Chapter 18 : Role for Biofilms in Infectious Disease

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in

Role for Biofilms in Infectious Disease, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555817718/9781555818944_Chap18-1.gif /docserver/preview/fulltext/10.1128/9781555817718/9781555818944_Chap18-2.gif


This chapter examines the mutualistic, commensal, and parasitic roles that biofilms play in human biology and health by using an organ system/medical specialty approach. Recently there has been a growing awareness that a number of nondevice-related chronic inflammatory conditions are, in fact, also biofilm-related. Many of these conditions, including cystic fibrosis, chronic obstructive pulmonary disease (COPD), otitis media, and prostatitis, are highly visible and prevalent diseases. Antibiotic sensitivities are generally determined by observing the zone of planktonic growth inhibition around a disc containing the antibiotic of interest. This chapter deals primarily with two topics: (i) how the phenotypic and genotypic characterization of biofilm bacteria has provided the data for the development of a new conceptual framework for the understanding of chronic infections and (ii) the medical effects of biofilm formation on host tissues and implanted medical devices. The cardinal clinical feature of bacterial biofilms is their refractoriness to nearly all host defense mechanisms and conventional therapeutics, including antibiotics. The removal of a single prosthetic joint due to biofilm infection is followed by the intravenous administration of hundreds of thousands of dollars of antibiotics. Bacterial and candidal vaginosis result when there is a disruption of the normal vaginal flora resulting in overgrowth of pathogenic bacteria and fungi.

Citation: Ehrlich G, Hu F, Post J. 2004. Role for Biofilms in Infectious Disease, p 332-358. In Ghannoum M, O'Toole G (ed), Microbial Biofilms. ASM Press, Washington, DC. doi: 10.1128/9781555817718.ch18
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of FIGURE 1

O concentration measurements in a biofilm. O concentration is important in determining the growth rate and antibiotic susceptibility of the bacteria. (A) Oxygen concentration, measured with a microelectrode, decreases with depth into the biofilm. (B) Result of an experiment in which the electrode was left at the final depth (70 µm) where the O2 tension was low. The O2 concentration changes dramatically in response to changes in the availability of the carbon (glucose) and nitrogen (ammonium) source (denoted as C and N). The experiment shows that when the C and N sources are removed from the medium, O2 levels increase due to decreased consumption. (Provided by Phil Stewart.)

Citation: Ehrlich G, Hu F, Post J. 2004. Role for Biofilms in Infectious Disease, p 332-358. In Ghannoum M, O'Toole G (ed), Microbial Biofilms. ASM Press, Washington, DC. doi: 10.1128/9781555817718.ch18
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 2

Scanning electron micrograph of the outer surface of a ventricular-peritoneal shunt removed from a patient. Note the extensive sp. biofilm present on the surface, in which bacteria can be seen embedded in a glycocalyx. The specimen was fixed and dehydrated prior to imaging, which results in a collapse of the biofilm matrix around the bacteria. The bar in the lower right indicates 1 _m. Image supplied by R. Veeh.

Citation: Ehrlich G, Hu F, Post J. 2004. Role for Biofilms in Infectious Disease, p 332-358. In Ghannoum M, O'Toole G (ed), Microbial Biofilms. ASM Press, Washington, DC. doi: 10.1128/9781555817718.ch18
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Akiyama, H.,, H. Kanzaki,, J. Tada,, and J. Arata. 1996. Staphylococcus aureus infection on cut wounds in the mouse skin: experimental staphylococcal botryomycosis. J. Dermatol. 11: 234 238.
2. Akiyama, H.,, R. Torigoe,, and J. Arata. 1993. Interaction of Staphylococcus aureus cells and silk threads in vitro and in mouse skin. J. Dermatol. 6: 247 257.
3. Alfa, M. J.,, A. Llnyckyj,, N. MacFarlane,, V. Preece,, S. Allford,, and B. Fachnie. 2002. Microbial overgrowth in water perfusion equipment for esophageal/rectal motility. Gastrointest. Endosc. 55: 209 213.
