Trends in Microbiology
Candida biofilms and their role in infection
Section snippets
Candida infections and biofilms
A relatively small number of Candida species are pathogenic for humans. These organisms are capable of causing a variety of superficial and deep-seated mycoses that are distributed worldwide. All are opportunistic pathogens, liable to attack immunocompromised hosts or those debilitated in some other way. The principal pathogen of the genus is the fungus responsible for thrush, Candida albicans, which can grow either as oval budding yeasts, as continuous septate hyphae or as pseudohyphae; all of
Model biofilm systems
Various model systems (Table 1) have been used to characterize the overall properties of Candida biofilms [21]. Almost all of these have been adapted from methods reported previously for bacteria. The simplest, and the first to be described, involves growing adherent populations on the surfaces of small discs cut from catheters 21, 22, 23. Growth is monitored quantitatively by a colourimetric assay that depends on the reduction of a tetrazolium salt, or by [3H]leucine incorporation; both
Biofilm ultrastructure
One distinguishing feature of C. albicans biofilms is the mixture of morphological forms usually present. Biofilm development on catheter discs was first examined by scanning electron microscopy, which showed that initial attachment of yeast cells was followed, after 3–6 hours, by germ-tube formation. Fully mature biofilms, produced after incubation for up to 48 hours, consisted of a dense network of yeasts, hyphae and pseudohyphae [22]. Hyphal forms were not seen when the organism was grown in
Drug resistance of biofilms
Microbial biofilms are notoriously resistant to a variety of antimicrobial agents, including antibiotics, antiseptics and industrial biocides. For example, when bacteria exist in the biofilm form they are 10–1000 times more resistant to antibiotics than are planktonic cells [6]. Corresponding resistance of Candida biofilms to antifungal agents was first demonstrated in 1995 [23]. A catheter disc assay was used to determine drug concentrations that caused a 50% inhibition of metabolic activity
Possible mechanisms of drug resistance
The mechanisms of biofilm resistance to antimicrobial agents are not fully understood. Possible mechanisms include: (1) restricted penetration of drugs through the biofilm matrix; (2) phenotypic changes resulting from a decreased growth rate or nutrient limitation; and (3) expression of resistance genes induced by contact with a surface 3, 6. Another recent suggestion is that a small number of ‘persister’ cells are responsible for resistance [46]. Multiple mechanisms appear to operate in
Mixed fungal–bacterial biofilms
Bacteria are often found with Candida species in polymicrobial biofilms in vivo, and it is likely that extensive interspecies interactions take place in these adherent populations. In vitro, the catheter disc model system has been used to investigate mixed-species biofilms consisting of C. albicans and Staphylococcus epidermidis, the commonest agent of bacterial catheter-related infection. Two strains of S. epidermidis were used: a slime-producing wild-type and a slime-negative mutant. Scanning
Future perspectives
Although biofilm research on fungi has lagged well behind that on bacteria, the basic structural features and properties of C. albicans biofilms have been established. Rather more remains to be determined about biofilms formed by the non-C. albicans species. With the sequencing of the C. albicans genome and the advent of DNA microarray technology, research in the immediate future is likely to concentrate on defining the biofilm phenotype of C. albicans with a view to identifying possible
Acknowledgements
I would like to thank Drs George Baillie and Stephen Hawser for their major contributions to biofilm work in Glasgow over a number of years.
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