Chapter 9 : Metabolism and Pathogenicity of Infections in the Lungs of Individuals with Cystic Fibrosis

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The lung is typically considered a sterile environment; however, this is rarely true in practice. Healthy individuals constantly inhale various microbes, and the innate immune system is responsible for their removal through a system of mucocilliary clearance. Some individuals experience altered mucocilliary clearance due to any of a number of diseases, and one of the best-studied examples of this occurs in individuals with the genetic disease cystic fibrosis (CF). A hallmark phenotype of CF is dehydration of the mucosal layer across all epithelial surfaces inside the body, resulting in a thickening of the mucus that cannot be adequately cleared despite frequent expectoration. This mucus is an excellent growth substrate for a range of bacteria, and the lung disease associated with these infections further alters the mucus, resulting in a complex mixture of host and microbe derived macromolecules called sputum that is not present in healthy lungs. The opportunistic pathogen is generally the most difficult of these invaders to eradicate, and infections with this organism are the leading cause of morbidity and mortality for individuals with CF ( ).

Citation: Palmer G, Whiteley M. 2015. Metabolism and Pathogenicity of Infections in the Lungs of Individuals with Cystic Fibrosis, p 185-213. In Conway T, Cohen P (ed), Metabolism and Bacterial Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MBP-0003-2014
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1. Hoiby N . 1998. Pseudomonas in cystic fibrosis: past, present, and future. Cystic Fibrosis Trust, London, United Kingdom.
2. Lyczak JB,, Cannon CL,, Pier GB . 2002. Lung infections associated with cystic fibrosis. Clin Microbiol Rev 15 : 194222.[PubMed] [CrossRef]
3. Anderson MP,, Gregory RJ,, Thompson S,, Souza DW,, Paul S,, Mulligan RC,, Smith AE,, Welsh MJ . 1991. Demonstration that CFTR is a chloride channel by alteration of its anion selectivity. Science 253 : 202205.[PubMed] [CrossRef]
4. Riordan JR,, Rommens JM,, Kerem B,, Alon N,, Rozmahel R,, Grzelczak Z,, Zielenski J,, Lok S,, Plavsic N,, Chou JL , , et al . 1989. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science 245 : 10661073.[PubMed] [CrossRef]
5. Reddy MM,, Light MJ,, Quinton PM . 1999. Activation of the epithelial Na+ channel (ENaC) requires CFTR Cl- channel function. Nature 402 : 301304.[PubMed] [CrossRef]
6. Schwiebert EM,, Egan ME,, Hwang TH,, Fulmer SB,, Allen SS,, Cutting GR,, Guggino WB . 1995. CFTR regulates outwardly rectifying chloride channels through an autocrine mechanism involving ATP. Cell 81 : 10631073.[PubMed] [CrossRef]
7. Collawn JF,, Fu L,, Bebok Z . 2010. Targets for cystic fibrosis therapy: proteomic analysis and correction of mutant cystic fibrosis transmembrane conductance regulator. Expert Rev Proteomics 7 : 495506.[PubMed] [CrossRef]
8. Kreda SM,, Mall M,, Mengos A,, Rochelle L,, Yankaskas J,, Riordan JR,, Boucher RC . 2005. Characterization of wild-type and deltaF508 cystic fibrosis transmembrane regulator in human respiratory epithelia. Mol Biol Cell 16 : 21542167.[PubMed] [CrossRef]
9. Tucker TA,, Fortenberry JA,, Zsembery A,, Schwiebert LM,, Schwiebert EM . 2012. The DeltaF508-CFTR mutation inhibits wild-type CFTR processing and function when co-expressed in human airway epithelia and in mouse nasal mucosa. BMC Physiol 12 : 12. [PubMed] [CrossRef]
10. Derichs N . 2013. Targeting a genetic defect: cystic fibrosis transmembrane conductance regulator modulators in cystic fibrosis. Eur Respir Rev 22 : 5865.[PubMed] [CrossRef]
11. Pier GB,, Grout M,, Zaidi TS,, Olsen JC,, Johnson LG,, Yankaskas JR,, Goldberg JB . 1996. Role of mutant CFTR in hypersusceptibility of cystic fibrosis patients to lung infections. Science 271 : 6467.[PubMed] [CrossRef]
12. Hallows KR,, Fitch AC,, Richardson CA,, Reynolds PR,, Clancy JP,, Dagher PC,, Witters LA,, Kolls JK,, Pilewski JM . 2006. Up-regulation of AMP-activated kinase by dysfunctional cystic fibrosis transmembrane conductance regulator in cystic fibrosis airway epithelial cells mitigates excessive inflammation. J Biol Chem 281 : 42314241.[PubMed] [CrossRef]
13. de Montalembert M,, Fauchere JL,, Bourdon R,, Lenoir G,, Rey J . 1989. [Iron deficiency and Pseudomonas aeruginosa colonization in cystic fibrosis]. Arch Fr Pediatr 46 : 331334.[PubMed]
14. Moreau-Marquis S,, Bomberger JM,, Anderson GG,, Swiatecka-Urban A,, Ye S,, O’Toole GA,, Stanton BA . 2008. The DeltaF508-CFTR mutation results in increased biofilm formation by Pseudomonas aeruginosa by increasing iron availability. Am J Physiol Lung Cell Mol Physiol 295 : L25L37.[PubMed] [CrossRef]
15. Palmer KL,, Aye LM,, Whiteley M . 2007. Nutritional cues control Pseudomonas aeruginosa multicellular behavior in cystic fibrosis sputum. J Bacteriol 189 : 80798087.[PubMed] [CrossRef]
16. Reid DW,, Withers NJ,, Francis L,, Wilson JW,, Kotsimbos TC . 2002. Iron deficiency in cystic fibrosis: relationship to lung disease severity and chronic Pseudomonas aeruginosa infection. Chest 121 : 4854.[PubMed] [CrossRef]
17. Stites SW,, Plautz MW,, Bailey K,, O’Brien-Ladner AR,, Wesselius LJ . 1999. Increased concentrations of iron and isoferritins in the lower respiratory tract of patients with stable cystic fibrosis. Am J Respir Crit Care Med 160 : 796801.[PubMed] [CrossRef]
18. Stites SW,, Walters B,, O’Brien-Ladner AR,, Bailey K,, Wesselius LJ . 1998. Increased iron and ferritin content of sputum from patients with cystic fibrosis or chronic bronchitis. Chest 114 : 814819.[PubMed] [CrossRef]