4. Anderson, B. E.,, J. E. Dawson,, D. C. Jones,, and K. H. Wilson. 1991. Ehrlichia chaffeensis, a new species associated with human ehrlichiosis. J. Clin. Microbial. 29: 2838 2842.
5. Anwar, H.,, J. L. Strap,, and J. W. Costerton. 1992. Establishment of aging biofilms: possible mechanism of bacterial resistance to antimicrobial therapy. Antimicrob. Agents Chemother. 36: 1347 1351.
6. Barer, M. R.,, and C. R. Harwood. 1999. Bacterial viability and culturability. Adv. Microb. Physiol. 41: 93 137.
7. Brown, M. R.,, D. G. Allison,, and P. Gilbert. 1998. Resistance of bacterial biofilms to antibiotics: a growth rate effect? J. Antimicrob. Chemother. 22: 777 780.
8. Brown, M. R.,, and J. Barker. 1999. Unexplored reservoirs of pathogenic bacteria: protozoa and biofilms. Trends Microbiol. 7: 46 50.
9. Calderwood, S. B.,, L. A. Swinski,, C. M. Waternaux,, A. W. Karchmer,, and M. J. Buckley. 1985. Risk factors for the development of prosthetic valve endocarditis. Circulation 72: 31 37.
10. Caldwell, D. E., et al. 1997. Germ theory vs. community theory in understanding and controlling the proliferation of biofilms. Adv. Dent. Res. 11: 4 13.
11. Chole, R. A.,, and B. T. Faddis. 2002. Evidence for microbial biofilms in cholesteatomas. Arch. Otolaryngol. Head Neck Surg. 128: 1129 1133.
12. Chole, R. A.,, and B. T. Faddis. 2003. Anatomical evidence of microbial biofilms in tonsillar tissues: a possible mechanism to explain chronicity. Arch. Otolaryngol. Head Neck Surg. 129: 634 636.
13. Choong, S.,, and H. Whitfield. 2000a. Biofilms and their role in infections in urology. BJU Int. 86: 935 941.
14. Choong, S. K. S.,, and H. N. Whitfield. 2000b. Urinary encrustation of alloplastic materials. J. Endourol. 14: 19 23.
15. Cook, G.,, J. W. Costerton,, and R. O. Darouiche. 2000. Direct confocal microscopy studies of the bacterial colonization in vitro of a silver-coated heart valve sewing cuff. Int. J. Antimicrob. 13: 169 173.
16. Costerton, J. W.,, G. G. Geesey,, and K. J. Cheng. 1978. How bacteria stick. Sci. Am. 238: 86 95.
17. Costerton, J. W.,, and P. S. Stewart. 2001. Battling biofilms. Sci. Am. 285: 74 81.
18. Costerton, J. W.,, P. S. Stewart,, and E. P. Greenberg. 1999. Bacterial biofilms: a common cause of persistent infections. Science 284: 1318 1322.
19. Costerton, J. W.,, Z. Lewandowski,, D. E. Caldwell,, D. R. Korber,, and H. M. Lappin- Scott. 1995. Microbial biofilms. Annu. Rev. Microbiol. 49: 711 745.
20. Dasgupta, M. K. 2002. Biofilms and infection in dialysis patients. Semin. Dial. 15: 338 346.
21. Dingman, J. R.,, M. G. Rayner,, S. Mishra,, Y. Zhang,, J. C. Post,, and G. D. Ehrlich. 1998. Correlation between presence of viable bacteria and presence of endotoxin in middle-ear effusions. J. Clin. Microbiol. 36: 3417 3419.
22. Domingue, P. A.,, K. Sadhu,, J. W. Costerton,, K. Bartlett,, and A. W. Chow. 1991. The human vagina: normal flora considered as an in situ tissue-associated, adherent biofilm. Genitourin. Med. 67: 226 231.
23. Duncan, A. J.,, R. J. Carman,, G. J. Olsen,, and K. H. Wilson. 1993. The agent of Tyzzer’s disease is a Clostridium species. Clin. Infect. Dis. 16(Suppl. 4): S422.
