Top

Clinical Reviews in Allergy & Immunology

Published in:

Open Access 01-12-2008

P. aeruginosa Biofilms in CF Infection

Authors: Victoria E. Wagner, Barbara H. Iglewski

Published in: Clinical Reviews in Allergy & Immunology | Issue 3/2008

Abstract

Pseudomonas aeruginosa is an opportunistic pathogen of immunocompromised hosts. In cystic fibrosis (CF), P. aeruginosa causes acute and chronic lung infections that result in significant morbidity and mortality. P. aeruginosa possesses several traits that contribute to its ability to colonize and persist in acute and chronic infections. These include high resistance to antimicrobials, ability to form biofilms, plethora of virulence products, and metabolic versatility. In P. aeruginosa, a cell-to-cell communication process termed quorum sensing (QS) regulates many of these factors that contribute to its pathogenesis. Recent evidence suggests that the CF lung environment presents a specialized niche for P. aeruginosa. The relationship of P. aeruginosa QS, biofilm formation, and the CF lung environment is discussed.

Ikeno T et al (2007) Small and rough colony Pseudomonas aeruginosa with elevated biofilm formation ability isolated in hospitalized patients. Microbiol Immunol 51(10):929–938PubMed

Whiteley M, Greenberg EP (2001) Promoter specificity elements in Pseudomonas aeruginosa quorum-sensing-controlled genes. J Bacteriol 183(19):5529–5534PubMedCrossRef

Pesci EC, Iglewski BH (1997) The chain of command in Pseudomonas quorum sensing. Trends Microbiol 5(4):132–134 discussion 134–135PubMedCrossRef

de Kievit TR et al (2002) Role of the Pseudomonas aeruginosa las and rhl quorum-sensing systems in rhlI regulation. FEMS Microbiol Lett 212(1):101–106PubMed

Pesci E, Iglewski B (1999) Quorum sensing in Pseudomonas aeruginosa, in cell–cell signaling in bacteria. American Society for Microbiology, Washington DC, pp 147–155

McKnight SL, Iglewski BH, Pesci EC (2000) The Pseudomonas quinolone signal regulates rhl quorum sensing in Pseudomonas aeruginosa. J Bacteriol 182(10):2702–2708PubMedCrossRef

Hentzer M et al (2003) Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors. Embo J 22(15):3803–3815PubMedCrossRef

Schuster M et al (2003) Identification, timing, and signal specificity of Pseudomonas aeruginosa quorum-controlled genes: a transcriptome analysis. J Bacteriol 185(7):2066–2079PubMedCrossRef

Wagner VE et al (2003) Microarray analysis of Pseudomonas aeruginosa quorum-sensing regulons: effects of growth phase and environment. J Bacteriol 185(7):2080–2095PubMedCrossRef

10.

Parsek MR, Greenberg EP (2005) Sociomicrobiology: the connections between quorum sensing and biofilms. Trends Microbiol 13(1):27–33PubMedCrossRef

11.

Costerton JW, Stewart PS (2001) Battling biofilms. Sci Am 285(1):74–81PubMedCrossRef

12.

Costerton J, Stewart P, Greenberg E (1999) Bacterial biofilms: a common cause of persistent infections. Science 284:1318–1322PubMedCrossRef

13.

Govan JR, Deretic V (1996) Microbial pathogenesis in cystic fibrosis: mucoid Pseudomonas aeruginosa and Burkholderia cepacia. Microbiol Rev 60(3):539–574PubMed

14.

Donlan RM, Costerton JW (2002) Biofilms: survival mechanisms of clinically relevant microorganisms. Clin Microbiol Rev 15(2):167–193PubMedCrossRef

15.

Costerton JW (2002) Anaerobic biofilm infections in cystic fibrosis. Mol Cell 10(4):699–700PubMedCrossRef

16.

Gomez MI, Prince A (2007) Opportunistic infections in lung disease: Pseudomonas infections in cystic fibrosis. Curr Opin Pharmacol 7(3):244–251PubMedCrossRef

17.

Hentzer M, Eberl L, Givskov M (2005) Transcriptome analysis of Pseudomonas aeruginosa biofilm development: anaerobic respiration and iron limitation. Biofilms 2:37–61CrossRef

18.