19. Kirkham S,, Sheehan JK,, Knight D,, Richardson PS,, Thornton DJ . 2002. Heterogeneity of airways mucus: variations in the amounts and glycoforms of the major oligomeric mucins MUC5AC and MUC5B. Biochem J 361 : 537546.[PubMed] [CrossRef]
20. Rogers DF,, Lethem MI . 1997. Airway mucus : basic mechanisms and clinical perspectives. Birkhauser, Basel; Boston, MA. [CrossRef]
21. Voynow JA,, Rubin BK . 2009. Mucins, mucus, and sputum. Chest 135 : 505512.[PubMed] [CrossRef]
22. Fahy JV,, Steiger DJ,, Liu J,, Basbaum CB,, Finkbeiner WE,, Boushey HA . 1993. Markers of mucus secretion and DNA levels in induced sputum from asthmatic and from healthy subjects. Am Rev Respir Dis 147 : 11321137.[PubMed] [CrossRef]
23. Henke MO,, Renner A,, Huber RM,, Seeds MC,, Rubin BK . 2004. MUC5AC and MUC5B Mucins Are Decreased in Cystic Fibrosis Airway Secretions. Am J Respir Cell Mol Biol 31 : 8691.[PubMed] [CrossRef]
24. Henke MO,, John G,, Germann M,, Lindemann H,, Rubin BK . 2007. MUC5AC and MUC5B mucins increase in cystic fibrosis airway secretions during pulmonary exacerbation. Am J Respir Crit Care Med 175 : 816821.[PubMed] [CrossRef]
25. Li S,, Intini G,, Bobek LA . 2006. Modulation of MUC7 mucin expression by exogenous factors in airway cells in vitro and in vivo. Am J Respir Cell Mol Biol 35 : 95102.[PubMed] [CrossRef]
26. Kohri K,, Ueki IF,, Shim JJ,, Burgel PR,, Oh YM,, Tam DC,, Dao-Pick T,, Nadel JA . 2002. Pseudomonas aeruginosa induces MUC5AC production via epidermal growth factor receptor. Eur Respir J 20 : 12631270.[PubMed] [CrossRef]
27. Song JS,, Hyun SW,, Lillihoj E,, Kim BT . 2001. Mucin secretion in the rat tracheal epithelial cells by epidermal growth factor and Pseudomonas aeruginosa extracts. Korean J Intern Med 16 : 167172.[PubMed]
28. Yan F,, Li W,, Jono H,, Li Q,, Zhang S,, Li JD,, Shen H . 2008. Reactive oxygen species regulate Pseudomonas aeruginosa lipopolysaccharide-induced MUC5AC mucin expression via PKC-NADPH oxidase-ROS-TGF-alpha signaling pathways in human airway epithelial cells. Biochem Biophys Res Commun 366 : 513519.[PubMed] [CrossRef]
29. Hao Y,, Kuang Z,, Walling BE,, Bhatia S,, Sivaguru M,, Chen Y,, Gaskins HR,, Lau GW . 2012. Pseudomonas aeruginosa pyocyanin causes airway goblet cell hyperplasia and metaplasia and mucus hypersecretion by inactivating the transcriptional factor FoxA2. Cell Microbiol 14 : 401415.[PubMed] [CrossRef]
30. Carnoy C,, Ramphal R,, Scharfman A,, Lo-Guidice JM,, Houdret N,, Klein A,, Galabert C,, Lamblin G,, Roussel P . 1993. Altered carbohydrate composition of salivary mucins from patients with cystic fibrosis and the adhesion of Pseudomonas aeruginosa . Am J Respir Cell Mol Biol 9 : 323334.[PubMed] [CrossRef]
31. Glasser JR,, Mallampalli RK . 2012. Surfactant and its role in the pathobiology of pulmonary infection. Microbes Infect 14 : 1725.[PubMed] [CrossRef]
32. Guillot L,, Nathan N,, Tabary O,, Thouvenin G,, Le Rouzic P,, Corvol H,, Amselem S,, Clement A . 2013. Alveolar epithelial cells: Master regulators of lung homeostasis. Int J Biochem Cell Biol 45 : 25682573.[PubMed] [CrossRef]
33. Proud D . 2008. The pulmonary epithelium in health and disease. John Wiley & Sons, Chichester, England ; Hoboken, NJ. [CrossRef]
34. Griese M,, App EM,, Duroux A,, Burkert A,, Schams A . 1997. Recombinant human DNase (rhDNase) influences phospholipid composition, surface activity, rheology and consecutively clearance indices of cystic fibrosis sputum. Pulm Pharmacol Ther 10 : 2127.[PubMed] [CrossRef]
35. Hull J,, South M,, Phelan P,, Grimwood K . 1997. Surfactant composition in infants and young children with cystic fibrosis. Am J Respir Crit Care Med 156 : 161165.[PubMed] [CrossRef]
36. Gilljam H,, Andersson O,, Ellin A,, Robertson B,, Strandvik B . 1988. Composition and surface properties of the bronchial lipids in adult patients with cystic fibrosis. Clin Chim Acta 176 : 2937.[PubMed] [CrossRef]
37. Girod S,, Galabert C,, Lecuire A,, Zahm JM,, Puchelle E . 1992. Phospholipid composition and surface-active properties of tracheobronchial secretions from patients with cystic fibrosis and chronic obstructive pulmonary diseases. Pediatr Pulmonol 13 : 2227.[PubMed] [CrossRef]
38. Meyer KC,, Sharma A,, Brown R,, Weatherly M,, Moya FR,, Lewandoski J,, Zimmerman JJ . 2000. Function and composition of pulmonary surfactant and surfactant-derived fatty acid profiles are altered in young adults with cystic fibrosis. Chest 118 : 164174.[PubMed] [CrossRef]
39. Griese M,, Birrer P,, Demirsoy A . 1997. Pulmonary surfactant in cystic fibrosis. Eur Respir J 10 : 19831988.[PubMed] [CrossRef]
40. Lethem MI,, James SL,, Marriott C,, Burke JF . 1990. The origin of DNA associated with mucus glycoproteins in cystic fibrosis sputum. Eur Respir J 3 : 1923.[PubMed]
41. Brandt T,, Breitenstein S,, von der Hardt H,, Tummler B . 1995. DNA concentration and length in sputum of patients with cystic fibrosis during inhalation with recombinant human DNase. Thorax 50 : 880882.[PubMed] [CrossRef]
42. Kirchner KK,, Wagener JS,, Khan TZ,, Copenhaver SC,, Accurso FJ . 1996. Increased DNA levels in bronchoalveolar lavage fluid obtained from infants with cystic fibrosis. Am J Respir Crit Care Med 154 : 14261429.[PubMed] [CrossRef]
43. Ratjen F,, Paul K,, van Koningsbruggen S,, Breitenstein S,, Rietschel E,, Nikolaizik W . 2005. DNA concentrations in BAL fluid of cystic fibrosis patients with early lung disease: influence of treatment with dornase alpha. Pediatr Pulmonol 39 : 14.[PubMed] [CrossRef]
