthetic pyocyanine on neutrophil superoxide production. Infect Immun 55(3):559–563

    PubMed  CAS  Google Scholar 

  • Mitchell AP (1988) Dimorphism and virulence in Candida albicans. Curr Opin Microbiol 1(6):687–692

    Google Scholar 

  • Morales DK, Jacobs NJ, Rajamani S et al (2010) Antifungal mechanisms by which a novel Pseudomonas aeruginosa phenazine toxin kills Candida albicans in biofilms. Mol Microbiol 78(6):1379–1392

    PubMed  CAS  Google Scholar 

  • Morales DK, Grahl N, Okegbe C et al (2013) Control of Candida albicans metabolism and biofilm formation by Pseudomonas aeruginosa phenazines. mBIO 4(1):e00526–e00612

    Google Scholar 

  • Moreau-Marquis S, O’Toole GA, Stanton BA (2009) Tobramycin and FDA-approved iron chelators eliminate Pseudomonas aeruginosa biofilms on cystic fibrosis cells. Am J Respir Cell Mol Biol 41(3):305–313

    PubMed  CAS  Google Scholar 

  • Moree WJ, Phelan VV, Wu CH et al (2012) Interkingdom metabolic transformations captured by microbial imaging mass spectrometry. Proc Natl Acad Sci USA 109(34):13811–13816

    Google Scholar 

  • Muhlradt PF, Tsai H, Conradt P (1986) Effects of pyocyanine, a blue pigment from Pseudomonas aeruginosa, on separate steps of T cell activation: interleukin 2 (IL 2) production, IL 2 receptor formation, proliferation and induction of cytolytic activity. Eur J Immunol 16(4):434–440

    PubMed  CAS  Google Scholar 

  • Musk DJ, Banko DA, Hergenrother PJ (2005) Iron salts perturb biofilm formation and disrupt existing biofilms of Pseudomonas aeruginosa. Chem Biol 12(7):789–796

    PubMed  CAS  Google Scholar 

  • Nabi ZF, Rabinovitch M (1984) Inhibition by superoxide dismutase and catalase of the damage of isolated Leishmania mexicana amazonensis by phenazine methosulfate. Mol Biochem Parasitol 10(3):297–303

    PubMed  CAS  Google Scholar 

  • Navarro J, Rainisio M, Harms HK et al (2001) Factors associated with poor pulmonary function: cross-sectional analysis of data from the ERCF. Eur Respir J 18(2):298–305

    PubMed  CAS  Google Scholar 

  • O’Malley YQ, Abdalla MY, McCormick ML et al (2003a) Subcellular localization of Pseudomonas pyocyanin cytotoxicity in human lung epithelial cells. Am J Physiol Lung Cell Mol Physiol 284(2):L420–L430

    PubMed  Google Scholar 

  • O’Malley YQ, Reszka KJ, Rasmussen GT et al (2003b) The Pseudomonas secretory product pyocyanin inhibits catalase activity in human lung epithelial cells. Am J Physiol Lung Cell Mol Physiol 285(5):L1077–L1086

    PubMed  Google Scholar 

  • Parejko JA, Mavrodi DV, Mavrodi OV et al (2012) Population structure and diversity of phenazine-1-carboxylic acid-producing fluorescent Pseudomonas spp. from dryland cereal fields of central Washington State (USA). Microb Ecol 64:226–241

    PubMed  Google Scholar 

  • Phillips DA, Fox TC, King MD et al (2004) Microbial products trigger amino acid exudation from plant roots. Plant Physiol 136(1):2887–2894

    PubMed  CAS  Google Scholar 

  • Pieterse CMJ, Van Pelt JA, Van Wees SCM et al (2001) Rhizobacteria-mediated induced systemic resistance: triggering, signalling and expression. Eur J Plant Pathol 107(1):51–61

    Google Scholar 

  • Price-Whelan A (2009) Physiology and mechanisms of pyocyanin reduction in Pseudomonas aeruginosa. Ph.D. Thesis, California Institute of Technology, USA

    Google Scholar 

  • Price-Whelan A, Dietrich LEP, Newman DK (2006) Rethinking ‘secondary’ metabolism: physiological roles for phenazine antibiotics. Nature Chem Biol 2(2):71–78

    CAS  Google Scholar 

  • Price-Whelan A, Dietrich LEP, Newman DK (2007) Pyocyanin alters redox homeostasis and carbon flux through central metabolic pathways in Pseudomonas aeruginosa PA14. J Bacteriol 189(17):6372–6381

    PubMed  CAS  Google Scholar 

  • Proctor RA, von Eiff C, Kahl BC et al (2006) Small colony variants: a pathogenic form of bacteria that facilitates persistent and recurrent infections. Nat Rev Microbiol 4(4):295–305

