Semin Respir Crit Care Med 2003; 24(6): 663-670
DOI: 10.1055/s-2004-815662
Copyright © 2003 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

The Role of Biofilms in Airway Disease

Kara Jackson, Rebecca Keyser, Daniel J. Wozniak
  • Wake Forest University School of Medicine, Department of Microbiology and Immunology, Winston-Salem, North Carolina
Further Information

Publication History

Publication Date:
15 January 2004 (online)

ABSTRACT

Biofilms are defined as collections of microorganisms attached to a surface and embedded in a matrix. This attached state is the primary mode of microbial growth in the environment and within the body. However, biofilms represent a significant clinical concern because they are recalcitrant to antimicrobial agents. This is particularly troublesome in the respiratory tract where biofilms clearly complicate traditional therapies. This review focuses on the biology, development, and antimicrobial resistance properties of biofilms formed by three significant respiratory tract pathogens; Pseudomonas aeruginosa, Staphylococcus aureus, and Haemophilus influenzae. Recent research has begun to shed light on the molecular events governing biofilm formation and antimicrobial resistance mechanisms with these organisms. A deeper understanding of these concepts will be necessary for the development of rational strategies to control biofilms in the future.

REFERENCES

  • 1 Costerton J W, Lewandowski Z, Caldwell D E, Korber D R, Lappin-Scott H M. Microbial biofilms.  Annu Rev Microbiol . 1995;  49 711-745
  • 2 O'Toole G, Kaplan H B, Kolter R. Biofilm formation as microbial development.  Annu Rev Microbiol . 2000;  54 49-79
  • 3 Donlan R M, Costerton J W. Biofilms: survival mechanisms of clinically relevant microorganisms.  Clin Microbiol Rev . 2002;  15 167-193
  • 4 Douglas L J. Candida biofilms and their role in infection.  Trends Microbiol . 2003;  11 30-36
  • 5 Fuqua C, Greenberg E P. Listening in on bacteria: acyl-homoserine lactone signaling.  Nat Rev Mol Cell Biol . 2002;  3 685-695
  • 6 Kolenbrander P E, Andersen R N, Blehert D S, Egland P G, Foster J S, Palmer Jr J R. Communication among oral bacteria.  Microbiol Mol Biol Rev . 2002;  66 486-505
  • 7 Stewart P S. Diffusion in biofilms.  J Bacteriol . 2003;  185 1485-1491
  • 8 Stoodley P, Sauer K, Davies D G, Costerton J W. Biofilms as complex differentiated communities.  Annu Rev Microbiol . 2002;  56 187-209
  • 9 Costerton J W, Stewart P S, Greenberg E P. Bacterial biofilms: a common cause of persistent infections.  Science . 1999;  284 1318-1322
  • 10 Mah T C, O'Toole G A. Mechanisms of biofilm resistance to antimicrobial agents.  Trends Microbiol . 2001;  9 34-39
  • 11 Licking E. Getting a grip on bacterial slime.  Bus Week . 1999;  13 98-100
  • 12 Darouiche R O. Device-associated infections: a macroproblem that starts with microadherence.  Clin Infect Dis . 2001;  33 1567-1572
  • 13 National Institutes of Health. Research on microbial biofilms. Available at: http://grants1.nih.gov/grants/guide/pa-files/PA-03-047.html. Accessed 12/20/02
  • 14 Palmer Jr J R, Wu R, Gordon S. et al . Retrieval of biofilms from the oral cavity.  Methods Enzymol . 2001;  337 393-403
  • 15 Feuille F, Ebersole J, Kesavalu L, Stepfen M, Holt S. Mixed infection with Porphyromonas gingivalis and Fusobacterium nucleatum in a murine lesion model: potential synergistic effects on virulence.  Infect Immun . 1996;  64 2094-2100
  • 16 Budhani R K, Struthers J K. The use of Sorbarod biofilms to determine the antimicrobial susceptibilities of a strain of Streptococcus pneumoniae J Antimicrob Chemother .  1997;  40 601-602
  • 17 Budhani R K, Struthers J K. Interaction of Streptococcus pneumoniae and Moraxella catarrhalis: investigation of the indirect pathogenic role of beta-lactamase-producing Moraxellae by use of a continuous-culture biofilm system.  Antimicrob Agents Chemother . 1998;  42 2521-2526
  • 18 Ehrlich G D, Veeh R, Wang X. et al . Mucosal biofilm formation on middle-ear mucosa in the chinchilla model of otitis media.  JAMA . 2002;  287 1710-1715