44. Wagener JS,, Rock MJ,, McCubbin MM,, Hamilton SD,, Johnson CA,, Ahrens RC . 1998. Aerosol delivery and safety of recombinant human deoxyribonuclease in young children with cystic fibrosis: a bronchoscopic study. Pulmozyme Pediatric Broncoscopy Study Group. J Pediatr 133 : 486491.[PubMed] [CrossRef]
45. Riethmueller J,, Vonthein R,, Borth-Bruhns T,, Grassme H,, Eyrich M,, Schilbach K,, Stern M,, Gulbins E . 2008. DNA quantification and fragmentation in sputum after inhalation of recombinant human deoxyribonuclease. Cell Physiol Biochem 22 : 347352.[PubMed] [CrossRef]
46. Smith AL,, Redding G,, Doershuk C,, Goldmann D,, Gore E,, Hilman B,, Marks M,, Moss R,, Ramsey B,, Rubio T , , et al . 1988. Sputum changes associated with therapy for endobronchial exacerbation in cystic fibrosis. J Pediatr 112 : 547554.[PubMed] [CrossRef]
47. Bensel T,, Stotz M,, Borneff-Lipp M,, Wollschlager B,, Wienke A,, Taccetti G,, Campana S,, Meyer KC,, Jensen PO,, Lechner U,, Ulrich M,, Doring G,, Worlitzsch D . 2011. Lactate in cystic fibrosis sputum. J Cyst Fibros 10 : 3744.[PubMed] [CrossRef]
48. Wolak JE,, Esther CR Jr,, O’Connell TM . 2009. Metabolomic analysis of bronchoalveolar lavage fluid from cystic fibrosis patients. Biomarkers 14 : 5560.[PubMed] [CrossRef]
49. Korgaonkar AK,, Whiteley M . 2011. Pseudomonas aeruginosa enhances production of an antimicrobial in response to N-acetylglucosamine and peptidoglycan. J Bacteriol 193 : 909917.[PubMed] [CrossRef]
50. Postle AD,, Mander A,, Reid KB,, Wang JY,, Wright SM,, Moustaki M,, Warner JO . 1999. Deficient hydrophilic lung surfactant proteins A and D with normal surfactant phospholipid molecular species in cystic fibrosis. Am J Respir Cell Mol Biol 20 : 9098.[PubMed] [CrossRef]
51. Sloane AJ,, Lindner RA,, Prasad SS,, Sebastian LT,, Pedersen SK,, Robinson M,, Bye PT,, Nielson DW,, Harry JL . 2005. Proteomic analysis of sputum from adults and children with cystic fibrosis and from control subjects. Am J Respir Crit Care Med 172 : 14161426.[PubMed] [CrossRef]
52. McMorran BJ,, Patat SA,, Carlin JB,, Grimwood K,, Jones A,, Armstrong DS,, Galati JC,, Cooper PJ,, Byrnes CA,, Francis PW,, Robertson CF,, Hume DA,, Borchers CH,, Wainwright CE,, Wainwright BJ . 2007. Novel neutrophil-derived proteins in bronchoalveolar lavage fluid indicate an exaggerated inflammatory response in pediatric cystic fibrosis patients. Clin Chem 53 : 17821791.[PubMed] [CrossRef]
53. Barth AL,, Pitt TL . 1996. The high amino-acid content of sputum from cystic fibrosis patients promotes growth of auxotrophic Pseudomonas aeruginosa . J Med Microbiol 45 : 110119.[PubMed] [CrossRef]
54. Dosanjh A,, Lakhani S,, Elashoff D,, Chin C,, Hsu V,, Hilman B . 2000. A comparison of microbiologic flora of the sinuses and airway among cystic fibrosis patients with maxillary antrostomies. Pediatr Transplant 4 : 182185. [PubMed] [CrossRef]
55. Lavin J,, Bhushan B,, Schroeder JW Jr . 2013. Correlation between respiratory cultures and sinus cultures in children with cystic fibrosis. Int J Pediatr Otorhinolaryngol 77 : 686689.[PubMed] [CrossRef]
56. Roby BB,, McNamara J,, Finkelstein M,, Sidman J . 2008. Sinus surgery in cystic fibrosis patients: comparison of sinus and lower airway cultures. Int J Pediatr Otorhinolaryngol 72 : 13651369.[PubMed] [CrossRef]
57. Ciofu O,, Hansen CR,, Hoiby N . 2013. Respiratory bacterial infections in cystic fibrosis. Curr Opin Pulm Med 19 : 251258.[PubMed] [CrossRef]
58. Fuqua C,, Winans SC,, Greenberg EP . 1996. Census and consensus in bacterial ecosystems: the LuxR-LuxI family of quorum-sensing transcriptional regulators. Annu Rev Microbiol 50 : 727751.[PubMed] [CrossRef]
59. Fuqua WC,, Winans SC,, Greenberg EP . 1994. Quorum sensing in bacteria: the LuxR-LuxI family of cell density-responsive transcriptional regulators. J Bacteriol 176 : 269275.[PubMed]
60. Pearson JP,, Gray KM,, Passador L,, Tucker KD,, Eberhard A,, Iglewski BH,, Greenberg EP . 1994. Structure of the autoinducer required for expression of Pseudomonas aeruginosa virulence genes. Proc Natl Acad Sci USA 91 : 197201.[PubMed] [CrossRef]
61. Passador L,, Cook JM,, Gambello MJ,, Rust L,, Iglewski BH . 1993. Expression of Pseudomonas aeruginosa virulence genes requires cell-to-cell communication. Science 260 : 11271130.[PubMed] [CrossRef]
62. Gambello MJ,, Iglewski BH . 1991. Cloning and characterization of the Pseudomonas aeruginosa lasR gene, a transcriptional activator of elastase expression. J Bacteriol 173 : 30003009.[PubMed]
63. Ochsner UA,, Koch AK,, Fiechter A,, Reiser J . 1994. Isolation and characterization of a regulatory gene affecting rhamnolipid biosurfactant synthesis in Pseudomonas aeruginosa . J Bacteriol 176 : 20442054.[PubMed]
64. Ochsner UA,, Reiser J . 1995. Autoinducer-mediated regulation of rhamnolipid biosurfactant synthesis in Pseudomonas aeruginosa . Proc Natl Acad Sci USA 92 : 64246428.[PubMed] [CrossRef]
65. Pearson JP,, Passador L,, Iglewski BH,, Greenberg EP . 1995. A second N-acylhomoserine lactone signal produced by Pseudomonas aeruginosa . Proc Natl Acad Sci USA 92 : 14901494. [PubMed] [CrossRef]
66. Pesci EC,, Milbank JB,, Pearson JP,, McKnight S,, Kende AS,, Greenberg EP,, Iglewski BH . 1999. Quinolone signaling in the cell-to-cell communication system of Pseudomonas aeruginosa . Proc Natl Acad Sci USA 96 : 1122911234.[PubMed] [CrossRef]
67. Xiao G,, Deziel E,, He J,, Lepine F,, Lesic B,, Castonguay MH,, Milot S,, Tampakaki AP,, Stachel SE,, Rahme LG . 2006. MvfR, a key Pseudomonas aeruginosa pathogenicity LTTR-class regulatory protein, has dual ligands. Mol Microbiol 62 : 16891699.[PubMed] [CrossRef]