    PubMed  CAS  Google Scholar 

  • Rabaey K, Boon N, Siciliano SD et al (2004) Biofuel cells select for microbial consortia that self-mediate electron transfer. Appl Environ Microbiol 70(9):5373–5382

    PubMed  CAS  Google Scholar 

  • Rabaey K, Boon N, Höfte M et al (2005) Microbial phenazine production enhances electron transfer in biofuel cells. Environ Sci Technol 39(9):3401–3408

    PubMed  CAS  Google Scholar 

  • Rabinovitch M, Dedet JP, Ryter A et al (1982) Destruction of Leishmania mexicana amazonensis amastigotes within macrophages in culture by phenazine methosulfate and other electron carriers. J Exp Med 155(2):415–431

    PubMed  CAS  Google Scholar 

  • Rada B, Leto TL (2013) Pyocyanin effects on respiratory epithelium: relevance in Pseudomonas aeruginosa airway infections. Trends Microbiol (21)2:73–81

    Google Scholar 

  • Rada B, Lekstrom K, Damian S et al (2008) The Pseudomonas toxin pyocyanin inhibits the dual oxidase-based antimicrobial system as it imposes oxidative stress on airway epithelial cells. J Immunol 181(7):4883–4893

    PubMed  CAS  Google Scholar 

  • Rada B, Gardina P, Myers TG et al (2011) Reactive oxygen species mediate inflammatory cytokine release and EGFR-dependent mucin secretion in airway epithelial cells exposed to Pseudomonas pyocyanin. Mucosal Immunol 4(2):158–171

    Google Scholar 

  • Ramos I, Dietrich LEP, Price-Whelan A et al (2010) Phenazines affect biofilm formation by Pseudomonas aeruginosa in similar ways at various scales. Res Microbiol 61:187–191

    Google Scholar 

  • Ran H, Hassett DJ, Lau GW (2003) Human targets of Pseudomonas aeruginosa pyocyanin. Proc Natl Acad Sci USA 100(24):14315–14320

    PubMed  CAS  Google Scholar 

  • Ratner D, Mueller C (2012) Immune responses in cystic fibrosis: are they intrinsically defective? Am J Respir Cell Mol Biol 46(6):715–722

    PubMed  CAS  Google Scholar 

  • Recinos DA, Sekedat MD, Hernandez A et al (2012) Redundant phenazine operons in Pseudomonas aeruginosa exhibit environment-dependent expression and differential roles in pathogenicity. Proc Natl Acad Sci USA 109(47):19420–19425

    PubMed  CAS  Google Scholar 

  • Rella A, Yang MW, Gruber J et al (2012) Pseudomonas aeruginosa inhibits the growth of Cryptococcus species. Mycopathologia 173(5–6):451–461

    PubMed  CAS  Google Scholar 

  • Sadik CD, Kim ND, Luster AD (2011) Neutrophils cascading their way to inflammation. Trends Immunol 32(10):452–460

    PubMed  CAS  Google Scholar 

  • Schoental R (1941) The nature of the antibacterial agents present in Pseudomonas pyocyanea cultures. Brit J Exp Pathol 1941(22):137–147

    Google Scholar 

  • Schwarzer C, Fischer H, Kim EJ et al (2008) Oxidative stress caused by pyocyanin impairs CFTR Cl transport in human bronchial epithelial cells. Free Radic Biol Med 45(12):1653–1662

    PubMed  CAS  Google Scholar 

  • Shipton PJ (1975) Take-all decline during cereal monoculture. In: Biology and control of soil borne plant pathogens international symposium (3d), pp 137–144

    Google Scholar 

  • Singh PK, Parsek MR, Greenberg EP et al (2002) A component of innate immunity prevents bacterial biofilm development. Nature 417(6888):552–555

    PubMed  CAS  Google Scholar 

  • Slininger PJ, Jackson MA (1992) Nutritional factors regulating growth and accumulation of phenazine 1-carboxylic acid by Pseudomonas fluorescens 2-79. Appl Microbiol Biotechnol 37:388–392

    CAS  Google Scholar 

  • Slininger PJ, Shea-Wilbur MA (1995) Liquid-culture pH, temperature, and carbon (not nitrogen) source regulate phenazine productivity of the take-all biocontrol agent Pseudomonas fluorescens 2-79. Appl Microbiol Biotechnol 43(5):794–800

    PubMed  CAS  Google Scholar 

  • Stewart PS, Franklin MJ (2008) Physiological heterogeneity in biofilms. Nat Rev Microbiol 6(3):199–210

    PubMed  CAS  Google Scholar 

  • Stewart-Tull DE, Armstrong A (1971) The effect of 1-hydroxyphenazine and pyocyanine from Pseudomonas aeruginosa on mammalian cell respiration. J Med Microbiol 5:67–73

