Mechanisms of Candida Biofilm Drug Resistance
Open accessAbstract
Candida commonly adheres to implanted medical devices, growing as a resilient biofilm capable of withstanding extraordinarily high antifungal concentrations. As currently available antifungals have minimal activity against biofilms, new drugs to treat these recalcitrant infections are urgently needed. Recent investigations have begun to shed light on the mechanisms behind the profound resistance associated with the biofilm mode of growth. This resistance appears to be multifactorial, involving both mechanisms similar to conventional, planktonic antifungal resistance, such as increased efflux pump activity, as well as mechanisms specific to the biofilm lifestyle. A unique biofilm property is the production of an extracellular matrix. Two components of this material, β-glucan and extracellular DNA, promote biofilm resistance to multiple antifungals. Biofilm formation also engages several stress response pathways that impair the activity of azole drugs. Resistance within a biofilm is often heterogeneous, with the development of a subpopulation of resistant persister cells. In this article we review the molecular mechanisms underlying Candida biofilm antifungal resistance and their relative contributions during various growth phases.
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Candida biofilms cause a temporary physiological change in drug responses.
“Candida spp. biofilms induce a transient, physiological alteration in drug responses22 (Box 3); that is, fungal biofilms exhibit reduced antifungal drug susceptibility via mechanisms that are dependent on cells growing within a biofilm, in which cells adhere to a substrate and form a thick mat of cells and secreted extracellular matrix that holds them together and reduces drug efficacy.”
From Drug resistance and tolerance in fungi. (2020) · cites this paper as [22]
Fungal biofilms are less susceptible to antifungals through mechanisms requiring biofilm growth, with cells adhering to a surface and forming a dense mat plus secreted matrix that lowers drug efficacy.
“Candida spp. biofilms induce a transient, physiological alteration in drug responses22 (Box 3); that is, fungal biofilms exhibit reduced antifungal drug susceptibility via mechanisms that are dependent on cells growing within a biofilm, in which cells adhere to a substrate and form a thick mat of cells and secreted extracellular matrix that holds them together and reduces drug efficacy.”
From Drug resistance and tolerance in fungi. (2020) · cites this paper as [22]
C. albicans biofilms are resistant to standard antifungal drugs.
“C. albicans biofilms are resistant to standard antifungal drugs; not only do biofilms provide physical protection from drugs, cells in biofilms become intrinsically resistant to antimicrobial compounds because of their altered metabolic states and their constitutive upregulation of drug efflux pumps (7–10).”
From A Histone Deacetylase Complex Mediates Biofilm Dispersal and Drug Resistance in Candida albicans (2014) · cites this paper as [10]
Several general mechanisms of biofilm drug resistance are thought to confer resistance to multiple classes of antifungals in Candida species biofilms: up-regulation of efflux pumps, cell wall composition, increased cell density and quorum sensing effect, presence of an extracellular matrix, changes in metabolism, presence of persister cells, and cellular signalling and stress responses.
“Several general mechanisms of biofilm drug resistance are thought to confer resistance to multiple classes of antifungals in Candida species biofilms: the up-regulation of efflux pumps, cell wall composition, increased cell density and quorum sensing effect, presence of an extracellular matrix, changes in metabolism, the presence of persister cells, and cellular signalling and stress responses [”
From Candida glabrata Biofilms: How Far Have We Come? (2017) · cites this paper as [132]
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References 136 · Cited by 422
Research works printed but not linked: 3
- [60]Tobudic S Kratzer C Lassnigg A Graninger W Presterl E In vitro activity of antifungal combinations against Candida albicans biofilms J Antimicrob Chemother 65 2 271 274 2010 19996142
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- Authors
- Taff, H. T., Mitchell, K. F., Edward, J. A., & Andes, D. R.
- Affiliations
- University of Wisconsin–Madison (US)
- Venue
- Future Microbiology
- Publisher
- Informa UK Limited
- Published
- 2013-09-24
- Volume
- 8
- Issue
- 10
- Pages
- 1325-1337
- ISSN
- 1746-0913 (ISSN-L)
- 1746-0921
- PMC
- PMC3859465
- OpenAlex
- W2118355092
- Cited by
- 422
- References
- 136
- Citations by year
- 2026: 47 · 2025: 35 · 2024: 35 · 2023: 37 · 2022: 29 · 2021: 41 · 2020: 46 · 2019: 25 · 2018: 25 · 2017: 37 · 2016: 28 · 2015: 20 · 2014: 16
- FWCI
- 2.76
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Future Microbiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (T32GM008692)
- National Institute of Allergy and Infectious Diseases (R01AI073289)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
- Keywords
- Candida, biofilm, antifungal resistance, efflux pumps, extracellular matrix, β-glucan, extracellular DNA, stress response pathways, azole resistance, persister cells, biofilm heterogeneity, biomedical implants, fungal infection
- MeSH terms
- Animals, Antifungal Agents, Candida, Candidiasis, Humans, Biofilms, Drug Resistance, Fungal
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