68. Cao H,, Krishnan G,, Goumnerov B,, Tsongalis J,, Tompkins R,, Rahme LG . 2001. A quorum sensing-associated virulence gene of Pseudomonas aeruginosa encodes a LysR-like transcription regulator with a unique self-regulatory mechanism. Proc Natl Acad Sci USA 98 : 1461314618.[PubMed] [CrossRef]
69. Schuster M,, Greenberg EP . 2006. A network of networks: quorum-sensing gene regulation in Pseudomonas aeruginosa . Int J Med Microbiol 296 : 7381.[PubMed] [CrossRef]
70. Duan K,, Surette MG . 2007. Environmental regulation of Pseudomonas aeruginosa PAO1 Las and Rhl quorum-sensing systems. J Bacteriol 189 : 48274836.[PubMed] [CrossRef]
71. Palmer KL,, Mashburn LM,, Singh PK,, Whiteley M . 2005. Cystic fibrosis sputum supports growth and cues key aspects of Pseudomonas aeruginosa physiology. J Bacteriol 187 : 52675277.[PubMed] [CrossRef]
72. Liu PV . 1966. The roles of various fractions of Pseudomonas aeruginosa in its pathogenesis. 3. Identity of the lethal toxins produced in vitro and in vivo. J Infect Dis 116 : 481489.[PubMed] [CrossRef]
73. Liu PV . 1966. The roles of various fractions of Pseudomonas aeruginosa in its pathogenesis. II. Effects of lecithinase and protease. J Infect Dis 116 : 112116.[PubMed] [CrossRef]
74. Liu PV,, Abe Y,, Bates JL . 1961. The roles of various fractions of Pseudomonas aeruginosa in its pathogenesis. J Infect Dis 108 : 218228.[PubMed] [CrossRef]
75. Jordan EO . 1899. Bacillus Pyocyaneus and Its Pigments. J Exp Med 4 : 627647.[PubMed] [CrossRef]
76. Bleves S,, Viarre V,, Salacha R,, Michel GP,, Filloux A,, Voulhoux R . 2010. Protein secretion systems in Pseudomonas aeruginosa: A wealth of pathogenic weapons. Int J Med Microbiol 300 : 534543.[PubMed] [CrossRef]
77. Duong F,, Lazdunski A,, Murgier M . 1996. Protein secretion by heterologous bacterial ABC-transporters: the C-terminus secretion signal of the secreted protein confers high recognition specificity. Mol Microbiol 21 : 459470.[PubMed] [CrossRef]
78. Letoffe S,, Redeker V,, Wandersman C . 1998. Isolation and characterization of an extracellular haem-binding protein from Pseudomonas aeruginosa that shares function and sequence similarities with the Serratia marcescens HasA haemophore. Mol Microbiol 28 : 12231234.[PubMed] [CrossRef]
79. Iglewski BH,, Kabat D . 1975. NAD-dependent inhibition of protein synthesis by Pseudomonas aeruginosa toxin. Proc Natl Acad Sci USA 72 : 22842288.[PubMed] [CrossRef]
80. Frank DW . 1997. The exoenzyme S regulon of Pseudomonas aeruginosa . Mol Microbiol 26 : 621629.[PubMed] [CrossRef]
81. Yahr TL,, Goranson J,, Frank DW . 1996. Exoenzyme S of Pseudomonas aeruginosa is secreted by a type III pathway. Mol Microbiol 22 : 9911003.[PubMed] [CrossRef]
82. Yahr TL,, Mende-Mueller LM,, Friese MB,, Frank DW . 1997. Identification of type III secreted products of the Pseudomonas aeruginosa exoenzyme S regulon. J Bacteriol 179 : 71657168.[PubMed]
83. Lee VT,, Smith RS,, Tummler B,, Lory S . 2005. Activities of Pseudomonas aeruginosa effectors secreted by the Type III secretion system in vitro and during infection. Infect Immun 73 : 16951705.[PubMed] [CrossRef]
84. Russell AB,, LeRoux M,, Hathazi K,, Agnello DM,, Ishikawa T,, Wiggins PA,, Wai SN,, Mougous JD . 2013. Diverse type VI secretion phospholipases are functionally plastic antibacterial effectors. Nature 496 : 508512.[PubMed] [CrossRef]
85. Russell AB,, Hood RD,, Bui NK,, LeRoux M,, Vollmer W,, Mougous JD . 2011. Type VI secretion delivers bacteriolytic effectors to target cells. Nature 475 : 343347.[PubMed] [CrossRef]
86. Mougous JD,, Cuff ME,, Raunser S,, Shen A,, Zhou M,, Gifford CA,, Goodman AL,, Joachimiak G,, Ordonez CL,, Lory S,, Walz T,, Joachimiak A,, Mekalanos JJ . 2006. A virulence locus of Pseudomonas aeruginosa encodes a protein secretion apparatus. Science 312 : 15261530.[PubMed] [CrossRef]
87. Bomberger JM,, Maceachran DP,, Coutermarsh BA,, Ye S,, O’Toole GA,, Stanton BA . 2009. Long-distance delivery of bacterial virulence factors by Pseudomonas aeruginosa outer membrane vesicles. PLoS Pathog 5 : e1000382. [PubMed] [CrossRef]
88. Kadurugamuwa JL,, Beveridge TJ . 1995. Virulence factors are released from Pseudomonas aeruginosa in association with membrane vesicles during normal growth and exposure to gentamicin: a novel mechanism of enzyme secretion. J Bacteriol 177 : 39984008.[PubMed]
89. Beveridge TJ . 1999. Structures of gram-negative cell walls and their derived membrane vesicles. J Bacteriol 181 : 47254733.[PubMed]
90. Mashburn LM,, Whiteley M . 2005. Membrane vesicles traffic signals and facilitate group activities in a prokaryote. Nature 437 : 422425.[PubMed] [CrossRef]
91. Suter S,, Schaad UB,, Tegner H,, Ohlsson K,, Desgrandchamps D,, Waldvogel FA . 1986. Levels of free granulocyte elastase in bronchial secretions from patients with cystic fibrosis: effect of antimicrobial treatment against Pseudomonas aeruginosa . J Infect Dis 153 : 902909.[PubMed] [CrossRef]
92. Voynow JA,, Fischer BM,, Zheng S . 2008. Proteases and cystic fibrosis. Int J Biochem Cell Biol 40 : 12381245.[PubMed] [CrossRef]
93. Smith RS,, Iglewski BH . 2003. P. aeruginosa quorum-sensing systems and virulence. Curr Opin Microbiol 6 : 5660.[PubMed] [CrossRef]
94. Nouwens AS,, Beatson SA,, Whitchurch CB,, Walsh BJ,, Schweizer HP,, Mattick JS,, Cordwell SJ . 2003. Proteome analysis of extracellular proteins regulated by the las and rhl quorum sensing systems in Pseudomonas aeruginosa PAO1. Microbiology 149 : 13111322.[PubMed] [CrossRef]
95. Scott NE,, Hare NJ,, White MY,, Manos J,, Cordwell SJ . 2013. Secretome of Transmissible Pseudomonas aeruginosa AES-1R Grown in a Cystic Fibrosis Lung-Like Environment. J Proteome Res 12(12): 53575369.[PubMed] [CrossRef]