    Google Scholar 

  • Sullivan NL, Tzeranis DS, Wang Y et al (2011) Quantifying the dynamics of bacterial secondary metabolites by spectral multiphoton microscopy. ACS Chem Biol 6(9):893–899

    PubMed  CAS  Google Scholar 

  • Thomashow LS, Weller DM (1988) Role of a phenazine antibiotic from Pseudomonas fluorescens in biological control of Gaeumannomyces graminis var. tritici. J Bacteriol 170(8):3499–3508

    PubMed  CAS  Google Scholar 

  • Thomashow LS, Weller DM, Bonsall RF et al (1990) Production of the antibiotic phenazine-1-carboxylic acid by fluorescent Pseudomonas species in the rhizosphere of wheat. Appl Environ Microbiol 56(4):908–912

    PubMed  CAS  Google Scholar 

  • Toohey JI, Nelson CD, Krotkov G (1965) Toxicity of phenazine carboxylic acids to some bacteria, algae, higher plants, and animals. Can J Bot 43(9):1151–1155

    CAS  Google Scholar 

  • Usher LR, Lawson RA, Geary I et al (2002) Induction of neutrophil apoptosis by the Pseudomonas aeruginosa exotoxin pyocyanin: a potential mechanism of persistent infection. J Immunol 168(4):1861–1868

    PubMed  CAS  Google Scholar 

  • Vagelas IK, Pembroke B, Gowen SR et al (2007) The control of root-knot nematodes (Meloidogyne spp.) by Pseudomonas oryzihabitans and its immunological detection on tomato roots. Nematology 9(3):363–370

    Google Scholar 

  • van Loon LC, Bakker PAHM, Pieterse CMJ (1998) Systemic resistance induced by rhizosphere bacteria. Annu Rev Phytopathol 36:453–483

    PubMed  Google Scholar 

  • van Rij ET, Wesselink M, Chin-A-Woeng TFC et al (2004) Influence of environmental conditions on the production of phenazine-1-carboxamide by Pseudomonas chlororaphis PCL1391. Mol Plant Microbe Interact 17:557–566

    PubMed  Google Scholar 

  • Venkataraman A, Rosenbaum MA, Perkins SD et al (2011) Metabolite-based mutualism between Pseudomonas aeruginosa PA14 and Enterobacter aerogenes enhances current generation in bioelectrochemical systems. Energy Environ Sci 4:4550–4559

    CAS  Google Scholar 

  • Voggu L, Schlag S, Biswas R et al (2006) Microevolution of cytochrome bd oxidase in staphylococci and its implication in resistance to respiratory toxins released by Pseudomonas. J Bacteriol 188(23):8079–8086

    PubMed  CAS  Google Scholar 

  • Wang Y, Newman DK (2008) Redox reactions of phenazine antibiotics with ferric (hydr)oxides and molecular oxygen. Environ Sci Technol 42(7):2380–2386

    PubMed  CAS  Google Scholar 

  • Wang Y, Kern SE, Newman DK (2010) Endogenous phenazine antibiotics promote anaerobic survival of Pseudomonas aeruginosa via extracellular electron transfer. J Bacteriol 192(1):365–369

    PubMed  CAS  Google Scholar 

  • Wang Y, Wilks JC, Danhorn T et al (2011) Phenazine-1-carboxylic acid promotes bacterial biofilm development via ferrous iron acquisition. J Bacteriol 193:3606–3617

    PubMed  CAS  Google Scholar 

  • Weller DM, Cook RJ (1983) Suppression of take-all of wheat by seed treatments with fluorescent pseudomonads. Phytopathology 73:463–469

    Google Scholar 

  • Wilson R, Sykes DA, Watson D et al (1988) Measurement of Pseudomonas aeruginosa phenazine pigments in sputum and assessment of their contribution to sputum sol toxicity for respiratory ephithelium. Infect Immun 56(9):2515–2517

    PubMed  CAS  Google Scholar 

  • Worlitzsch D, Tarran R, Ulrich M et al (2002) Effects of reduced mucus oxygen concentration in airway Pseudomonas infections of cystic fibrosis patients. J Clin Invest 109(3):317–325

    PubMed  CAS  Google Scholar 

  • Wurtzel O, Yoder-Himes DR, Han K et al (2012) The single-nucleotide resolution transcriptome of Pseudomonas aeruginosa grown in body temperature. PLoS Pathog 8(9):e1002945

    PubMed  Google Scholar 

  • Young G (1947) Pigment production and antibiotic activity in cultures of Pseudomonas aeruginosa. J Bacteriol 54(2):109–117

    PubMed  CAS  Google Scholar 

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Grahl, N., Kern, S.E., Newman, D.K., Hogan, D.A. (2013). The Yin and Yang of Phenazine Physiology. In: Chincholkar, S., Thomashow, L. (eds) Microbial Phenazines. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-40573-0_3

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