ArticleAntimicrobial agents and chemotherapy2012
Fks1 and Fks2 are functionally redundant but differentially regulated in Candida glabrata: implications for echinocandin resistance.
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 86 papers.
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.
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.
Who cites it
86 citing papers in PubMed, 143 citations in OpenAlex.
- Slt2 kinase of the cell wall integrity pathway is required for Fks2-specific echinocandin resistance inMicrobiology spectrum · 2026Article
- Antifungal susceptibility, FKS1 gene expression, and virulence determinants of Candida albicans in pediatric and neonatal candidiasis.BMC infectious diseases · 2026Article
- Uncovering actionable trade-offs of antifungal resistance in a yeast pathogen.Molecular systems biology · 2026Article
- A Calcineurin Inhibitor as an Enhancer ofACS omega · 2026Article
- Inhibition mechanism of the fungal β-1,3-glucan synthases by triterpenoid antifungal drugs.Nature communications · 2026Article
- Echinocandin tolerance and persistencemBio · 2026Article
- Natural product based approaches to overcomeFrontiers in antibiotics · 2026Review
- Community-Onset Fungemias: Epidemiology and Genomic Characterization at a Tertiary-Care Hospital in Barcelona, Spain.Journal of fungi (Basel, Switzerland) · 2025Article
- Molecular landscape of the fungal plasma membrane and implications for antifungal action.Nature communications · 2025Article
- Antifungal resistance: Emerging mechanisms and implications (Review).Molecular medicine reports · 2025Review
- Expression of 1,3-β-glucan synthase subunits inAntimicrobial agents and chemotherapy · 2025Article
- Tn-seq screens inmSphere · 2025Article
- Targeting epigenetic regulators to overcome drug resistance in the emerging human fungal pathogen Candida auris.Nature communications · 2025Article
- The Gcn5 lysine acetyltransferase mediates cell wall remodeling, antifungal drug resistance, and virulence ofmSphere · 2025Article
- Hotspot gene conversion between FKS1 and FKS2 in echinocandin resistant Candida glabrata serial isolates.npj antimicrobials and resistance · 2025Article
- Cryo-EM structure of the β-1,3-glucan synthase FKS1-Rho1 complex.Nature communications · 2025Article
- Antifungal drug resistance in Candida glabrata: role of cellular signaling and gene regulatory networks.FEMS yeast research · 2025Review
- Mechanisms of multidrug resistance caused by an Ipi1 mutation in the fungal pathogen Candida glabrata.Nature communications · 2025Article
- Transposon-sequencing (Tn-seq) of the Candida glabrata reference strain CBS138 reveals epigenetic plasticity, structural variation, and intrinsic mechanisms of resistance to micafungin.G3 (Bethesda, Md.) · 2024Article
- Genomic description of acquired fluconazole- and echinocandin-resistance in patients with serialJournal of clinical microbiology · 2024Article
26 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
The echinocandins caspofungin, micafungin, and anidulafungin, inhibitors of cell wall β-1,3-glucan synthesis, were recently elevated to first-line agents for treating infections due to the azole-refractory yeast Candida glabrata. In Candida albicans, echinocandin resistance is strictly associated with mutations in Fks1, a large integral membrane protein and putative β-1,3-glucan synthase, while mutations in both Fks1 and its paralog Fks2 (but not Fks3) have been associated with resistance in C. glabrata. To further explore their function, regulation, and role in resistance, C. glabrata fks genes were disrupted and subjected to mutational analysis, and their differential regulation was explored. An fks1Δ fks2Δ double disruptant was not able to be generated; otherwise, all three single and remaining two double disruptants displayed normal growth and echinocandin susceptibility, indicating Fks1-Fks2 redundancy. Selection on echinocandin-containing medium for resistant mutants was dependent on strain background: only fks1Δ and fks1Δ fks3Δ strains consistently yielded mutants exhibiting high-level resistance, all with Fks2 hot spot 1 mutations. Thus, Fks1-Fks2 redundancy attenuates the rate of resistance; further analysis showed that it also attenuates the impact of resistance-conferring mutations. Growth of the fks1Δ and, especially, fks1Δ fks3Δ strains was specifically susceptible to the calcineurin inhibitor FK506. Relatedly, FK506 addition or calcineurin gene CMP2 disruption specifically reversed Fks2-mediated resistance of laboratory mutants and clinical isolates. RNA analysis suggests that transcriptional control is not the sole mechanism by which calcineurin modulates Fks2 activity.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.