96. Butterworth MB,, Zhang L,, Heidrich EM,, Myerburg MM,, Thibodeau PH . 2012. Activation of the epithelial sodium channel (ENaC) by the alkaline protease from Pseudomonas aeruginosa . J Biol Chem 287 : 3255632565.[PubMed] [CrossRef]
97. Terada LS,, Johansen KA,, Nowbar S,, Vasil AI,, Vasil ML . 1999. Pseudomonas aeruginosa hemolytic phospholipase C suppresses neutrophil respiratory burst activity. Infect Immun 67 : 23712376.[PubMed]
98. Ostroff RM,, Wretlind B,, Vasil ML . 1989. Mutations in the hemolytic-phospholipase C operon result in decreased virulence of Pseudomonas aeruginosa PAO1 grown under phosphate-limiting conditions. Infect Immun 57 : 13691373.[PubMed]
99. Ostroff RM,, Vasil AI,, Vasil ML . 1990. Molecular comparison of a nonhemolytic and a hemolytic phospholipase C from Pseudomonas aeruginosa . J Bacteriol 172 : 59155923.[PubMed]
100. Barker AP,, Vasil AI,, Filloux A,, Ball G,, Wilderman PJ,, Vasil ML . 2004. A novel extracellular phospholipase C of Pseudomonas aeruginosa is required for phospholipid chemotaxis. Mol Microbiol 53 : 10891098.[PubMed] [CrossRef]
101. MacEachran DP,, Ye S,, Bomberger JM,, Hogan DA,, Swiatecka-Urban A,, Stanton BA,, O’Toole GA . 2007. The Pseudomonas aeruginosa secreted protein PA2934 decreases apical membrane expression of the cystic fibrosis transmembrane conductance regulator. Infect Immun 75 : 39023912.[PubMed] [CrossRef]
102. Folders J,, Tommassen J,, van Loon LC,, Bitter W . 2000. Identification of a chitin-binding protein secreted by Pseudomonas aeruginosa . J Bacteriol 182 : 12571263.[PubMed] [CrossRef]
103. Folders J,, Algra J,, Roelofs MS,, van Loon LC,, Tommassen J,, Bitter W . 2001. Characterization of Pseudomonas aeruginosa chitinase, a gradually secreted protein. J Bacteriol 183 : 70447052.[PubMed] [CrossRef]
104. Korgaonkar A,, Trivedi U,, Rumbaugh KP,, Whiteley M . 2013. Community surveillance enhances Pseudomonas aeruginosa virulence during polymicrobial infection. Proc Natl Acad Sci USA 110 : 10591064.[PubMed] [CrossRef]
105. Ovchinnikova ES,, Krom BP,, Harapanahalli AK,, Busscher HJ,, van der Mei HC . 2013. Surface thermodynamic and adhesion force evaluation of the role of chitin-binding protein in the physical interaction between Pseudomonas aeruginosa and Candida albicans . Langmuir 29 : 48234829.[PubMed] [CrossRef]
106. Gallagher LA,, McKnight SL,, Kuznetsova MS,, Pesci EC,, Manoil C . 2002. Functions required for extracellular quinolone signaling by Pseudomonas aeruginosa . J Bacteriol 184 : 64726480.[PubMed] [CrossRef]
107. Ran H,, Hassett DJ,, Lau GW . 2003. Human targets of Pseudomonas aeruginosa pyocyanin. Proc Natl Acad Sci USA 100 : 1431514320.[PubMed] [CrossRef]
108. Britigan BE,, Roeder TL,, Rasmussen GT,, Shasby DM,, McCormick ML,, Cox CD . 1992. Interaction of the Pseudomonas aeruginosa secretory products pyocyanin and pyochelin generates hydroxyl radical and causes synergistic damage to endothelial cells. Implications for Pseudomonas-associated tissue injury. J Clin Invest 90 : 21872196.[PubMed] [CrossRef]
109. Denning GM,, Railsback MA,, Rasmussen GT,, Cox CD,, Britigan BE . 1998. Pseudomonas pyocyanine alters calcium signaling in human airway epithelial cells. Am J Physiol 274 : L893L900.[PubMed]
110. Allen L,, Dockrell DH,, Pattery T,, Lee DG,, Cornelis P,, Hellewell PG,, Whyte MK . 2005. Pyocyanin production by Pseudomonas aeruginosa induces neutrophil apoptosis and impairs neutrophil-mediated host defenses in vivo. J Immunol 174 : 36433649.[PubMed] [CrossRef]
111. Hunter RC,, Klepac-Ceraj V,, Lorenzi MM,, Grotzinger H,, Martin TR,, Newman DK . 2012. Phenazine content in the cystic fibrosis respiratory tract negatively correlates with lung function and microbial complexity. Am J Respir Cell Mol Biol 47 : 738745.[PubMed] [CrossRef]
112. Dietrich LE,, Price-Whelan A,, Petersen A,, Whiteley M,, Newman DK . 2006. The phenazine pyocyanin is a terminal signalling factor in the quorum sensing network of Pseudomonas aeruginosa . Mol Microbiol 61 : 13081321.[PubMed] [CrossRef]
113. Huse H,, Whiteley M . 2011. 4-Quinolones: smart phones of the microbial world. Chem Rev 111 : 152159.[PubMed] [CrossRef]
114. Lepine F,, Milot S,, Deziel E,, He J,, Rahme LG . 2004. Electrospray/mass spectrometric identification and analysis of 4-hydroxy-2-alkylquinolines (HAQs) produced by Pseudomonas aeruginosa . J Am Soc Mass Spectrom 15 : 862869.[PubMed] [CrossRef]
115. Haussler S,, Becker T . 2008. The pseudomonas quinolone signal (PQS) balances life and death in Pseudomonas aeruginosa populations. PLoS Pathog 4 : e1000166. [PubMed] [CrossRef]
116. Gallagher LA,, Manoil C . 2001. Pseudomonas aeruginosa PAO1 kills Caenorhabditis elegans by cyanide poisoning. J Bacteriol 183 : 62076214.[PubMed] [CrossRef]
117. Goldfarb WB,, Margraf H . 1964. Cyanide Production by Pseudomonas aeruginosa . Surg Forum 15 : 467469.[PubMed]
118. Anderson RD,, Roddam LF,, Bettiol S,, Sanderson K,, Reid DW . 2010. Biosignificance of bacterial cyanogenesis in the CF lung. J Cyst Fibros 9 : 158164.[PubMed] [CrossRef]
119. Pessi G,, Haas D . 2000. Transcriptional control of the hydrogen cyanide biosynthetic genes hcnABC by the anaerobic regulator ANR and the quorum-sensing regulators LasR and RhlR in Pseudomonas aeruginosa . J Bacteriol 182 : 69406949.[PubMed] [CrossRef]
120. Emerson J,, Rosenfeld M,, McNamara S,, Ramsey B,, Gibson RL . 2002. Pseudomonas aeruginosa and other predictors of mortality and morbidity in young children with cystic fibrosis. Pediatr Pulmonol 34 : 91100.[PubMed] [CrossRef]