  • 19 Murphy T F, Kirkham C. Biofilm formation by nontypeable Haemophilus influenzae: strain variability, outer membrane antigen expression and role of pili.  BMC Microbiol . 2002;  2 1-8
  • 20 O'Toole G, Pratt L A, Watnick P I, Newman D K, Weaver V B, Kolter R. Genetic approaches to study biofilms.  Methods Enzymol . 1999;  310 91-109
  • 21 O'Toole G A, Kolter R. Flagellar and twitching motility are necessary for Pseudomonas aeruginosa biofilm development.  Mol Microbiol . 1998;  30 295-304
  • 22 Sheikh J, Hicks S, Dall'Agnol M, Phillips A D, Nataro J P. Roles for Fis and YafK in biofilm formation by enteroaggregative Escherichia coli Mol Microbiol .  2001;  41 983-997
  • 23 O'Toole G A. Initiation of biofilm formation in Pseudomonas fluorescens WCS365 proceeds via multiple convergent signalling pathways: a genetic analysis.  Mol Microbiol . 1998;  28 449-461
  • 24 Stover C K, Pham X Q, Erwin A L. et al . Complete genome sequence of Pseudomonas aeruginosa PA01, an opportunistic pathogen.  Nature . 2000;  406 959-964
  • 25 Lam J, Chan R, Lam K, Costerton J RW. Production of mucoid microcolonies by Pseudomonas aeruginosa within infected lungs in cystic fibrosis.  Infect Immun . 1980;  28 546-556
  • 26 Hoiby N, Johansen H K, Moser C, Song Z, Ciofu O, Kharazmi A. Pseudomonas aeruginosa and the in vitro and in vivo biofilm mode of growth.  Microbes Infect . 2001;  3 23-35
  • 27 Singh P K, Schaefer A L, Parsek M R, Moninger T O, Welsh M J, Greenberg E P. Quorum-sensing signals indicate that cystic fibrosis lungs are infected with bacterial biofilms.  Nature . 2000;  407 762-764
  • 28 Whitchurch C B, Erova T E, Emery J A. et al . Phosphorylation of the Pseudomonas aeruginosa response regulator AlgR is essential for type IV fimbria-mediated twitching motility.  J Bacteriol . 2002;  184(16) 4544-4554
  • 29 Davies D G, Parsek M R, Pearson J P, Iglewski B H, Costerton J W, Greenberg E P. The involvement of cell-to-cell signals in the development of a bacterial biofilm.  Science . 1998;  280 295-298
  • 30 Evans L R, Linker A. Production and characterization of the slime polysaccharide of Pseudomonas aeruginosa J Bacteriol .  1973;  116 915-924
  • 31 Costerton J, Brown M RW, Lam J, Lam K, Cochrane D MG. The microcolony mode of growth in vivo: an ecological perspective. In: Gacesa P, Russel NJ, eds. Pseudomonas Infection and Alginates: Biochemistry, Genetics and Pathology London: Chapman and Hall 1990: 76-94
  • 32 Davies D G, Chakrabarty A M, Geesey G G. Exopolysaccharide production in biofilms: substratum activation of alginate gene expression by Pseudomonas aeruginosa Appl Env Microbiol .  1993;  59 1181-1186
  • 33 Whitchurch C B, Tolker-Nielsen T, Ragas P C, Mattick J S. Extracellular DNA required for bacterial biofilm formation.  Science . 2002;  295 1487
  • 34 O'Toole G A, Gibbs K A, Hager P W, Phibbs Jr V P, Kolter R. The global carbon metabolism regulator Crc is a component of a signal transduction pathway required for biofilm development by Pseudomonas aeruginosa J Bacteriol .  2000;  182 425-431
  • 35 Finelli A, Gallant C V, Jarvi K, Burrows L L. Use of in-biofilm expression technology to identify genes involved in Pseudomonas aeruginosa biofilm development.  J Bacteriol . 2003;  185 2700-2710
  • 36 Sauer K, Camper A K, Ehrlich G D, Costerton J W, Davies D G. Pseudomonas aeruginosa displays multiple phenotypes during development as a biofilm.  J Bacteriol . 2002;  184 1140-1154
  • 37 Whiteley Y, Bangera M G, Bumgarnder R E. et al . Gene expression in Pseudomonas aeruginosa biofilms.  Nature . 2001;  413 860-864
  • 38 Worlitzsch D, Tarran R, Ulrich M. et al . Effects of reduced mucus oxygen concentration in airway Pseudomonas infections of cystic fibrosis patients.  J Clin Invest . 2002;  109 317-325
  • 39 Xu K D, Stewart P S, Xia F, Huang C-T, McFeters G A. Spatial physiological heterogeneity in Pseudomonas aeruginosa biofilm is determined by oxygen availability.  Appl Environ Microbiol . 1998;  64 4035-4039
  • 40 Yoon S S, Hennigan R F, Hilliard G M. et al . Pseudomonas aeruginosa anaerobic respiration in biofilm: relationships to cystic fibrosis pathogenesis.  Dev Cell . 2002;  3 593-603
