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Perspective
Biofilms: Microbial Life on
Surfaces
Appendix I: Detachment Cells
or Biofilm Aggregates
Rodney M. Donlan*
*Centers for Disease Control and Prevention, Atlanta, Georgia, USA
As already discussed, cells are routinely detached from biofilms. Sloughing
and erosion may also result in aggregates of cells being shed by the biofilm.
This may be particularly acute for persons with colonized indwelling medical
devices such as central venous catheters. Raad et al. (1)
quantified biofilms on central venous catheters and determined the
relationship between biofilm formation and catheter-related septicemia.
A characteristic of infective endocarditis, a biofilm process on native
heart valves, is the production of emboli (cells or clumps of cells and
associated platelets, fibrin, and erythrocytes). These emboli may cause
serious complications when they are released into the bloodstream. Pathogenic
organisms in potable water biofilms might also detach as aggregates, and,
especially for those organisms with a low infective dose, consumption
or exposure to water containing these organisms might result in infection.
Epidemiologic evidence for this process is lacking, however.
Resistance
to Antimicrobial Agents
Biofilms are highly resistant to most antimicrobial agents and disinfectants
(2). In addition, organisms within biofilms can
readily acquire resistance through the transfer of resistance plasmids.
Such resistance could be especially acute in the health-care environment
for patients with colonized urinary catheters and collection bags. Many
of the enteric organisms shown to colonize urinary catheters carry plasmids
encoding resistance to multiple antimicrobial agents (3).
Transfer of plasmids within biofilms has been well established (as
already discussed). Resistant organisms such as methicillin-resistant
Staphylococcus aureus have also been shown to form biofilms
(4).
Production
of Endotoxins
Gram-negative bacteria within biofilms of indwelling medical devices
will produce endotoxins. Production of such toxins could be especially
relevant for hemodialysis patients, since endotoxins from dialysate may
be transported across the dialysis membrane of the dialyzer. Vincent et
al. (5) measured endotoxin levels on hemodialysis
tubing and showed a correlation with bacterial biofilm counts. Other studies
have also measured endotoxin levels of biofilms (6,7).
However, the kinetics of endotoxin release from biofilms has not been
documented.
Resistance
to Host Immune System Clearance
Evidence has been provided to support the hypothesis that microorganisms
detaching from biofilms on indwelling medical devices could overcome the
host immune system and cause an infection. Ward et al. (8)
showed that the immune system of a vaccinated rabbit had no effect
(in terms of phagocytosis) on the growth of bacteria in a biofilm on an
implanted peritoneal device in the animal. The vaccinated animals had
a 1,000-fold higher titer of the antibody than did nonvaccinated animals,
but the antibodies apparently did not reach the surface of the bacterial
cells within the biofilm. Shiau and Wu (9) showed
that the extracellular polymeric substance matrix produced by S. epidermidis
interfered with macrophage phagocytic activity. Meluleni et al. (10)
found that opsonic antibodies made by patients with chronic cystic
fibrosis were unable to mediate phagocytosis and eliminate bacterial cells
growing in biofilm microcolonies. Yasuda et al. (11)
showed that resuspended biofilm cells of Escherichia coli were
less sensitive to the killing activity of human polymorphonuclear leukocytes
(PMNL) in vitro and suggested that this was due to resistance of the biofilm
organisms to the active oxygen species produced by the PMNL. This
indicates that cells detaching from biofilms in indwelling medical devices
may have the ability to survive the PMNL phagocytic activity in the bloodstream
to initiate a bloodstream infection.
References
- Raad II, Sabbagh MF, Rand KH, Sherertz RJ. Quantitative
tip culture methods and the diagnosis of central venous catheter-related
infections. Diagn Microbiol Infect Dis 1992;15:13–20.
- Donlan RM. Role
of biofilms in antimicrobial resistance. ASAIO J 2000;46:S47–S52.
- Sedor J, Mulholland SG. Hospital
acquired urinary tract infections associated with the indwelling catheter.
Urol Clin North Am 1999;26:821–8.
- Murga R, McAllister S, Miller JM, Tenover F, Bell M, Donlan RM. Effect
of vancomycin treatment of methicillin-resistant S. aureus (MRSA)
biofilms on central venous catheters in a model system. Poster No. C276
presented at the 2001 American Society for Microbiology Annual Meeting,
Orlando, FL, May 23, 2001.
- Vincent FC, Tibi AR, Darbord JC. A
bacterial biofilm in a hemodialysis system. Assessment of disinfection
and crossing of endotoxin. ASAIO Transactions 1989;35:310–3.
- Holland SP, Mathias RG, Morck DW, Chiu J, Slade SG. Diffuse
lamellar keratitis related to endotoxins released from sterilizer reservoir
biofilms. Opthalmology 2000;107:1227–34.
- Rioufol C, Devys C, Meunier G, Perraud M, Goullet D. Quantitative
determination of endotoxins released by bacterial biofilms. J Hosp
Infect 1999;43:203–9.
- Ward KH, Olson ME, Lam K, Costerton JW. Mechanisms
of persistent infection associated with peritoneal implants. J Med
Microbiol 1992;36:406–3.
- Shiau A-L, Wu C-L. The
inhibitory effect of Staphylococcus epidermidis slime on the
phagocytosis of murine peritoneal macrophages is interferon-independent.
Microbiol Immunol 1998;42:33–40.
- Meluleni GJ, Grout M, Evans DJ, Pier GB. 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;155:2029–38.
- Yasuda H, Ajiki Y, Aoyama J, Yokota T. Interaction
between human polymorphonuclear leucocytes and bacteria released from
in vitro bacterial biofilm models. J Med Microbiol 1994;41:359–67.
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