121. Hancock RE,, Mutharia LM,, Chan L,, Darveau RP,, Speert DP,, Pier GB . 1983. Pseudomonas aeruginosa isolates from patients with cystic fibrosis: a class of serum-sensitive, nontypable strains deficient in lipopolysaccharide O side chains. Infect Immun 42 : 170177.[PubMed]
122. Huse HK,, Kwon T,, Zlosnik JE,, Speert DP,, Marcotte EM,, Whiteley M . 2010. Parallel evolution in Pseudomonas aeruginosa over 39,000 generations in vivo. MBio 1(4): e00199–10.[PubMed] [CrossRef]
123. Luzar MA,, Montie TC . 1985. Avirulence and altered physiological properties of cystic fibrosis strains of Pseudomonas aeruginosa . Infect Immun 50 : 572576.[PubMed]
124. Mahenthiralingam E,, Campbell ME,, Speert DP . 1994. Nonmotility and phagocytic resistance of Pseudomonas aeruginosa isolates from chronically colonized patients with cystic fibrosis. Infect Immun 62 : 596605.[PubMed]
125. Wahba AH,, Darrell JH . 1965. The Identification of Atypical Strains of Pseudomonas aeruginosa . J Gen Microbiol 38 : 329342.[PubMed] [CrossRef]
126. Wilder CN,, Allada G,, Schuster M . 2009. Instantaneous within-patient diversity of Pseudomonas aeruginosa quorum-sensing populations from cystic fibrosis lung infections. Infect Immun 77 : 56315639.[PubMed] [CrossRef]
127. Ernst RK,, Yi EC,, Guo L,, Lim KB,, Burns JL,, Hackett M,, Miller SI . 1999. Specific lipopolysaccharide found in cystic fibrosis airway Pseudomonas aeruginosa . Science 286 : 15611565.[PubMed] [CrossRef]
128. Smith EE,, Buckley DG,, Wu Z,, Saenphimmachak C,, Hoffman LR,, D’Argenio DA,, Miller SI,, Ramsey BW,, Speert DP,, Moskowitz SM,, Burns JL,, Kaul R,, Olson MV . 2006. Genetic adaptation by Pseudomonas aeruginosa to the airways of cystic fibrosis patients. Proc Natl Acad Sci USA 103 : 84878492.[PubMed] [CrossRef]
129. Rau MH,, Hansen SK,, Johansen HK,, Thomsen LE,, Workman CT,, Nielsen KF,, Jelsbak L,, Hoiby N,, Yang L,, Molin S . 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 : 16431658.[PubMed]
130. Folkesson A,, Jelsbak L,, Yang L,, Johansen HK,, Ciofu O,, Hoiby N,, Molin S . 2012. Adaptation of Pseudomonas aeruginosa to the cystic fibrosis airway: an evolutionary perspective. Nat Rev Microbiol 10 : 841851.[PubMed] [CrossRef]
131. Boman HG,, Nilsson I,, Rasmuson B . 1972. Inducible antibacterial defence system in Drosophila . Nature 237 : 232235.[PubMed] [CrossRef]
132. Elrod RP,, Braun AC . 1942. Pseudomonas aeruginosa: Its Role as a Plant Pathogen. J Bacteriol 44 : 633645.[PubMed]
133. Jander G,, Rahme LG,, Ausubel FM . 2000. Positive correlation between virulence of Pseudomonas aeruginosa mutants in mice and insects. J Bacteriol 182 : 38433845.[PubMed] [CrossRef]
134. Mahajan-Miklos S,, Tan MW,, Rahme LG,, Ausubel FM . 1999. Molecular mechanisms of bacterial virulence elucidated using a Pseudomonas aeruginosa-Caenorhabditis elegans pathogenesis model. Cell 96 : 4756.[PubMed] [CrossRef]
135. Phennicie RT,, Sullivan MJ,, Singer JT,, Yoder JA,, Kim CH . 2010. Specific resistance to Pseudomonas aeruginosa infection in zebrafish is mediated by the cystic fibrosis transmembrane conductance regulator. Infect Immun 78 : 45424550.[PubMed] [CrossRef]
136. Tan MW,, Mahajan-Miklos S,, Ausubel FM . 1999. Killing of Caenorhabditis elegans by Pseudomonas aeruginosa used to model mammalian bacterial pathogenesis. Proc Natl Acad Sci USA 96 : 715720.[PubMed] [CrossRef]
137. Tan MW,, Rahme LG,, Sternberg JA,, Tompkins RG,, Ausubel FM . 1999. Pseudomonas aeruginosa killing of Caenorhabditis elegans used to identify P. aeruginosa virulence factors. Proc Natl Acad Sci USA 96 : 24082413.[PubMed] [CrossRef]
138. Wilke M,, Buijs-Offerman RM,, Aarbiou J,, Colledge WH,, Sheppard DN,, Touqui L,, Bot A,, Jorna H,, de Jonge HR,, Scholte BJ . 2011. Mouse models of cystic fibrosis: phenotypic analysis and research applications. J Cyst Fibros 10(Suppl 2): S152S171.[PubMed] [CrossRef]
139. Clarke LL,, Grubb BR,, Gabriel SE,, Smithies O,, Koller BH,, Boucher RC . 1992. Defective epithelial chloride transport in a gene-targeted mouse model of cystic fibrosis. Science 257 : 11251128.[PubMed] [CrossRef]
140. Colledge WH,, Ratcliff R,, Foster D,, Williamson R,, Evans MJ . 1992. Cystic fibrosis mouse with intestinal obstruction. Lancet 340 : 680. [PubMed] [CrossRef]
141. Dorin JR,, Dickinson P,, Alton EW,, Smith SN,, Geddes DM,, Stevenson BJ,, Kimber WL,, Fleming S,, Clarke AR,, Hooper ML , , et al . 1992. Cystic fibrosis in the mouse by targeted insertional mutagenesis. Nature 359 : 211215.[PubMed] [CrossRef]
142. Snouwaert JN,, Brigman KK,, Latour AM,, Malouf NN,, Boucher RC,, Smithies O,, Koller BH . 1992. An animal model for cystic fibrosis made by gene targeting. Science 257 : 10831088.[PubMed] [CrossRef]
143. Colledge WH,, Abella BS,, Southern KW,, Ratcliff R,, Jiang C,, Cheng SH,, MacVinish LJ,, Anderson JR,, Cuthbert AW,, Evans MJ . 1995. Generation and characterization of a delta F508 cystic fibrosis mouse model. Nat Genet 10 : 445452.[PubMed] [CrossRef]
144. Kent G,, Iles R,, Bear CE,, Huan LJ,, Griesenbach U,, McKerlie C,, Frndova H,, Ackerley C,, Gosselin D,, Radzioch D,, O’Brodovich H,, Tsui LC,, Buchwald M,, Tanswell AK . 1997. Lung disease in mice with cystic fibrosis. J Clin Invest 100 : 30603069.[PubMed] [CrossRef]
145. Yu H,, Hanes M,, Chrisp CE,, Boucher JC,, Deretic V . 1998. Microbial pathogenesis in cystic fibrosis: pulmonary clearance of mucoid Pseudomonas aeruginosa and inflammation in a mouse model of repeated respiratory challenge. Infect Immun 66 : 280288.[PubMed]
146. Gosselin D,, Stevenson MM,, Cowley EA,, Griesenbach U,, Eidelman DH,, Boule M,, Tam MF,, Kent G,, Skamene E,, Tsui LC,, Radzioch D . 1998. Impaired ability of Cftr knockout mice to control lung infection with Pseudomonas aeruginosa . Am J Respir Crit Care Med 157 : 12531262.[PubMed] [CrossRef]