24. Ehrlich, G. D.,, R. Veeh,, X. Wang,, J. W. Costerton,, J. D. Hayes,, F. Z. Hu,, B. J. Daigle,, G. D. Ehrlich,, and J. C. Post. 2002. Mucosal biofilm formation on middle-ear mucosa in the chinchilla model of otitis media. JAMA 287: 1710 1715.
25. Ehrlich, G. D.,, V. Weedn,, S. Kathju,, J. Peterson,, N. Balaban,, M. Shirtliff,, C. Post,, Q. Lin,, P. Leduc,, F. Z. Hu,, T. Kaiser,, J. Becker,, N. Sotereanos,, and W. Costerton. 2003. Development of intelligent implants for biofilm prevention in orthopedic prostheses. In ASM Conference on Bio-, Micro-, and Nanosystems, July 10, 2003, New York, N.Y.
26. Elder, M. J.,, F. Stapleton,, E. Evans,, and J. K. Dart. 1995. Biofilm-related infections in ophthalmology. Eye 9: 102 109.
27. Elves, A. W. S.,, and R. C. L. Feneley. 1997. Long-term urethral catheterization and the urinebiomaterial interface. BJU 80: 1 5.
28. Fredericks, D. N.,, and D. A. Relman. 1996. Sequence-based identification of microbial pathogens: a reconsideration of Koch’s postulates. Clin. Microbiol. Rev. 9: 18 33.
29. Fulcher, T. P., et al. 2001. Demonstration of biofilm in infectious crystalline keratopathy using ruthenium red and electron microscopy. Ophthalmology 108: 1088 1092.
30. Fux, C. A., et al. 2003. Bacterial biofilms: a diagnostic and therapeutic challenge. Exp. Rev. Anti- Infect. Ther. 1: 667 683.
31. Geesey, G. G.,, W. T. Richardson,, H. G. Yeomans,, R. T. Irvin,, and J. W. Costerton. 1977. Microscopic examination of natural sessile bacterial populations from an alpine stream. Can. J. Microbiol. 23: 1733 1736.
32. Gorman, S. P.,, W. M. Mawhinney,, C. G. Adair,, and M. Issouckis. 1993. Confocal laser scanning microscopy of peritoneal catheter surfaces. J. Med. Microbiol. 38: 411 417.
33. Hyde, J. A. J.,, R. O. Darouiche,, and J. W. Costerton. 1998. Strategies for prophylaxis against prosthetic valve endocarditis: a review article. J. Heart Valve Dis. 7: 316 326.
34. Ko, W.,, and G. A. Fantini. 1994. Prosthetic graft infection involving the thoracic aorta: graft excision and extra-anatomic revascularization. Cardiovasc. Surg. 2: 81 84.
35. Leung, J. W. C.,, J. Y. Sung,, and J. W. Costerton. 1989. Bacteriological and electron microscopy examination of brown pigment stones. J. Clin. Microbiol. 27: 915 921.
36. Lewis, R. M. 2002. Airway clearance techniques for the patient with an artificial airway. Respir. Care 47: 808 817.
37. Man, N. K.,, A. Degremont,, J. C. Darbord,, M. Collet,, and P. Vaillant. 1998. Evidence of bacterial biofilm in tubing from hydraulic pathway of hemodialysis system. Artif. Organs 22: 596 600.
38. Mannino, D. M.,, D. M. Homa,, L. J. Akinbami,, E. S. Ford,, and S. C. Redd. 2002. Chronic obstructive pulmonary disease surveillance-United States, 1971-2000. Morb. Mortal. Wkly. Rep. 51: 1 16.
39. Marrie, T. J., et al. 1983. Examination of the morphology of bacteria adhering to peritoneal dialysis catheters by scanning and transmission electron microscopy. J. Clin. Microbiol. 18: 1388 1398.
40. Miyanaga, Y. 1997. A new perspective in ocular infection and the role of antibiotics. Ophthalmologica 211(Suppl 1): 9 14.
41. Murphy, T. F.,, and C. Kirkham. 2002. Biofilm formation by nontypeable Haemophilus influenzae: strain variability, outer membrane antigen expression and role of pili. BMC Microbiol. 15: 7.
