Cited by 1,057Antifungal resistance and susceptibilityBacterial biofilms and quorum sensingFungal and yeast genetics research

The DOI matches its Crossref record; 215 of the 215 references it cites were found in a registry or an index; 6 of the 170 sources its claims cite were checked for support.

Candida albicans Biofilms and Human Disease

Open access
Nobile, Clarissa J., Johnson, Alexander D.·2015·Annual Review of Microbiology

Abstract

In humans, microbial cells (including bacteria, archaea, and fungi) greatly outnumber host cells. Candida albicans is the most prevalent fungal species of the human microbiota; this species asymptomatically colonizes many areas of the body, particularly the gastrointestinal and genitourinary tracts of healthy individuals. Alterations in host immunity, stress, resident microbiota, and other factors can lead to C. albicans overgrowth, causing a wide range of infections, from superficial mucosal to hematogenously disseminated candidiasis. To date, most studies of C. albicans have been carried out in suspension cultures; however, the medical impact of C. albicans (like that of many other microorganisms) depends on its ability to thrive as a biofilm, a closely packed community of cells. Biofilms are notorious for forming on implanted medical devices, including catheters, pacemakers, dentures, and prosthetic joints, which provide a surface and sanctuary for biofilm growth. C. albicans biofilms are intrinsically resistant to conventional antifungal therapeutics, the host immune system, and other environmental perturbations, making biofilm-based infections a significant clinical challenge. Here, we review our current knowledge of biofilms formed by C. albicans and closely related fungal species.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

This review summarizes how *Candida albicans* forms biofilms on medical devices and mucosal surfaces, and how these communities resist antifungal drugs and host defenses. It highlights a six-regulator transcriptional network, matrix- and persister-mediated drug resistance, and the clinical burden of biofilm infections.

Key findings

  • *C. albicans* biofilm development proceeds through four stages: adherence of yeast cells, proliferation into a basal layer, growth of pseudohyphae/hyphae with extracellular matrix production, and dispersal of yeast-form cells. Mature biofilms typically form within 24 hours in vitro.
  • Six master transcriptional regulators (Efg1, Tec1, Bcr1, Ndt80, Brg1, Rob1) are each required for biofilm development in vitro and in rat catheter/denture models; together they directly bind and likely regulate approximately 1,000 target genes. The review counts 50 transcriptional regulators and 101 nonregulatory genes with functionally validated biofilm roles.
  • Biofilm resistance involves early and sustained efflux pump upregulation, extracellular matrix components including β-1,3-glucan and extracellular DNA, and metabolically dormant persister cells. Matrix composition is reported as ~55% proteins/glycoproteins, 25% carbohydrates, 15% lipids, and 5% nucleic acids, with over 500 proteins identified.
  • Clinical impact: NIH estimates biofilms account for over 80% of microbial infections in the United States; CTG clade species account for 15% of hospital-acquired sepsis and are the fourth most frequent cause of bloodstream infections; over 5 million central venous catheters are placed annually in the United States (1992–2001 data), with biofilm infection in over 50%; estimated 100,000 deaths and $6.5 billion in excess expenditure annually in the United States; disseminated candidiasis mortality approaches 40% in some cases.

Methods

  • Narrative review of published literature on *C. albicans* and related fungal biofilms; no new experimental data are reported.
  • Synthesizes in vitro biofilm models (e.g., silicone squares, flow cells), in vivo/ex vivo animal models (rat/rabbit catheter, denture stomatitis, vaginal mucosal, bioluminescence), and genetic/genomic/proteomic studies (knockout screens, transcriptional profiling, proteomics).
  • Main analysis is qualitative synthesis, including tables of 50 transcriptional regulators and 101 nonregulatory genes with validated biofilm roles.

Limitations

  • Stated: little is known about persister cell formation and regulation; virtually nothing is known about interactions among *Candida* species in polymicrobial biofilms; the majority of newly identified biofilm-network target genes remain unstudied; the biofilm network outline is “undoubtedly incomplete”; and biofilm formation is often loosely defined in non-*Candida* fungi.
  • Evident: as a review, it does not present primary experimental data, and its conclusions depend on the designs and conditions of cited studies; many mechanistic findings come from in vitro models or non-*C. albicans* species.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1146/annurev-micro-091014-104330

Cites

215 of 215 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

83 Not checked yet · 20 Own interpretation · 11 No basis given · 2 Partly supported · 1 Supported · 1 Own result · accuracy not yet measured

Verify all 164 references — free account

Show all 67 claims

  • It may state two separate claims as one. 38
  • Probably not a substantial claim. 20
51 of 51
  • The paper relies on this without support.

    Virtually nothing is known about the interactions among Candida species in polymicrobial biofilms.

    “We know virtually nothing about the interactions among these Candida species in polymicrobial biofilms.”
  • The paper relies on this without support.

    No biofilm-specific drugs exist today for Candida albicans or any microbe.

    “No biofilm-specific drugs exist today for C. albicans (or any microbe), making treatment of biofilm-based infections particularly problematic.”
  • The paper relies on this without support.

    Candida albicans is the fungal pathogen most frequently isolated from human infections.

    “Although C. albicans is the fungal pathogen most frequently isolated from human infections”
  • The paper relies on this without support.

    Microbial infections are often thought of, and treated, as if a single microbial species were acting alone.

    “Microbial infections are often thought of, and treated, as if a single microbial species were acting alone.”
  • The paper relies on this without support.

    Keratitis is generally thought of as a biofilm infection and has been associated with the use of contact lenses.

    “Keratitis is generally thought of as a biofilm infection and has been associated with the use of contact lenses.”
5 of 5

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Citations

Cites

Show all 215 references

Research works printed but not linked: 5

  1. Dominic RM, 2007, Kathmandu Univ. Med. J., 5, 431
  2. Douglas LJ, 2002, Rev. Iberoamericana Micol., 19, 139
  3. Kolter R, 2010, Int. Microbiol., 13, 1
  4. Kullberg BJ, 2002, Eur. J. Med. Res., 7, 183
  5. Melo AS, 2006, Genet. Mol. Res., 5, 664

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Metadata

Authors
Nobile, C. J., & Johnson, A. D.
Affiliations
  • University of California, Merced (US)
  • University of California, San Francisco (US)
Venue
Annual Review of Microbiology
Published
2015-10-15
Volume
69
Issue
1
Pages
71-92
ISSN
  • 0066-4227 (ISSN-L)
  • 1545-3251
OpenAlex
W2170764510
Cited by
1,057
References
215
Citations by year
2026: 77 · 2025: 106 · 2024: 130 · 2023: 88 · 2022: 138 · 2021: 135 · 2020: 117 · 2019: 91 · 2018: 76 · 2017: 68 · 2016: 28 · 2015: 2
FWCI
8.81
Type
journal article
Language
en
Open access
Locations
  • Annual Review of Microbiology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • National Institutes of Health
  • National Institute of Allergy and Infectious Diseases (R00AI100896, R01AI083311, T32AI060537)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Keywords
Candida albicans, biofilm, candidiasis, fungal infection, human microbiota, antifungal resistance, host immune response, biomedical implants, biofilm-associated infections, mucosal candidiasis, systemic candidiasis, fungal communities
MeSH terms
Animals, Candida albicans, Candidiasis, Cell Adhesion, Fungi, Humans, Mycoses, Biofilms

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