147. Heeckeren A,, Walenga R,, Konstan MW,, Bonfield T,, Davis PB,, Ferkol T . 1997. Excessive inflammatory response of cystic fibrosis mice to bronchopulmonary infection with Pseudomonas aeruginosa . J Clin Invest 100 : 28102815.[PubMed] [CrossRef]
148. Coleman FT,, Mueschenborn S,, Meluleni G,, Ray C,, Carey VJ,, Vargas SO,, Cannon CL,, Ausubel FM,, Pier GB . 2003. Hypersusceptibility of cystic fibrosis mice to chronic Pseudomonas aeruginosa oropharyngeal colonization and lung infection. Proc Natl Acad Sci USA 100 : 19491954.[PubMed] [CrossRef]
149. Hoffmann N,, Rasmussen TB,, Jensen PO,, Stub C,, Hentzer M,, Molin S,, Ciofu O,, Givskov M,, Johansen HK,, Hoiby N . 2005. Novel mouse model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis. Infect Immun 73 : 25042514.[PubMed] [CrossRef]
150. Hodges CA,, Cotton CU,, Palmert MR,, Drumm ML . 2008. Generation of a conditional null allele for Cftr in mice. Genesis 46 : 546552.[PubMed] [CrossRef]
151. Keiser NW,, Engelhardt JF . 2011. New animal models of cystic fibrosis: what are they teaching us? Curr Opin Pulm Med 17 : 478483.[PubMed] [CrossRef]
152. Bonfield TL,, Hodges CA,, Cotton CU,, Drumm ML . 2012. Absence of the cystic fibrosis transmembrane regulator (Cftr) from myeloid-derived cells slows resolution of inflammation and infection. J Leukoc Biol 92 : 11111122.[PubMed] [CrossRef]
153. Stoltz DA,, Meyerholz DK,, Pezzulo AA,, Ramachandran S,, Rogan MP,, Davis GJ,, Hanfland RA,, Wohlford-Lenane C,, Dohrn CL,, Bartlett JA,, Nelson GAt,, Chang EH,, Taft PJ,, Ludwig PS,, Estin M,, Hornick EE,, Launspach JL,, Samuel M,, Rokhlina T,, Karp PH,, Ostedgaard LS,, Uc A,, Starner TD,, Horswill AR,, Brogden KA,, Prather RS,, Richter SS,, Shilyansky J,, McCray PB Jr,, Zabner J,, Welsh MJ . 2010. Cystic fibrosis pigs develop lung disease and exhibit defective bacterial eradication at birth. Sci Transl Med 2 : 29ra31. [PubMed] [CrossRef]
154. Rogers CS,, Stoltz DA,, Meyerholz DK,, Ostedgaard LS,, Rokhlina T,, Taft PJ,, Rogan MP,, Pezzulo AA,, Karp PH,, Itani OA,, Kabel AC,, Wohlford-Lenane CL,, Davis GJ,, Hanfland RA,, Smith TL,, Samuel M,, Wax D,, Murphy CN,, Rieke A,, Whitworth K,, Uc A,, Starner TD,, Brogden KA,, Shilyansky J,, McCray PB Jr,, Zabner J,, Prather RS,, Welsh MJ . 2008. Disruption of the CFTR gene produces a model of cystic fibrosis in newborn pigs. Science 321 : 18371841.[PubMed] [CrossRef]
155. Pezzulo AA,, Tang XX,, Hoegger MJ,, Alaiwa MH,, Ramachandran S,, Moninger TO,, Karp PH,, Wohlford-Lenane CL,, Haagsman HP,, van Eijk M,, Banfi B,, Horswill AR,, Stoltz DA,, McCray PB Jr,, Welsh MJ,, Zabner J . 2012. Reduced airway surface pH impairs bacterial killing in the porcine cystic fibrosis lung. Nature 487 : 109113.[PubMed] [CrossRef]
156. Ostedgaard LS,, Meyerholz DK,, Chen JH,, Pezzulo AA,, Karp PH,, Rokhlina T,, Ernst SE,, Hanfland RA,, Reznikov LR,, Ludwig PS,, Rogan MP,, Davis GJ,, Dohrn CL,, Wohlford-Lenane C,, Taft PJ,, Rector MV,, Hornick E,, Nassar BS,, Samuel M,, Zhang Y,, Richter SS,, Uc A,, Shilyansky J,, Prather RS,, McCray PB Jr,, Zabner J,, Welsh MJ,, Stoltz DA . 2011. The DeltaF508 mutation causes CFTR misprocessing and cystic fibrosis-like disease in pigs. Sci Transl Med 3 : 74ra24. [PubMed] [CrossRef]
157. Sun X,, Sui H,, Fisher JT,, Yan Z,, Liu X,, Cho HJ,, Joo NS,, Zhang Y,, Zhou W,, Yi Y,, Kinyon JM,, Lei-Butters DC,, Griffin MA,, Naumann P,, Luo M,, Ascher J,, Wang K,, Frana T,, Wine JJ,, Meyerholz DK,, Engelhardt JF . 2010. Disease phenotype of a ferret CFTR-knockout model of cystic fibrosis. J Clin Invest 120 : 31493160.[PubMed] [CrossRef]
158. Fisher JT,, Liu X,, Yan Z,, Luo M,, Zhang Y,, Zhou W,, Lee BJ,, Song Y,, Guo C,, Wang Y,, Lukacs GL,, Engelhardt JF . 2012. Comparative processing and function of human and ferret cystic fibrosis transmembrane conductance regulator. J Biol Chem 287 : 2167321685.[PubMed] [CrossRef]
159. Ohman DE,, Chakrabarty AM . 1982. Utilization of human respiratory secretions by mucoid Pseudomonas aeruginosa of cystic fibrosis origin. Infect Immun 37 : 662669.[PubMed]
160. Palmer KL,, Brown SA,, Whiteley M . 2007. Membrane-bound nitrate reductase is required for anaerobic growth in cystic fibrosis sputum. J Bacteriol 189 : 44494455.[PubMed] [CrossRef]
161. Schobert M,, Tielen P . 2010. Contribution of oxygen-limiting conditions to persistent infection of Pseudomonas aeruginosa . Future Microbiol 5 : 603621.[PubMed] [CrossRef]
162. Su S,, Hassett DJ . 2012. Anaerobic Pseudomonas aeruginosa and other obligately anaerobic bacterial biofilms growing in the thick airway mucus of chronically infected cystic fibrosis patients: an emerging paradigm or “Old Hat”? Expert Opin Ther Targets 16 : 859873.[PubMed] [CrossRef]
163. Ghani M,, Soothill JS . 1997. Ceftazidime, gentamicin, and rifampicin, in combination, kill biofilms of mucoid Pseudomonas aeruginosa . Can J Microbiol 43 : 9991004.[PubMed] [CrossRef]
164. Sriramulu DD,, Lunsdorf H,, Lam JS,, Romling U . 2005. Microcolony formation: a novel biofilm model of Pseudomonas aeruginosa for the cystic fibrosis lung. J Med Microbiol 54 : 667676.[PubMed] [CrossRef]
165. Fung C,, Naughton S,, Turnbull L,, Tingpej P,, Rose B,, Arthur J,, Hu H,, Harmer C,, Harbour C,, Hassett DJ,, Whitchurch CB,, Manos J . 2010. Gene expression of Pseudomonas aeruginosa in a mucin-containing synthetic growth medium mimicking cystic fibrosis lung sputum. J Med Microbiol 59 : 10891100.[PubMed] [CrossRef]
166. Haley CL,, Colmer-Hamood JA,, Hamood AN . 2012. Characterization of biofilm-like structures formed by Pseudomonas aeruginosa in a synthetic mucus medium. BMC Microbiol 12 : 181. [PubMed] [CrossRef]
