Home LiteratureArticle Details
PMID: 11514525 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Alginate overproduction affects Pseudomonas aeruginosa biofilm structure and function.

Journal of bacteriology ·Vol. 183 ·No. 18 ·2001-09-00 ·Pages 5395-401

Hentzer M, Teitzel GM, Balzer GJ, Heydorn A, Molin S, Givskov M, Parsek MR

Abstract

During the course of chronic cystic fibrosis (CF) infections, Pseudomonas aeruginosa undergoes a conversion to a mucoid phenotype, which is characterized by overproduction of the exopolysaccharide alginate. Chronic P. aeruginosa infections involve surface-attached, highly antibiotic-resistant communities of microorganisms organized in biofilms. Although biofilm formation and the conversion to mucoidy are both important aspects of CF pathogenesis, the relationship between them is at the present unclear. In this study, we report that the overproduction of alginate affects biofilm development on an abiotic surface. Biofilms formed by an alginate-overproducing strain exhibit a highly structured architecture and are significantly more resistant to the antibiotic tobramycin than a biofilm formed by an isogenic nonmucoid strain. These results suggest that an important consequence of the conversion to mucoidy is an altered biofilm architecture that shows increasing resistance to antimicrobial treatments.

MeSH Terms
Alginates/metabolism Anti-Bacterial Agents/pharmacology Biofilms/drug effects,growth & development Drug Resistance, Microbial Glucuronic Acid Hexuronic Acids Humans Pseudomonas aeruginosa/drug effects,genetics,metabolism,physiology Tobramycin/pharmacology
Chemicals
Alginates Anti-Bacterial Agents Hexuronic Acids Glucuronic Acid Tobramycin
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Hentzer M
Department of Microbiology, Technical University of Denmark, 2800 Lyngby, Denmark.
Teitzel G M
Balzer G J
Heydorn A
Molin S
Givskov M
Parsek M R
References (52)
52 references, click to expand
  1. Effect of starvation and the viable-but-nonculturable state on green fluorescent protein (GFP) fluorescence in GFP-tagged Pseudomonas fluorescens A506.
    Appl Environ Microbiol. 2000 Aug;66(8):3160-5 PMID: 10919764
  2. Exopolysaccharide production is required for development of Escherichia coli K-12 biofilm architecture.
    J Bacteriol. 2000 Jun;182(12):3593-6 PMID: 10852895
  3. New unstable variants of green fluorescent protein for studies of transient gene expression in bacteria.
    Appl Environ Microbiol. 1998 Jun;64(6):2240-6 PMID: 9603842
  4. Elemental composition of human airway surface fluid in healthy and diseased airways.
    Am Rev Respir Dis. 1993 Dec;148(6 Pt 1):1633-7 PMID: 8256912
  5. Dynamic interactions of biofilms of mucoid Pseudomonas aeruginosa with tobramycin and piperacillin.
    Antimicrob Agents Chemother. 1992 Jun;36(6):1208-14 PMID: 1416820
  6. Biofilm resistance to antimicrobial agents.
    Microbiology. 2000 Mar;146 ( Pt 3):547-9 PMID: 10746758
  7. Biofilm formation as microbial development.
    Annu Rev Microbiol. 2000;54:49-79 PMID: 11018124
  8. Vibrio cholerae O1 El Tor: identification of a gene cluster required for the rugose colony type, exopolysaccharide production, chlorine resistance, and biofilm formation.
    Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):4028-33 PMID: 10097157
  9. Bacterial biofilms: a common cause of persistent infections.
    Science. 1999 May 21;284(5418):1318-22 PMID: 10334980
  10. Molecular mechanisms of CFTR chloride channel dysfunction in cystic fibrosis.
    Cell. 1993 Jul 2;73(7):1251-4 PMID: 7686820
