Biomedical Engineering Reference
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classical assays to address this question. Using their standard assay for biofilm
formation in conjunction with electron microscopy, they showed that C. albi-
cans biofilms became resistant to five antifungal compounds routinely used in
clinical settings (Hawser and Douglas 1995). This drug resistance phenotype
is often associated with bacterial biofilms. Furthermore, the observed increase
in antibiotic resistance could not be simply attributed to the decrease in
growth rate observed for fungi growing on surfaces (Baillie and Douglas 1998).
Another species of Candida , C. dubliniensis has the ability to adhere and
form biofilms with structural heterogeneity, typical microcolony, and water
channel architecture similar to that described for bacterial and C. albicans
biofilms (O'Toole et al. 2000b; Ramage et al. 2001). In addition, resistance of
C. dubliniensis to fluconazole, as well as its increased resistance to ampho-
tericin B treatment (Moran et al. 1998; Quindos et al. 2000; Martinez et al.
2002), were also demonstrated.
Other opportunistic biofilm-forming Candida species were also associated
with catheter-related bloodstream infections (CRBSIs) including C. parap-
silosis , C. tropicalis, C. lusitaniae, C. krusei , and C. glabrata (Hawser and
Islam 2006). Biofilm colonization of ventricular shunt catheters, peritoneal
dialysis fistulas, and cardiac valves by Crytococcus neoformans have also
been reported and are of particular concern in view of the growing use
of ventriculo-peritoneal shunts to manage intracranial hypertension associ-
ated with cryptococcal meningoencephalitis in immunocompromised patients.
Recurrent meningitis in patients with ventriculo-peritoneal shunts has also
been associated with biofilm colonization by Coccidioides immitis . Endocardi-
tis associated with infections of prosthetic valves and other cardiac devices
by Aspergillus species is a growing concern in immunocompromised patients,
although a definitive role of biofilms has yet to be established. Although Can-
dida and Aspergillus species are the etiological agents in only about 8% of
implant infections, they are emerging as dangerous pathogens affecting patient
survival rate in some settings of 50% (Anderson and Marchant 2000).
4.3.3 Microbial Interactions in Mixed-Species Biofilms
Data accumulating in the past few years on biofilms suggests that there seems
to be a specific “biofilm life mode” distinctive from the “planktonic life mode”
(Stoodley et al. 2002). It appears that biofilm development creates struc-
tured communities in which several different subpopulations may be present,
in spite of the fact that the cell population is isogenic (Tolker-Nielsen and
Molin 2000). These features are in accord with the assumption that biofilms
are bacterial analogues or a reflection of tissues. The observed heterogeneities
point toward putative phenotypic interactions between the different subpop-
ulations, in analogy with what is known from ecological studies on microbial
subpopulations in the environment.
In microbial biofilms most of the cells are present in the form of various
types of aggregates, with extremely small intercellular distances, creating ideal
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