Cited by 73Antifungal resistance and susceptibilityFungal Infections and StudiesFungal and yeast genetics research

In vivo imaging of disseminated murine Candida albicans infection reveals unexpected host sites of fungal persistence during antifungal therapy

Open access
Jacobsen, Ilse D., Lüttich, Anja, Kurzai, Oliver, Hube, Bernhard, Brock, Matthias·2014·Journal of Antimicrobial Chemotherapy

Abstract

OBJECTIVES: Candida albicans is an important fungal pathogen that can cause life-threatening disseminated infections. To determine the efficacy of therapy in murine models, a determination of renal fungal burden as cfu is commonly used. However, this approach provides only a snapshot of the current situation in an individual animal and cryptic sites of infection may easily be missed. Thus, we aimed to develop real-time non-invasive imaging to monitor infection in vivo. METHODS: Bioluminescent C. albicans reporter strains were developed based on a bioinformatical approach for codon optimization. The reporter strains were analysed in vitro and in vivo in the murine model of systemic candidiasis. RESULTS: Reporter strains allowed the in vivo monitoring of infection and a determination of fungal burden, with a high correlation between bioluminescence and cfu count. We confirmed the kidney as the main target organ but additionally observed the translocation of C. albicans to the urinary bladder. The treatment of infected mice with caspofungin and fluconazole significantly improved the clinical outcome and clearance of C. albicans from the kidneys; however, unexpectedly, viable fungal cells persisted in the gall bladder. Fungi were secreted with bile and detected in the faeces, implicating the gall bladder as a reservoir for colonization by C. albicans after antifungal therapy. Bile extracts significantly decreased the susceptibility of C. albicans to various antifungals in vitro, thereby probably contributing to its persistence. CONCLUSIONS: Using in vivo imaging, we identified cryptic sites of infection and persistence of C. albicans in the gall bladder during otherwise effective antifungal treatment. Bile appears to directly interfere with antifungal activity.

Integrity signals

Registry

Crossref · 10.1093/jac/dku198

Cites

56 of 56 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

  • In a murine model of systemic C. albicans infection, antifungal treatment achieved substantial eradication of fungal cells, but persistent pathogen reservoirs were consistently detected in gallbladder tissue during long-term monitoring.

    “Another investigation utilizing a murine model of systemic C. albicans infection demonstrated that although antifungal treatment achieved substantial eradication of fungal cells, persistent pathogen reservoirs were consistently detected in gallbladder tissue during long-term monitoring [48].”

    From Antifungal persistence: Clinical relevance and mechanisms (2025) · cites this paper as [48]

  • Antifungal persistence has been observed in vivo in a few studies using animal models.

    “Antifungal persistence has been observed in vivo in a few studies using animal models [3,39,48].”

    From Antifungal persistence: Clinical relevance and mechanisms (2025) · cites this paper as [48]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Jacobsen, I. D., Lüttich, A., Kurzai, O., Hube, B., & Brock, M.
Affiliations
  • Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V. - Hans-Knöll-Institut (HKI) (DE)
  • Jena University Hospital (DE)
Corresponding author
Brock, Matthias
Venue
Journal of Antimicrobial Chemotherapy
Published
2014-06-20
Volume
69
Issue
10
Pages
2785-2796
ISSN
  • 0305-7453 (ISSN-L)
  • 1460-2091
OpenAlex
W1974204295
Cited by
73
References
56
Citations by year
2026: 5 · 2025: 5 · 2024: 2 · 2023: 4 · 2022: 5 · 2021: 5 · 2020: 7 · 2019: 7 · 2018: 9 · 2017: 9 · 2016: 3 · 2015: 10 · 2014: 2
FWCI
5.65
Type
journal article
Language
en
Licence
cc-by
Locations
  • Journal of Antimicrobial Chemotherapy (publishedVersion)
  • PubMed (publishedVersion)
  • Repository@Nottingham (University of Nottingham) (submittedVersion, cc-by)
  • Repository@Nottingham (University of Nottingham) (submittedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
Bundesministerium für Bildung und Forschung
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Keywords
Candida albicans, systemic candidiasis, in vivo imaging, bioluminescent reporter strain, codon optimization, fungal persistence, bile, antifungal resistance, caspofungin, fluconazole, pyelonephritis
MeSH terms
Animals, Antifungal Agents, Candida albicans, Candidiasis, Diagnostic Imaging, Disease Models, Animal, Female, Luminescent Measurements, Microbial Sensitivity Tests, Organ Specificity, Colony Count, Microbial, Gene Expression, Genes, Reporter, Mice, Molecular Imaging

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review