Costerton JW, Stewart PS, Greenberg EP (1999) Bacterial biofilms: a common cause of persistent infections. Science 284(5418):1318–1322PubMedCrossRef

19.

Sauer K et al (2002) Pseudomonas aeruginosa displays multiple phenotypes during development as a biofilm. J Bacteriol 184(4):1140–1154PubMedCrossRef

20.

Xu KD et al (1998) Spatial physiological heterogeneity in Pseudomonas aeruginosa biofilm is determined by oxygen availability. Appl Environ Microbiol 64(10):4035–4039PubMed

21.

Davies DG et al (1998) The involvement of cell-to-cell signals in the development of a bacterial biofilm. Science 280(5361):295–298PubMedCrossRef

22.

Bjarnsholt T et al (2005) Pseudomonas aeruginosa tolerance to tobramycin, hydrogen peroxide and polymorphonuclear leukocytes is quorum-sensing dependent. Microbiology 151(Pt 2):373–383PubMedCrossRef

23.

Hassett DJ et al (1999) Quorum sensing in Pseudomonas aeruginosa controls expression of catalase and superoxide dismutase genes and mediates biofilm susceptibility to hydrogen peroxide. Mol Microbiol 34(5):1082–1093PubMedCrossRef

24.

Klausen M et al (2003) Biofilm formation by Pseudomonas aeruginosa wild type, flagella and type IV pili mutants. Mol Microbiol 48(6):1511–1524PubMedCrossRef

25.

Klausen M et al (2003) Involvement of bacterial migration in the development of complex multicellular structures in Pseudomonas aeruginosa biofilms. Mol Microbiol 50(1):61–68PubMedCrossRef

26.

O’Toole G, Kolter R (1998) Flagellar and twitching motility are necessary for Pseudomonas aeruginosa biofilm development. Mol Microbiol 30(2):295–304PubMedCrossRef

27.

Sonawane A, Jyot J, Ramphal R (2006) Pseudomonas aeruginosa LecB is involved in pilus biogenesis and protease IV activity but not in adhesion to respiratory mucins. Infect Immun 74(12):7035–7039PubMedCrossRef

28.

Tielker D et al (2005) Pseudomonas aeruginosa lectin LecB is located in the outer membrane and is involved in biofilm formation. Microbiology 151(Pt 5):1313–1323PubMedCrossRef

29.

Diggle SP et al (2006) The galactophilic lectin, LecA, contributes to biofilm development in Pseudomonas aeruginosa. Environ Microbiol 8(6):1095–1104PubMedCrossRef

30.

Boteva RN, Bogoeva VP, Stoitsova SR (2005) PA-I lectin from Pseudomonas aeruginosa binds acyl homoserine lactones. Biochim Biophys Acta 1747(2):143–149PubMed

31.

Winzer K et al (2000) The Pseudomonas aeruginosa lectins PA-IL and PA-IIL are controlled by quorum sensing and by RpoS. J Bacteriol 182(22):6401–6411PubMedCrossRef

32.

Pedersen SS (1992) Lung infection with alginate-producing, mucoid Pseudomonas aeruginosa in cystic fibrosis. Acta Pathol Microbiol Immunol Scand Suppl 28:1–79

33.

Pedersen SS et al (1992) Role of alginate in infection with mucoid Pseudomonas aeruginosa in cystic fibrosis. Thorax 47(1):6–13PubMedCrossRef

34.

Hentzer M et al (2001) Alginate overproduction affects Pseudomonas aeruginosa biofilm structure and function. J Bacteriol 183(18):5395–5401PubMedCrossRef

35.

Ramsey DM, Wozniak DJ (2005) Understanding the control of Pseudomonas aeruginosa alginate synthesis and the prospects for management of chronic infections in cystic fibrosis. Mol Microbiol 56(2):309–322PubMedCrossRef

36.

Ryder C, Byrd M, Wozniak DJ (2007) Role of polysaccharides in Pseudomonas aeruginosa biofilm development. Curr Opin Microbiol 10(6):644–648PubMed

37.

