Trends in Microbiology
Volume 11, Issue 1, January 2003, Pages 30-36
Journal home page for Trends in Microbiology

Candida biofilms and their role in infection

https://doi.org/10.1016/S0966-842X(02)00002-1Get rights and content

Abstract

Pathogenic fungi in the genus Candida can cause both superficial and serious systemic disease, and are now recognized as major agents of hospital-acquired infection. Many Candida infections involve the formation of biofilms on implanted devices such as indwelling catheters or prosthetic heart valves. Biofilms of Candida albicans formed in vitro on catheter material consist of matrix-enclosed microcolonies of yeasts and hyphae, arranged in a bilayer structure. The biofilms are resistant to a range of antifungal agents currently in clinical use, including amphotericin B and fluconazole, and there appear to be multiple resistance mechanisms. Recent studies with mixed biofilms containing Candida and bacterial species suggest that extensive and striking interactions occur between the prokaryotic and eukaryotic cells in these adherent populations.

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.

References (55)

  • R.M. Donlan et al.

    Biofilms: survival mechanisms of clinically relevant microorganisms

    Clin. Microbiol. Rev.

    (2002)
  • J.W. Costerton

    Bacterial biofilms: a common cause of persistent infections

    Science

    (1999)
  • H.F. Jenkinson et al.

    Interactions between Candida species and bacteria in mixed infections

  • Lappin-Scott, H.M., Costerton, J.W., eds, (1995) Microbial Biofilms, Cambridge University...
  • Allison, D.G. et al., eds, (2000) Community Structure and Co-operation in Biofilms, Cambridge University...
  • F.C. Odds

    Candida and Candidosis

    (1988)
  • R.A. Calderone

    Introduction and historical perspectives

  • J.A. Crump et al.

    Intravascular catheter-associated infections

    Eur. J. Clin. Microbiol. Infect. Dis.

    (2000)
  • D.G. Maki et al.

    Engineering out the risk of infection with urinary catheters

    Emerg. Infect. Dis.

    (2001)
  • C.G. Adair

    Implications of endotracheal tube biofilm ventilator-associated pneumonia

    Intensive Care Med.

    (1999)
  • D.A. Goldmann et al.

    Pathogenesis of infections related to intravascular catheterization

    Clin. Microbiol. Rev.

    (1993)
  • Sherertz, R.J. (2000) Pathogenesis of vascular catheter infection. In Infections Associated with Indwelling Medical...
  • B.J. Kullberg et al.

    Candidemia

  • E. Budtz-Jorgensen

    Candida-associated denture stomatitis and angular cheilitis

  • H.C. Van der Mei

    Effect of probiotic bacteria on prevalence of yeasts in oropharyngeal biofilms on silicone rubber voice prostheses in vitro

    J. Med. Microbiol.

    (2000)
  • S.P. Hawser et al.

    Biofilm formation by Candida species on the surface of catheter materials in vitro

    Infect. Immun.

    (1994)
  • S.P. Hawser et al.

    Resistance of Candida albicans biofilms to antifungal agents in vitro

    Antimicrob. Agents Chemother.

    (1995)
  • Cited by (965)

    View all citing articles on Scopus
    View full text