42. Murphy, T. F.,, S. Sethi,, K. L. Klingman,, A. B. Brueggemann,, and G. V. Doern. 1999. Simultaneous respiratory tract colonization by multiple strains of nontypeable Haemophilus influenzae in chronic obstructive pulmonary disease: implications for antibiotic therapy. J. Infect. Dis. 180: 404 409.
43. Murphy, T. F.,, S. Sethi,, and M. S. Niederman. 2000. The role of bacteria in exacerbations of COPD. A constructive view. Chest 118: 204 209.
44. Nase, L.,, K. Hatakka,, E. Savilahti,, M. Saxelin,, A. Ponka,, T. Poussa,, R. Korpela,, and J. H. Meurman. 2001. Effect of long-term consumption of a probiotic bacterium, Lactobacillus rhamnosus GG, in milk on dental caries and caries risk in children. Caries Res. 35: 412 420.
45. Nickel, J. C.,, J. Downey,, and J. W. Costerton. 1992. Movement of Pseudomonas aeruginosa along catheter surfaces. Urology 19: 93 98.
46. Passerini, L.,, K. Lam,, J. W. Costerton,, and E. G. King. 1992. Biofilms on indwelling vascular catheters. Care Med. 20: 665 673.
47. Passerini, L.,, P. T. Phang,, F. L. Jackson,, K. Lam,, J. W. Costerton,, and E. G. King. 1987. Biofilms on right heart flow-directed catheters. Chest 92: 440 446.
48. Post, J. C. 2001. Direct evidence of bacterial biofilms in otitis media. Laryngoscope 111: 2083 2094.
49. Post, J. C.,, and G. E. Ehrlich. 2000. The impact of the polymerase chain reaction in clinical medicine. JAMA 283: 1544 1546.
50. Post, J. C.,, J. J. Aul,, G. J. White,, R. M. Wadowsky,, T. Zavoral,, R. Tabari,, B. Kerber,, W. J. Doyle,, and G. D. Ehrlich. 1996. PCR-based detection of bacterial DNA after antimicrobial treatment is indicative of persistent, viable bacteria in the chinchilla model of otitis media. Am. J. Otolaryngol. 17: 106 111.
51. Post, J. C., et al. 1995. Molecular analysis of bacterial pathogens in otitis media with effusion. JAMA 273: 1598 1604.
52. Potera, C. 1996. Biofilms invade microbiology. Science 273: 1795 1797.
53. Probert, H. M.,, and G. R. Gibson. 2002. Bacterial biofilms in the human gastrointestinal tract. Curr. Issues Intest. Microbiol. 3: 23 27.
54. Raad, I. I. 1994. The pathogenesis and prevention of central venous catheter-related infections. Middle East J. Anesth. 12: 381 403.
55. Rayner, M. G.,, Y. Zhang,, M. C. Gorry,, Y. Chen,, J. C. Post,, and G. D. Ehrlich. 1998. Evidence of Bacterial metabolic activity in culturenegative otitis media with effusion. JAMA 279: 296 299.
56. Reid, G.,, C. Tieszer,, and D. Lam. 1995. Influence of lactobacilli on the adhesion of Staphylococcus aureus and Candida albicans to fibers and epithelial cells. J. Ind. Microbiol. 15: 248 253.
57. Reid, G.,, J. Hsiehl,, P. Potter,, J. Mighton,, D. Lam,, D. Warren,, and J. Stephenson. 2001. Cranberry juice consumption may reduce biofilms on uroepithelial cells: pilot study in spinal cord injured patients. Spinal Cord 39: 26 30.
58. Relman, D. A.,, J. S. Loutit,, T. M. Schmidt,, S. Falkow,, and L. S. Tompkins. 1990. The agent of bacillary angiomatosis. An approach to the identification of uncultured pathogens. N. Engl. J. Med. 6: 1573 1580.
59. Sauer, K.,, A. K. Camper,, G. D. Ehrlich,, J. W. Costerton,, and D. G. Davies. 2002. Pseudomonas aeruginosa displays multiple phenotypes during development of a biofilm. J. Bacteriol. 184: 1140 1154.