Reimmann C et al (1997) The global activator GacA of Pseudomonas aeruginosa PAO positively controls the production of the autoinducer N-butyryl-homoserine lactone and the formation of the virulence factors pyocyanin, cyanide, and lipase. Mol Microbiol 24(2):309–319PubMedCrossRef

38.

Sakuragi Y, Kolter R (2007) Quorum-sensing regulation of the biofilm matrix genes (pel) of Pseudomonas aeruginosa. J Bacteriol 189(14):5383–5386PubMedCrossRef

39.

Leid JG et al (2005) The exopolysaccharide alginate protects Pseudomonas aeruginosa biofilm bacteria from IFN-gamma-mediated macrophage killing. J Immunol 175(11):7512–7518PubMed

40.

Allesen-Holm M et al (2006) A characterization of DNA release in Pseudomonas aeruginosa cultures and biofilms. Mol Microbiol 59(4):1114–1128PubMedCrossRef

41.

Whitchurch CB et al (2002) Extracellular DNA required for bacterial biofilm formation. Science 295(5559):1487PubMedCrossRef

42.

Yang L et al (2007) Effects of iron on DNA release and biofilm development by Pseudomonas aeruginosa. Microbiology 153(Pt 5):1318–1328PubMedCrossRef

43.

Whiteley M et al (2001) Gene expression in Pseudomonas aeruginosa biofilms. Nature 413(6858):860–864PubMedCrossRef

44.

Mashburn LM, Whiteley M (2005) Membrane vesicles traffic signals and facilitate group activities in a prokaryote. Nature 437(7057):422–425PubMedCrossRef

45.

Pearson JP, Pesci EC, Iglewski BH (1997) Roles of Pseudomonas aeruginosa las and rhl quorum-sensing systems in control of elastase and rhamnolipid biosynthesis genes. J Bacteriol 179(18):5756–5767PubMed

46.

Pamp SJ, Tolker-Nielsen T (2007) Multiple roles of biosurfactants in structural biofilm development by Pseudomonas aeruginosa. J Bacteriol 189(6):2531–2539PubMedCrossRef

47.

Boles BR, Thoendel M, Singh PK (2005) Rhamnolipids mediate detachment of Pseudomonas aeruginosa from biofilms. Mol Microbiol 57(5):1210–1223PubMedCrossRef

48.

Davey ME, Caiazza NC, O’Toole GA (2003) Rhamnolipid surfactant production affects biofilm architecture in Pseudomonas aeruginosa PAO1. J Bacteriol 185(3):1027–1036PubMedCrossRef

49.

Lequette Y, Greenberg EP (2005) Timing and localization of rhamnolipid synthesis gene expression in Pseudomonas aeruginosa biofilms. J Bacteriol 187(1):37–44PubMedCrossRef

50.

Kirov SM, Webb JS, Kjelleberg S (2005) Clinical significance of seeding dispersal in biofilms. Microbiology 151(Pt 11):3452–3453 discussion 3453PubMedCrossRef

51.

Kirov SM et al (2007) Biofilm differentiation and dispersal in mucoid Pseudomonas aeruginosa isolates from patients with cystic fibrosis. Microbiology 153(Pt 10):3264–3274PubMedCrossRef

52.

Morici LA et al (2007) Pseudomonas aeruginosa AlgR represses the Rhl quorum-sensing system in a biofilm-specific manner. J Bacteriol 189(21):7752–7764PubMedCrossRef

53.

Whitchurch CB et al (2002) Phosphorylation of the Pseudomonas aeruginosa response regulator AlgR is essential for type IV fimbria-mediated twitching motility. J Bacteriol 184(16):4544–4554PubMedCrossRef

54.

Parkins MD, Ceri H, Storey DG (2001) Pseudomonas aeruginosa GacA, a factor in multihost virulence, is also essential for biofilm formation. Mol Microbiol 40(5):1215–1226PubMedCrossRef

55.

O’Toole GA et al (2000) The global carbon metabolism regulator Crc is a component of a signal transduction pathway required for biofilm development by Pseudomonas aeruginosa. J Bacteriol 182(2):425–431PubMedCrossRef

56.

