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Cited by 389Antifungal resistance and susceptibilityBacterial biofilms and quorum sensingFungal and yeast genetics research

Development and Characterization of an In Vivo Central Venous Catheter Candida albicans Biofilm Model

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Andes, D., Nett, J., Oschel, P., Albrecht, R., Marchillo, K., Pitula, A.·2004·Infection and Immunity
DOI 10.1128/iai.72.10.6023-6031.2004PMC PMC517581
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Abstract

Biofilms represent a niche for microorganisms where they are protected from both the host immune system and antimicrobial therapies. Biofilm growth serves as an increasing source of clinical infections. Candida infections are difficult to manage due to their persistent nature and associated drug resistance. Observations made in biofilm research have generally been limited to in vitro models. Using a rat central venous catheter model, we characterized in vivo Candida albicans biofilm development. Time-course quantitative culture demonstrated a progressive increase in the burden of viable cells for the first 24 h of development. Fluorescence and scanning electron microscopy revealed a bilayered architecture. Adjacent to the catheter surface, yeast cells were densely embedded in an extracellular matrix. The layer adjacent to the catheter lumen was less dense. The outermost surface of the biofilm contained both yeast and hyphal forms, and the extracellular material in which they were embedded appeared fibrous. These architectural features were similar in many respects to those described for in vitro models. However, scanning electron microscopy also revealed host cells embedded within the biofilm matrix. Drug susceptibility was determined by using two assays and demonstrated a biofilm-associated drug resistance phenotype. The first assay demonstrated continued growth of cells in the presence of supra-MIC antifungal drug concentrations. The second assay demonstrated reduced susceptibility of biofilm-grown cells following removal from the biofilm structure. Lastly, the model provided sufficient nucleic material for study of differential gene expression associated with in vivo biofilm growth. Two fluconazole efflux pumps, CDR1 and CDR2 , were upregulated in the in vivo biofilm-associated cells. Most importantly, the studies described provide a model for further investigation into the molecular mechanisms of C. albicans biofilm biology and drug resistance. In addition, the model provides a means to study novel drug therapies and device technologies targeted to the control of biofilm-associated infections.

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Crossref · 10.1128/iai.72.10.6023-6031.2004

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  • The rat central venous catheter infection model is well-established.

    “A well-established rat central venous catheter infection model (32) was used for in vivo biofilm modeling to mimic human catheter infections as described previously (32).”

    From A Histone Deacetylase Complex Mediates Biofilm Dispersal and Drug Resistance in Candida albicans (2014) · cites this paper as [32]

  • The rat central venous catheter infection model mimics human catheter infections.

    “A well-established rat central venous catheter infection model (32) was used for in vivo biofilm modeling to mimic human catheter infections as described previously (32).”

    From A Histone Deacetylase Complex Mediates Biofilm Dispersal and Drug Resistance in Candida albicans (2014) · cites this paper as [32]

  • No sex bias has been observed in the rat external jugular venous catheter biofilm model.

    “Experiments were conducted using male rats as no sex bias has been observed in this model, thus reducing the extraneous use of animals82,83.”

    From Adhesin Als4112 promotes Candida auris skin colonization through interactions with keratinocytes and extracellular matrix proteins (2025) · cites this paper as [82]

  • While under treatment with antifungals, biofilm cells up-regulate these transporters within six hours of surface contact both in vitro and in vivo, even in the absence of drug.

    “While under treatment with antifungals, biofilm cells up-regulate these transporters within six hours of surface contact both in vitro and in vivo, even in the absence of drug [136,137,138,139].”

    From Candida glabrata Biofilms: How Far Have We Come? (2017) · cites this paper as [139]

  • Biofilm architectures in rat and rabbit central venous and indwelling urinary catheter models and in rat denture stomatitis models include numerous yeast cells in the basal region, and hyphae and extracellular matrix extending throughout the biofilm.

    “Biofilm architectures in rat and rabbit central venous and indwelling urinary catheter models and in rat denture stomatitis models also include numerous yeast cells in the basal region, and hyphae and extracellular matrix extending throughout the biofilm (5, 84, 131, 134, 166, 173, 199).”

    From <i>Candida albicans</i> Biofilms and Human Disease (2015) · cites this paper as [5]

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Authors
Andes, D., Nett, J., Oschel, P., Albrecht, R., Marchillo, K., & Pitula, A.
Affiliations
  • Department of Medicine
  • Biological and Biomaterials Preparation, Imaging, and Characterization Laboratory, Department of Animal Science, University of Wisconsin, Madison, Wisconsin
  • University of Wisconsin–Madison (US)
ORCID
Venue
Infection and Immunity
Publisher
American Society for Microbiology
Published
2004-10
Volume
72
Issue
10
Pages
6023-6031
ISSN
  • 0019-9567 (ISSN-L)
  • 1098-5522
DOI
10.1128/iai.72.10.6023-6031.2004
PMC
PMC517581
OpenAlex
W2149218811
Cited by
389
References
62
Citations by year
2026: 10 · 2025: 8 · 2024: 12 · 2023: 18 · 2022: 16 · 2021: 12 · 2020: 13 · 2019: 15 · 2018: 22 · 2017: 28 · 2016: 28 · 2015: 26 · 2014: 23 · 2013: 19 · 2012: 21
FWCI
6.81
Type
journal article
Language
en
Open access
Licence
journals.asm.org/non-commercial-tdm-license (tdm)
Locations
  • Infection and Immunity (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute of Allergy and Infectious Diseases (K08AI001767, R01AI073289)
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, central venous catheters, catheter-related infection, antifungal resistance, extracellular matrix, CDR1, CDR2, gene expression, biofilm structure
MeSH terms
Animals, Candida albicans, Candidiasis, Catheterization, Central Venous, Female, Genes, Fungal, Kidney, RNA, Fungal, RNA, Messenger, Sonication, Time Factors, Transcription, Genetic, Fluconazole, Gene Expression Regulation, Fungal, Rats, Sprague-Dawley, Biofilms, Microscopy, Confocal, Models, Animal, Drug Resistance, Fungal, Hyphae, Rats

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