60. Schnarr, S.,, N. Putschky,, M. C. Jendro,, H. Zeidler,, M. Hammer,, J. G. Kuipers,, and J. Wollenhaupt. 2001. Chlamydia and Borrelia DNA in synovial fluid of patients with early undifferentiated oligoarthritis: results of a prospective study. Arthritis Rheum. 44: 2679 2685.
61. Schulin, T.,, and A. Voss. 2001. Coagulase-negative staphylococci as a cause of infections related to intravascular prosthetic devices: limitations of present therapy. Clin. Microbiol. Infect. 7(Suppl. 4): 1 7.
62. Schwab, U., et al. 2002. Patterns of epithelial cell invasion by different species of the Burkholderia cepacia complex in well-differentiated human airway epithelia. Infect. Immun. 70: 4547 4555.
63. Sedor, J.,, and S. G. Mulholland. 1999. Hospitalacquired urinary tract infections associated with the indwelling catheter. Urol. Clin. N. Am. 26: 821 828.
64. Shen, K.,, X. Wang,, J. C. Post,, and G. D. Ehrlich,. 2003. Molecular and translational research approaches for the study of bacterial pathogenesis in otitis media, p. 91 119. In R. Rosenfeld, and C. D. Bluestone (ed.), Evidence-Based Otitis Media, 2nd ed. B. C. Decker, Inc., Hamilton, Ontario, Canada.
65. Shigeta, M.,, G. Tanaka,, H. Komatsuzawa,, M. Sugai,, H. Suginaka,, and T. Usui. 1997. Permeation of antimicrobial agents through Pseudomonas aeruginosa biofilms: a simple method. Chemotherapy. 43: 340 345.
66. Sofer, M.,, and J. D. Denstedt. 2000. Encrustation of biomaterials in the urinary tract. Curr. Opin. Urol. 10: 563 569.
67. Spencer, R. C. 1988. Infections in continuous ambulatory peritoneal dialysis. J. Med. Microbiol. 27: 1 9.
68. Stewart, P. S. 2001. Multicellular resistance: biofilms. Trends Microbiol. 9: 204.
69. Stewart, P. S.,, and J. W. Costerton. 2001. Antibiotic resistance of bacteria in biofilms. Lancet 14: 135 138.
70. Suci, P. A.,, M. W. Mittelman,, F. P. Yu,, and G. G. Geesey. 1994. Investigation of ciprofloxacin penetration into Pseudomonas aeruginosa biofilms. Antimicrob. Agents Chemother. 38: 2125 2133.
71. Sung, J. J. Y. 1995. Bacterial biofilm and clogging of biliary stents. J. Ind. Micro. 15: 152 155.
72. Swidsinski, A.,, and S. P. Lee. 2001. The role of bacteria in gallstone pathogenesis. Front Biosci. 1: 93 103.
73. Tunney, M. M.,, S. Patrick,, M. D. Curran,, G. Ramage,, D. Hanna,, J. R. Nixon,, S. P. Gorman,, R. I. Davis,, and N. Anderson. 1999. Detection of prosthetic hip infection at revision arthroplasty by immunofluorescence microscopy and PCR amplification of the bacterial 16S rRNA gene. J. Clin. Microbiol. 37: 3281 3290.
74. van Alphen, L.,, D. A. Caugant,, B. Duim,, M. O’Rourke,, and L. D. Bowler. 1997. Differences in genetic diversity of nonecapsulated Haemophilus influenzae from various diseases. Microbiology 143: 1423 1431.
75. van Alphen, L.,, H. M. Jansen,, and J. Dankert. 1995. Virulence factors in the colonization and persistence of bacteria in the airways. Am. J. Respir. Crit. Care Med. 151: 2094 2100.
76. van der Mei, H. C.,, R. H. Free,, G. J. Elving,, R. Van Weissenbruch,, F. W. Albers,, and H. J. Busscher. 2000. Effect of probiotic bacteria on prevalence of yeasts in oropharyngeal biofilms on silicone rubber voice prostheses in vitro. J. Med. Microbiol. 49: 713 718.