  • 41 Hassett D. Anaerobic production of alginate by Pseudomonas aeruginosa: alginate restricts diffusion of oxygen.  J Bacteriol . 1996;  178 7322-7325
  • 42 Wyckoff T JO, Thomas B, Hassett D J, Wozniak D J. Static growth of mucoid Pseudomonas aeruginosa selects for non-mucoid variants that have acquired flagellum-dependent motility.  Microbiology . 2002;  148 3423-3430
  • 43 Hassett D J, Cuppoletti J, Trapnell B. et al . 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 . 2002;  54 1425-1443
  • 44 von Eiff C, Peters G, Heilmann C. Pathogenesis of infections due to coagulase-negative staphylococci.  Lancet Infect Dis . 2002;  2 677-685
  • 45 Gotz F. Staphylococcus and biofilms.  Mol Microbiol . 2002;  43 1367-1378
  • 46 Schierholz J M, Beuth J. Implant Infections: a haven for opportunistic bacteria.  J Hosp Infect . 2001;  49 87-93
  • 47 Veenstra G, Cremers F, van Dijk H, Fleer A. Ultrastructural organiztion and regulation of a biomaterial adhesin of Staphylococcus epidermidis J Bacteriol .  1996;  178 537-541
  • 48 Cucarella C, Tormo M A, Knecht E. et al . Expression of the biofilm-associated protein interferes with host protein receptors of Staphylococcus aureus and alters the infective process.  Infect Immun . 2002;  70 3180-3186
  • 49 McKenney D, Hubner J, Muller E, Wang Y, Goldmann D A, Pier G. The ica locus of Staphylococcus epidermidis encodes production of the capsular polysaccharide/adhesin.  Infect Immun . 1998;  66 4711-4720
  • 50 Hussain M, Herrmann M, von Eiff C, Perdreau-Remington F, Peters G. A 140-kilodalton extracellular protein is essential for the accumulation of Staphylococcus epidermidis strains on surfaces.  Infect Immun . 1997;  65 519-524
  • 51 Mack D, Fischer W, Krokotsch A. et al . The intercellular adhesin involved in biofilm accumulation of Staphylococcus epidermidis is a linear β-1,6-linked glucosaminoglycan: purification and structural analysis.  J Bacteriol . 1996;  178 175-183
  • 52 Kadurugamuwa J L, Sin L, Albert E. et al . Direct continuous method for monitoring biofilm infection in a mouse model.  Infect Immun . 2003;  71 882-890
  • 53 Balaban N, Goldkorn T, Gov Y. et al . Regulation of Staphylococcus aureus pathogenesis via target of RNAIII-activating protein (TRAP).  J Biol Chem . 2001;  276 2658-2667
  • 54 Balaban N, Goldkorn T, Nhan R T. et al . Autoinducer of virulence as a target for vaccine and therapy against Staphylococcus aureus Science .  1998;  280 438-440
  • 55 Balaban N, Giacometti A, Cirioni O. et al . Use of quorum-sensing inhibitor RNAIII-inhibiting peptide to prevent biofilm formation in vivo by drug-resistant Staphylococcus epidermidis J Infect Dis .  2003;  187 625-630
  • 56 Balaban N, Gov Y, Bitler A, Boelaert J R. Prevention of Staphylococcus aureus biofilm on dialysis catheters and adherence to human cells.  Kidney Int . 2003;  63 340-345
  • 57 Ceri H, Olson M E, Stremick C, Read R R, Morck D, Buret A. The Calgary biofilm device: new technology for rapid determination of antibiotic susceptibilities of bacterial biofilms.  J Clin Microbiol . 1999;  37 1771-1776
  • 58 Spoering A L, Lewis K. Biofilms and planktonic cells of Pseudomonas aeruginosa have similar resistance to killing by antimicrobials.  J Bacteriol . 2001;  183 6746-6751
  • 59 Drenkard E, Ausubel F M. Pseudomonas biofilm formation and antibiotic resistance are linked to phenotypic variation.  Nature . 2002;  416 740-743
  • 60 Walters III C M, Roe F, Bugnicourt A, Franklin M J, Stewart P S. Contributions of antibiotic penetration, oxygen limitation, and low metabolic activity to tolerance of Pseudomonas aeruginosa biofilms to ciprofloxacin and tobramycin.  Antimicrob Agents Chemother . 2003;  47 317-323
  • 61 Lewis K. Riddle of biofilm resistance.  Antimicrob Agents Chemother . 2001;  45 999-1007
  • 62 Prince A. Biofilms, antimicrobial resistance, and airway infection.  N Engl J Med . 2002;  347 1110-1111
  • 63 Stewart P S, Costerton J W. Antibiotic resistance of bacteria in biofilms.  Lancet . 2001;  358 135-138
    >