167. Poole K,, McKay GA . 2003. Iron acquisition and its control in Pseudomonas aeruginosa: many roads lead to Rome. Front Biosci 8 : d661d686.[PubMed] [CrossRef]
168. Vasil ML,, Ochsner UA . 1999. The response of Pseudomonas aeruginosa to iron: genetics, biochemistry and virulence. Mol Microbiol 34 : 399413.[PubMed] [CrossRef]
169. Martin LW,, Reid DW,, Sharples KJ,, Lamont IL . 2011. Pseudomonas siderophores in the sputum of patients with cystic fibrosis. Biometals 24 : 10591067.[PubMed] [CrossRef]
170. Mashburn LM,, Jett AM,, Akins DR,, Whiteley M . 2005. Staphylococcus aureus serves as an iron source for Pseudomonas aeruginosa during in vivo coculture. J Bacteriol 187 : 554566.[PubMed] [CrossRef]
171. Chen X,, Stewart PS . 2002. Role of electrostatic interactions in cohesion of bacterial biofilms. Appl Microbiol Biotechnol 59 : 718720.[PubMed] [CrossRef]
172. Koley D,, Ramsey MM,, Bard AJ,, Whiteley M . 2011. Discovery of a biofilm electrocline using real-time 3D metabolite analysis. Proc Natl Acad Sci USA 108 : 1999620001.[PubMed] [CrossRef]
173. Hunter RC,, Asfour F,, Dingemans J,, Osuna BL,, Samad T,, Malfroot A,, Cornelis P,, Newman DK . 2013. Ferrous iron is a significant component of bioavailable iron in cystic fibrosis airways. MBio 4(4): e00557–13.[PubMed] [CrossRef]
174. Hare NJ,, Soe CZ,, Rose B,, Harbour C,, Codd R,, Manos J,, Cordwell SJ . 2012. Proteomics of Pseudomonas aeruginosa Australian epidemic strain 1 (AES-1) cultured under conditions mimicking the cystic fibrosis lung reveals increased iron acquisition via the siderophore pyochelin. J Proteome Res 11 : 776795.[PubMed] [CrossRef]
175. Henke MO,, John G,, Rheineck C,, Chillappagari S,, Naehrlich L,, Rubin BK . 2011. Serine proteases degrade airway mucins in cystic fibrosis. Infect Immun 79 : 34383444.[PubMed] [CrossRef]
176. Aristoteli LP,, Willcox MD . 2003. Mucin degradation mechanisms by distinct Pseudomonas aeruginosa isolates in vitro. Infect Immun 71 : 55655575.[CrossRef]
177. Ramphal R,, Pyle M . 1983. Evidence for mucins and sialic acid as receptors for Pseudomonas aeruginosa in the lower respiratory tract. Infect Immun 41 : 339344.[PubMed]
178. Scharfman A,, Degroote S,, Beau J,, Lamblin G,, Roussel P,, Mazurier J . 1999. Pseudomonas aeruginosa binds to neoglycoconjugates bearing mucin carbohydrate determinants and predominantly to sialyl-Lewis x conjugates. Glycobiology 9 : 757764.[PubMed] [CrossRef]
179. Vishwanath S,, Ramphal R . 1984. Adherence of Pseudomonas aeruginosa to human tracheobronchial mucin. Infect Immun 45 : 197202.[PubMed]
180. Sajjan U,, Reisman J,, Doig P,, Irvin RT,, Forstner G,, Forstner J . 1992. Binding of nonmucoid Pseudomonas aeruginosa to normal human intestinal mucin and respiratory mucin from patients with cystic fibrosis. J Clin Invest 89 : 657665.[PubMed] [CrossRef]
181. Kubiet M,, Ramphal R . 1995. Adhesion of nontypeable Haemophilus influenzae from blood and sputum to human tracheobronchial mucins and lactoferrin. Infect Immun 63 : 899902.[PubMed]
182. Reddy MS,, Bernstein JM,, Murphy TF,, Faden HS . 1996. Binding between outer membrane proteins of nontypeable Haemophilus influenzae and human nasopharyngeal mucin. Infect Immun 64 : 14771479.[PubMed]
183. Sajjan SU,, Forstner JF . 1992. Identification of the mucin-binding adhesin of Pseudomonas cepacia isolated from patients with cystic fibrosis. Infect Immun 60 : 14341440.[PubMed]
184. Sajjan US,, Corey M,, Karmali MA,, Forstner JF . 1992. Binding of Pseudomonas cepacia to normal human intestinal mucin and respiratory mucin from patients with cystic fibrosis. J Clin Invest 89 : 648656.[PubMed] [CrossRef]
185. Shuter J,, Hatcher VB,, Lowy FD . 1996. Staphylococcus aureus binding to human nasal mucin. Infect Immun 64 : 310318.[PubMed]
186. Ramphal R,, Houdret N,, Koo L,, Lamblin G,, Roussel P . 1989. Differences in adhesion of Pseudomonas aeruginosa to mucin glycopeptides from sputa of patients with cystic fibrosis and chronic bronchitis. Infect Immun 57 : 30663071.[PubMed]
187. Landry RM,, An D,, Hupp JT,, Singh PK,, Parsek MR . 2006. Mucin-Pseudomonas aeruginosa interactions promote biofilm formation and antibiotic resistance. Mol Microbiol 59 : 142151.[PubMed] [CrossRef]
188. Yeung AT,, Parayno A,, Hancock RE . 2012. Mucin promotes rapid surface motility in Pseudomonas aeruginosa . M Bio 3(3): e00073–12.[PubMed] [CrossRef]
189. Caldara M,, Friedlander RS,, Kavanaugh NL,, Aizenberg J,, Foster KR,, Ribbeck K . 2012. Mucin biopolymers prevent bacterial aggregation by retaining cells in the free-swimming state. Curr Biol 22 : 23252330.[PubMed] [CrossRef]
190. Son MS,, Matthews WJ Jr,, Kang Y,, Nguyen DT,, Hoang TT . 2007. In vivo evidence of Pseudomonas aeruginosa nutrient acquisition and pathogenesis in the lungs of cystic fibrosis patients. Infect Immun 75 : 53135324.[PubMed] [CrossRef]
191. Storey DG,, Ujack EE,, Rabin HR . 1992. Population transcript accumulation of Pseudomonas aeruginosa exotoxin A and elastase in sputa from patients with cystic fibrosis. Infect Immun 60 : 46874694.[PubMed]
192. Kang Y,, Zarzycki-Siek J,, Walton CB,, Norris MH,, Hoang TT . 2010. Multiple FadD acyl-CoA synthetases contribute to differential fatty acid degradation and virulence in Pseudomonas aeruginosa . PLoS One 5 : e13557. [PubMed] [CrossRef]
193. Wargo MJ,, Gross MJ,, Rajamani S,, Allard JL,, Lundblad LK,, Allen GB,, Vasil ML,, Leclair LW,, Hogan DA . 2011. Hemolytic phospholipase C inhibition protects lung function during Pseudomonas aeruginosa infection. Am J Respir Crit Care Med 184 : 345354.