77. Veeh, R. H.,, M. E. Shirtliff,, J. R. Petik,, J. A. Flood,, C. C. Davis,, J. L. Seymour,, M. A. Hansmann,, K. M. Kerr,, M. E. Pasmore,, and J. W. Costerton. 2003. Detection of Staphylococcus aureus biofilm on tampons and menses components. J. Infect. Dis. 188: 519 530.
78. Vercellotti, G. M. 2001. Overview of infections and cardiovascular diseases. J. Allergy Clin. Immunol. 108(4 Suppl): S117 S120.
79. Vincent, F. C.,, A. R. Tibi,, and J. C. Darbord. 1989. A bacterial biofilm in a hemodialysis system. ASAIO Trans. 35: 310 313.
80. Virden, C. P.,, M. K. Dobke,, P. Stein,, C. L. Parsons,, and D. H. Frank. 1992. Subclinical infection of the silicone breast implant surface as a possible cause of capsular contracture. Aesth. Plast. Surg. 16: 173 179.
81. Vlessis, A. A.,, A. Khaki,, G. L. Grunkemeier,, H. H. Li,, and A. Stan. 1997. Risk, diagnosis and management of prosthetic valve endocarditis: a review. J. Heart Valve Dis. 6: 443 465.
82. Vrany, J. D.,, P. S. Stewart,, and P. A. Suci. 1997. Comparison of recalcitrance to ciprofloxacin and levofloxacin exhibited by Pseudomonas aeruginosa biofilms displaying rapid-transport characteristics. Antimicrob. Agents Chemother. 41: 1352 1358.
83. Walters, M. C., III,, F. Roe,, A. Bugnicourt,, M. J. Franklin,, and P. S. Stewart. 2003. Contributions of antibiotic penetration, oxygen limitation, and low metabolic activity to tolerance of Pseudomonas aeruginosa biofilms to ciprofloxacin and tobramycin. Antimicrob. Agents Chemother. 47: 317 323.
84. Whitchurch, C. B.,, T. Tolker-Nielsen,, P. C. Ragas,, and J. S. Mattick. 2002. Extracellular DNA required for bacterial biofilm formation. Science 295: 1487.
85. Wilson, K. H., 1994a. Characterization of novel bacterial pathogens by amplification and sequencing of 16S ribosomal genes, p. 649 664. In G. D. Ehrlich, and S. J. Greenberg (ed.), PCR-Based Diagnostics in Infectious Disease. Blackwell Scientific Publications, Boston, Mass.
86. Wilson, K. H. 1994b. Detection of culture-resistant bacterial pathogens by amplification and sequencing of ribosomal DNA. Clin. Infect. Dis. 18: 958 962.
87. Wilson, K. H.,, R. B. Blitchington,, R. Frothingham,, and J. A. Wilson. 1993. Identification of the Whipple’s disease bacillus. N. Engl. J. Med. 328: 62.
88. Xu, K. D.,, M. J. Franklin,, C. H. Park,, G. A. McFeters,, and P. S. Stewart. 2001. Gene expression and protein levels of the stationary phase sigma factor, RpoS, in continuously-fed Pseudomonas aeruginosa biofilms. FEMS Microbiol. Lett. 199: 67 71.
89. Xu, K. D.,, P. S. Stewart,, F. Xia,, C. T. Huang,, and G. A. McFeters. 1998. Spatial physiological heterogeneity in Pseudomonas aeruginosa biofilm is determined by oxygen availability. Appl. Environ. Microbiol. 64: 4035 4039.
90. Yasuda, H.,, Y. Ajiki,, T. Koga,, H. Kawada,, and T. Yokota. 1993. Interaction between biofilms formed by Pseudomonas aeruginosa and clarithromycin. Antimicrob. Agents Chemother. 37: 1749 1755.
91. Yokoi, N.,, K. Okada,, J. Sugita,, and S. Kinoshita. 2000. Acute conjunctivitis associated with biofilm formation on a punctal plug. Jpn. J. Ophthalmol. 44: 559 560.
92. Zegans, M. E.,, H. I. Becker,, J. Budzik,, and G. O’Toole. 2002. The role of bacterial biofilms in ocular infections. DNA Cell Biol. 21: 415 420.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error