  11. Mucoid Pseudomonas aeruginosa growing in a biofilm in vitro are killed by opsonic antibodies to the mucoid exopolysaccharide capsule but not by antibodies produced during chronic lung infection in cystic fibrosis patients.
    J Immunol. 1995 Aug 15;155(4):2029-38 PMID: 7636254
  12. Genetic regulation of alginate structure in Pseudomonas aeruginosa.
    Antibiot Chemother (1971). 1989;42:56-61 PMID: 2512846
  13. Mucoid-to-nonmucoid conversion in alginate-producing Pseudomonas aeruginosa often results from spontaneous mutations in algT, encoding a putative alternate sigma factor, and shows evidence for autoregulation.
    J Bacteriol. 1994 Nov;176(21):6677-87 PMID: 7961421
  14. Characterization of a locus determining the mucoid status of Pseudomonas aeruginosa: AlgU shows sequence similarities with a Bacillus sigma factor.
    J Bacteriol. 1993 Feb;175(4):1153-64 PMID: 8432708
  15. Incidence of mucoid Pseudomonas aeruginosa from clinical sources.
    Appl Microbiol. 1969 Nov;18(5):936-7 PMID: 4984207
  16. Scavenging by alginate of free radicals released by macrophages.
    Free Radic Biol Med. 1989;6(4):347-53 PMID: 2540067
  17. [Biofilm, foreign bodies and chronic infections].
    Ugeskr Laeger. 1994 Oct 10;156(41):5998-6005 PMID: 7992437
  18. The involvement of cell-to-cell signals in the development of a bacterial biofilm.
    Science. 1998 Apr 10;280(5361):295-8 PMID: 9535661
  19. Experimental reproducibility in flow-chamber biofilms.
    Microbiology. 2000 Oct;146 ( Pt 10):2409-15 PMID: 11021917
  20. Microbial biofilms: from ecology to molecular genetics.
    Microbiol Mol Biol Rev. 2000 Dec;64(4):847-67 PMID: 11104821
  21. An immunohistological evaluation of Pseudomonas aeruginosa pulmonary infection in two patients with cystic fibrosis.
    Pediatr Res. 1987 Dec;22(6):743-7 PMID: 3431961
  22. Phase variation of slime production in Staphylococcus aureus: implications in colonization and virulence.
    Infect Immun. 1993 Nov;61(11):4857-62 PMID: 8406887
  23. Pathogenesis of cystic fibrosis.
    Lancet. 1993 Apr 24;341(8852):1065-9 PMID: 7682274
  24. Cystic fibrosis airway epithelia fail to kill bacteria because of abnormal airway surface fluid.
    Cell. 1996 Apr 19;85(2):229-36 PMID: 8612275
  25. Resistance of mucoid Pseudomonas aeruginosa to nonopsonic phagocytosis by alveolar macrophages in vitro.
    Infect Immun. 1988 Dec;56(12):3173-9 PMID: 3141284
  26. Antibiotic resistance of Pseudomonas aeruginosa colonizing a urinary catheter in vitro.
    Eur J Clin Microbiol. 1985 Apr;4(2):213-8 PMID: 3924611
  27. Production of mucoid microcolonies by Pseudomonas aeruginosa within infected lungs in cystic fibrosis.
    Infect Immun. 1980 May;28(2):546-56 PMID: 6772562
  28. Mucoid conversion of Pseudomonas aeruginosa by hydrogen peroxide: a mechanism for virulence activation in the cystic fibrosis lung.
    Microbiology. 1999 Jun;145 ( Pt 6):1349-57 PMID: 10411261
  29. The penetration of antibiotics into aggregates of mucoid and non-mucoid Pseudomonas aeruginosa.
    J Gen Microbiol. 1989 May;135(5):1291-303 PMID: 2516117
  30. Loss of CFTR chloride channels alters salt absorption by cystic fibrosis airway epithelia in vitro.
    Mol Cell. 1998 Sep;2(3):397-403 PMID: 9774978
  31. Multicellular organization in a degradative biofilm community.
    Appl Environ Microbiol. 1994 Feb;60(2):434-46 PMID: 16349173
  32. Epidemiological investigations of the respiratory tract bacteriology in patients with cystic fibrosis.
    Acta Pathol Microbiol Scand B Microbiol Immunol. 1974 Aug;82(4):541-50 PMID: 4153350
  33. Flagellar and twitching motility are necessary for Pseudomonas aeruginosa biofilm development.
