Evidence map›Paper›PMID 21986821›Full record

ArticleAntimicrobial agents and chemotherapy2012

Elevated cell wall chitin in Candida albicans confers echinocandin resistance in vivo.

Keunsook K Lee, Donna M Maccallum, Mette D Jacobsen, Louise A Walker, Frank C Odds, Neil A R Gow, Carol A Munro

Abstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers.

0numbers the graph read from it
0cells of the map it votes in
120citing papers in PubMed
7.6field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

120 citing papers in PubMed, 206 citations in OpenAlex.

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  17. Journal of fungi (Basel, Switzerland) · 2024
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  18. Microbiology and molecular biology reviews : MMBR · 2024
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  19. The Putative CytochromeJournal of fungi (Basel, Switzerland) · 2024
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  20. Article

60 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Keunsook K LeeSchool of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom.
Donna M Maccallum
Mette D Jacobsen
Louise A Walker
Frank C Odds
Neil A R Gow
Carol A Munro
University of Aberdeen · GB

Funding

Biotechnology and Biological Sciences Research Council BB/F00513X/1Medical Research Council G0400284Wellcome TrustWellcome Trust 080088Wellcome Trust 086827
6 · The paper itself

Abstract

Candida albicans cells with increased cell wall chitin have reduced echinocandin susceptibility in vitro. The aim of this study was to investigate whether C. albicans cells with elevated chitin levels have reduced echinocandin susceptibility in vivo. BALB/c mice were infected with C. albicans cells with normal chitin levels and compared to mice infected with high-chitin cells. Caspofungin therapy was initiated at 24 h postinfection. Mice infected with chitin-normal cells were successfully treated with caspofungin, as indicated by reduced kidney fungal burdens, reduced weight loss, and decreased C. albicans density in kidney lesions. In contrast, mice infected with high-chitin C. albicans cells were less susceptible to caspofungin, as they had higher kidney fungal burdens and greater weight loss during early infection. Cells recovered from mouse kidneys at 24 h postinfection with high-chitin cells had 1.6-fold higher chitin levels than cells from mice infected with chitin-normal cells and maintained a significantly reduced susceptibility to caspofungin when tested in vitro. At 48 h postinfection, caspofungin treatment induced a further increase in chitin content of C. albicans cells harvested from kidneys compared to saline treatment. Some of the recovered clones had acquired, at a low frequency, a point mutation in FKS1 resulting in a S645Y amino acid substitution, a mutation known to confer echinocandin resistance. This occurred even in cells that had not been exposed to caspofungin. Our results suggest that the efficacy of caspofungin against C. albicans was reduced in vivo due to either elevation of chitin levels in the cell wall or acquisition of FKS1 point mutations.

Indexed as

Amino Acid SubstitutionAnimalsAntifungal AgentsCandida albicansCandidiasisCaspofunginCell WallChitinDNA Mutational AnalysisDrug Resistance, FungalEchinocandinsFemaleFungal ProteinsGlucosyltransferasesKidneyLipopeptidesAntifungal AgentsCaspofunginChitinEchinocandinsFungal ProteinsGlucosyltransferasesLipopeptides

Identifiers

PMID21986821
PMCPMC3256049
OpenAlexW2127997803

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.