Heydorn A et al (2002) Statistical analysis of Pseudomonas aeruginosa biofilm development: impact of mutations in genes involved in twitching motility, cell-to-cell signaling, and stationary-phase sigma factor expression. Appl Environ Microbiol 68(4):2008–2017PubMedCrossRef

57.

Goodman AL et al (2004) A signaling network reciprocally regulates genes associated with acute infection and chronic persistence in Pseudomonas aeruginosa. Dev Cell 7(5):745–754PubMedCrossRef

58.

Schuster M et al (2004) The Pseudomonas aeruginosa RpoS regulon and its relationship to quorum sensing. Mol Microbiol 51(4):973–985PubMedCrossRef

59.

Kuchma SL, Connolly JP, O’Toole GA (2005) A three-component regulatory system regulates biofilm maturation and type III secretion in Pseudomonas aeruginosa. J Bacteriol 187(4):1441–1454PubMedCrossRef

60.

Romling U, Gomelsky M, Galperin MY (2005) C-di-GMP: the dawning of a novel bacterial signalling system. Mol Microbiol 57(3):629–639PubMedCrossRef

61.

Romling U, Amikam D (2006) Cyclic di-GMP as a second messenger. Curr Opin Microbiol 9(2):218–228PubMedCrossRef

62.

Guvener ZT, Harwood CS (2007) Subcellular location characteristics of the Pseudomonas aeruginosa GGDEF protein, WspR, indicate that it produces cyclic-di-GMP in response to growth on surfaces. Mol Microbiol 66(6):1459–1473PubMed

63.

Hickman JW, Tifrea DF, Harwood CS (2005) A chemosensory system that regulates biofilm formation through modulation of cyclic diguanylate levels. Proc Natl Acad Sci USA 102(40):14422–14427PubMedCrossRef

64.

Kulasakara H et al (2006) Analysis of Pseudomonas aeruginosa diguanylate cyclases and phosphodiesterases reveals a role for bis-(3¢-5¢)-cyclic-GMP in virulence. Proc Natl Acad Sci USA 103(8):2839–2844PubMedCrossRef

65.

Lee VT et al (2007) A cyclic-di-GMP receptor required for bacterial exopolysaccharide production. Mol Microbiol 65(6):1474–1484PubMedCrossRef

66.

Merighi M et al (2007) The second messenger bis-(3¢-5¢)-cyclic-GMP and its PilZ domain-containing receptor Alg44 are required for alginate biosynthesis in Pseudomonas aeruginosa. Mol Microbiol 65(4):876–895PubMedCrossRef

67.

Morgan R et al (2006) BdlA, a chemotaxis regulator essential for biofilm dispersion in Pseudomonas aeruginosa. J Bacteriol 188(21):7335–7343PubMedCrossRef

68.

Branda SS et al (2005) Biofilms: the matrix revisited. Trends Microbiol 13(1):20–26PubMedCrossRef

69.

Kulasekara HD et al (2005) A novel two-component system controls the expression of Pseudomonas aeruginosa fimbrial cup genes. Mol Microbiol 55(2):368–380PubMedCrossRef

70.

Schaber JA et al (2007) Pseudomonas aeruginosa forms biofilms in acute infection independent of cell-to-cell signaling. Infect Immun 75(8):3715–3721PubMedCrossRef

71.

Rahme LG et al (1995) Common virulence factors for bacterial pathogenicity in plants and animals. Science 268(5219):1899–1902PubMedCrossRef

72.

Rumbaugh KP, Griswold JA, Hamood AN (1999) Contribution of the regulatory gene lasR to the pathogenesis of Pseudomonas aeruginosa infection of burned mice. J Burn Care Rehabil 20(1):42–49PubMed

73.

Mahajan-Miklos S, Rahme LG, Ausubel FM (2000) Elucidating the molecular mechanisms of bacterial virulence using non-mammalian hosts. Mol Microbiol 37(5):981–988PubMedCrossRef

74.

Hendrickson EL et al (2001) Differential roles of the Pseudomonas aeruginosa PA14 rpoN gene in pathogenicity in plants, nematodes, insects, and mice. J Bacteriol 183(24):7126–7134PubMedCrossRef

75.