    Mol Microbiol. 1998 Oct;30(2):295-304 PMID: 9791175
  34. Allelic exchange in Pseudomonas aeruginosa using novel ColE1-type vectors and a family of cassettes containing a portable oriT and the counter-selectable Bacillus subtilis sacB marker.
    Mol Microbiol. 1992 May;6(9):1195-204 PMID: 1588818
  35. Initiation of biofilm formation in Pseudomonas fluorescens WCS365 proceeds via multiple, convergent signalling pathways: a genetic analysis.
    Mol Microbiol. 1998 May;28(3):449-61 PMID: 9632250
  36. Cystic fibrosis transmembrane conductance regulator is an epithelial cell receptor for clearance of Pseudomonas aeruginosa from the lung.
    Proc Natl Acad Sci U S A. 1997 Oct 28;94(22):12088-93 PMID: 9342367
  37. Transposon vectors containing non-antibiotic resistance selection markers for cloning and stable chromosomal insertion of foreign genes in gram-negative bacteria.
    J Bacteriol. 1990 Nov;172(11):6557-67 PMID: 2172216
  38. Quantification of biofilm structures by the novel computer program COMSTAT.
    Microbiology. 2000 Oct;146 ( Pt 10):2395-407 PMID: 11021916
  39. Microbial pathogenesis in cystic fibrosis: mucoid Pseudomonas aeruginosa and Burkholderia cepacia.
    Microbiol Rev. 1996 Sep;60(3):539-74 PMID: 8840786
  40. Susceptibility of bacterial biofilms to tobramycin: role of specific growth rate and phase in the division cycle.
    J Antimicrob Chemother. 1990 Apr;25(4):585-91 PMID: 2190969
  41. Theoretical aspects of antibiotic diffusion into microbial biofilms.
    Antimicrob Agents Chemother. 1996 Nov;40(11):2517-22 PMID: 8913456
  42. Negative control of flagellum synthesis in Pseudomonas aeruginosa is modulated by the alternative sigma factor AlgT (AlgU).
    J Bacteriol. 1999 Dec;181(23):7401-4 PMID: 10572149
  43. Mechanism of conversion to mucoidy in Pseudomonas aeruginosa infecting cystic fibrosis patients.
    Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8377-81 PMID: 8378309
  44. Quorum-sensing signals indicate that cystic fibrosis lungs are infected with bacterial biofilms.
    Nature. 2000 Oct 12;407(6805):762-4 PMID: 11048725
  45. Alginate inhibition of the uptake of Pseudomonas aeruginosa by macrophages.
    J Gen Microbiol. 1988 Jan;134(1):29-36 PMID: 3141564
  46. Molecular tools for study of biofilm physiology.
    Methods Enzymol. 1999;310:20-42 PMID: 10547780
  47. The algT (algU) gene of Pseudomonas aeruginosa, a key regulator involved in alginate biosynthesis, encodes an alternative sigma factor (sigma E).
    Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7941-5 PMID: 7644517
  48. Microbiology of airway disease in patients with cystic fibrosis.
    Clin Microbiol Rev. 1991 Jan;4(1):35-51 PMID: 1900735
  49. Microbial biofilms.
    Annu Rev Microbiol. 1995;49:711-45 PMID: 8561477
  50. Biofilm susceptibility to antimicrobials.
    Adv Dent Res. 1997 Apr;11(1):160-7 PMID: 9524452
  51. Role of alginate and its O acetylation in formation of Pseudomonas aeruginosa microcolonies and biofilms.
    J Bacteriol. 2001 Feb;183(3):1047-57 PMID: 11208804
  52. Human beta-defensin-1 is a salt-sensitive antibiotic in lung that is inactivated in cystic fibrosis.
    Cell. 1997 Feb 21;88(4):553-60 PMID: 9038346
Article Info
Journal
Journal of bacteriology
Abbr.
J Bacteriol
ISSN
0021-9193
DOI
10.1128/JB.183.18.5395-5401.2001
Published
2001-09-00
Pages
5395-401
Language
English
Region
United States
NLM ID
2985120R
PMCID
PMC95424
Subset
IM
External Links
PubMed source DOI: 10.1128/JB.183.18.5395-5401.2001 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2