ArticleBMC genomics2010
Chemogenomic and transcriptome analysis identifies mode of action of the chemosensitizing agent CTBT (7-chlorotetrazolo[5,1-c]benzo[1,2,4]triazine).
Article in BMC genomics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 24 citations in OpenAlex.
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- Glucosinolate-derived isothiocyanates impact mitochondrial function in fungal cells and elicit an oxidative stress response necessary for growth recovery.Frontiers in plant science · 2015Article
- Targeting the mitochondrial respiratory chain of Cryptococcus through antifungal chemosensitization: a model for control of non-fermentative pathogens.Molecules (Basel, Switzerland) · 2013Article
- Milbemycins: more than efflux inhibitors for fungal pathogens.Antimicrobial agents and chemotherapy · 2013Article
- Antifungal activity of fused Mannich ketones triggers an oxidative stress response and is Cap1-dependent in Candida albicans.PloS one · 2013Article
- Amino acid-derived 1,2-benzisothiazolinone derivatives as novel small-molecule antifungal inhibitors: identification of potential genetic targets.Antimicrobial agents and chemotherapy · 2012Article
- Yeast toxicogenomics: genome-wide responses to chemical stresses with impact in environmental health, pharmacology, and biotechnology.Frontiers in genetics · 2012Article
- Chemosensitization as a means to augment commercial antifungal agents.Frontiers in microbiology · 2012Article
- A genome-wide screen identifies yeast genes required for protection against or enhanced cytotoxicity of the antimalarial drug quinine.Molecular genetics and genomics : MGG · 2011Article
- Oxidative stress response and virulence factors in Candida glabrata clinical isolates.Folia microbiologica · 2011Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundCTBT (7-chlorotetrazolo [5,1-c]benzo[1,2,4]triazine) increases efficacy of commonly used antifungal agents by an unknown mechanism. It increases the susceptibility of Saccharomyces cerevisiae, Candida albicans and Candida glabrata cells to cycloheximide, 5-fluorocytosine and azole antimycotic drugs. Here we elucidate CTBT mode of action with a combination of systematic genetic and transcriptome analysis.
resultsTo identify the cellular processes affected by CTBT, we screened the systematic haploid deletion mutant collection for CTBT sensitive mutants. We identified 169 hypersensitive deletion mutants. The deleted genes encode proteins mainly involved in mitochondrial functions, DNA repair, transcription and chromatin remodeling, and oxidative stress response. We found that the susceptibility of yeast cells to CTBT depends on molecular oxygen. Transcriptome analysis of the immediate early response to CTBT revealed rapid induction of oxidant and stress response defense genes. Many of these genes depend on the transcription factors Yap1 and Cin5. Yap1 accumulates rapidly in the nucleus in CTBT treated cells suggesting acute oxidative stress. Moreover, molecular calculations supported a superoxide generating activity of CTBT. Superoxide production in vivo by CTBT was found associated to mitochondria as indicated by oxidation of MitoSOX Red.
conclusionWe conclude that CTBT causes intracellular superoxide production and oxidative stress in fungal cells and is thus enhancing antimycotic drug effects by a secondary stress.
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