Singh PK et al (2000) Quorum-sensing signals indicate that cystic fibrosis lungs are infected with bacterial biofilms. Nature 407(6805):762–764PubMedCrossRef

76.

Costerton JW (2002) Anaerobic biofilm infections in cystic fibrosis. Mol Cell 10(4):699–700PubMedCrossRef

77.

Thelin WR, Boucher RC (2007) The epithelium as a target for therapy in cystic fibrosis. Curr Opin Pharmacol 7(3):290–295PubMedCrossRef

78.

Hassett DJ et al (2002) Anaerobic metabolism and quorum sensing by Pseudomonas aeruginosa biofilms in chronically infected cystic fibrosis airways: rethinking antibiotic treatment strategies and drug targets. Adv Drug Deliv Rev 54(11):1425–1443PubMedCrossRef

79.

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

80.

Hass D, Gamper M, Zimmermann A (1992) Anaerobic control in Pseudomons aeruginosa. In: Galli E, Silver S, Witholt B (eds) Pseudomonas: molecular biology and biotechnology. American Society for Microbiology, Washington, DC, pp 177–187

81.

Hassett DJ (1996) Anaerobic production of alginate by Pseudomonas aeruginosa: alginate restricts diffusion of oxygen. J Bacteriol 178(24):7322–7325PubMed

82.

Linnane SJ et al (1998) Total sputum nitrate plus nitrite is raised during acute pulmonary infection in cystic fibrosis. Am J Respir Crit Care Med 158(1):207–212PubMed

83.

Grasemann H (1999) Total sputum nitrate plus nitrite is raised during acute pulmonary infection in cystic fibrosis. Am J Respir Crit Care Med 159(2):684–685PubMed

84.

Mercenier A et al (1980) Regulation of enzyme synthesis in the arginine deiminase pathway of Pseudomonas aeruginosa. J Bacteriol 144(1):159–163PubMed

85.

Vander Wauven C et al (1984) Pseudomonas aeruginosa mutants affected in anaerobic growth on arginine: evidence for a four-gene cluster encoding the arginine deiminase pathway. J Bacteriol 160(3):928–934PubMed

86.

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

87.

O’May CY, Reid DW, Kirov SM (2006) Anaerobic culture conditions favor biofilm-like phenotypes in Pseudomonas aeruginosa isolates from patients with cystic fibrosis. FEMS Immunol Med Microbiol 48(3):373–380PubMedCrossRef

88.

Govan J, Deretic V (1996) Microbial pathogenesis in cystic fibrosis: mucoid Pseudomonas aeruginosa and Burkholderia cepacia. Microbiol Rev 60(3):539–574PubMed

89.

Yoon SS et al (2002) Pseudomonas aeruginosa anaerobic respiration in biofilms: relationships to cystic fibrosis pathogenesis. Dev Cell 3(4):593–603PubMedCrossRef

90.

Barraud N et al (2006) Involvement of nitric oxide in biofilm dispersal of Pseudomonas aeruginosa. J Bacteriol 188(21):7344–7353PubMedCrossRef

91.

Yoon SS et al (2006) Anaerobic killing of mucoid Pseudomonas aeruginosa by acidified nitrite derivatives under cystic fibrosis airway conditions. J Clin Invest 116(2):436–446PubMedCrossRef

92.

Matsui H et al (2006) A physical linkage between cystic fibrosis airway surface dehydration and Pseudomonas aeruginosa biofilms. Proc Natl Acad Sci USA 103(48):18131–18136PubMedCrossRef

93.

Tang HB et al (1996) Contribution of specific Pseudomonas aeruginosa virulence factors to pathogenesis of pneumonia in a neonatal mouse model of infection. Infect Immun 64(1):37–43PubMed

94.

Rahme LG et al (1997) Use of model plant hosts to identify Pseudomonas aeruginosa virulence factors. Proc Natl Acad Sci USA 94(24):13245–13250PubMedCrossRef

95.

Preston MJ et al (1997) Contribution of proteases and LasR to the virulence of Pseudomonas aeruginosa during corneal infections. Infect Immun 65(8):3086–3090PubMed

96.

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(2):715–720PubMedCrossRef

97.

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

98.

de Kievit TR, Iglewski BH (2000) Bacterial quorum sensing in pathogenic relationships. Infect Immun 68(9):4839–4849PubMedCrossRef

99.

Plotnikova JM, Rahme LG, Ausubel FM (2000) Pathogenesis of the human opportunistic pathogen Pseudomonas aeruginosa PA14 in Arabidopsis. Plant Physiol 124(4):1766–1774PubMedCrossRef

100.

Rahme LG et al (2000) Plants and animals share functionally common bacterial virulence factors. Proc Natl Acad Sci USA 97(16):8815–8821PubMedCrossRef

101.

Jander G, Rahme LG, Ausubel FM (2000) Positive correlation between virulence of Pseudomonas aeruginosa mutants in mice and insects. J Bacteriol 182(13):3843–3845PubMedCrossRef

102.

Tang H, Kays M, Prince A (1995) Role of Pseudomonas aeruginosa pili in acute pulmonary infection. Infect Immun 63(4):1278–1285PubMed

103.

Pearson JP et al (2000) Pseudomonas aeruginosa cell-to-cell signaling is required for virulence in a model of acute pulmonary infection. Infect Immun 68(7):4331–4334PubMedCrossRef

104.

Potvin E et al (2003) In vivo functional genomics of Pseudomonas aeruginosa for high-throughput screening of new virulence factors and antibacterial targets. Environ Microbiol 5(12):1294–1308PubMedCrossRef

105.

Hoffmann N et al (2005) Novel mouse model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis. Infect Immun 73(4):2504–2514PubMedCrossRef

106.

Erickson DL et al (2002) Pseudomonas aeruginosa quorum-sensing systems may control virulence factor expression in the lungs of patients with cystic fibrosis. Infect Immun 70(4):1783–1790PubMedCrossRef

107.

Storey D et al (1998) Pseudomonas aeruginosa lasR transcription correlates with the transcription of lasA, lasB, and toxA in chronic lung infections associated with cystic fibrosis. Infect Immun 66(6):2521–2528PubMed

108.

Deretic V, Gill JF, Chakrabarty AM (1987) Gene algD coding for GDPmannose dehydrogenase is transcriptionally activated in mucoid Pseudomonas aeruginosa. J Bacteriol 169(1):351–358PubMed

109.

Collier DN et al (2002) A bacterial cell to cell signal in the lungs of cystic fibrosis patients. FEMS Microbiol Lett 215(1):41–46PubMedCrossRef

110.

Smith KM, Bu Y, Suga H (2003) Library screening for synthetic agonists and antagonists of a Pseudomonas aeruginosa autoinducer. Chem Biol 10(6):563–571PubMedCrossRef

111.

Schaber JA et al (2004) Analysis of quorum sensing-deficient clinical isolates of Pseudomonas aeruginosa. J Med Microbiol 53(Pt):841–853PubMedCrossRef

112.

Sandoz KM, Mitzimberg SM, Schuster M (2007) Social cheating in Pseudomonas aeruginosa quorum sensing. Proc Natl Acad Sci USA 104(40):15876–15881PubMedCrossRef

113.

Smith RS, Iglewski BH (2003) Pseudomonas aeruginosa quorum sensing as a potential antimicrobial target. J Clin Invest 112(10):1460–1465PubMed

Title: P. aeruginosa Biofilms in CF Infection
Authors: Victoria E. Wagner
Barbara H. Iglewski
Publication date: 01-12-2008
Publisher: Humana Press Inc
Published in: Clinical Reviews in Allergy & Immunology / Issue 3/2008
Print ISSN: 1080-0549
Electronic ISSN: 1559-0267
DOI: https://doi.org/10.1007/s12016-008-8079-9

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2008

Gene Therapy for Cystic Fibrosis

Anti-inflammatory Therapies for Cystic Fibrosis-Related Lung Disease

Diagnosis of Cystic Fibrosis

Overview of Lung Transplantation

Newborn Screening for Cystic Fibrosis

Cystic Fibrosis: Evolution from a Fatal Disease of Infancy with a Clear Phenotype to a Chronic Disease of Adulthood with Diverse Manifestations

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials