Alfatah M~Arumugam P, 2019

Pubmed ID 31029968
Title Chemical-genetic interaction landscape of mono-(2-ethylhexyl)-phthalate using chemogenomic profiling in yeast.
Authors Mohammad Alfatah, Jin Huei Wong, Kiat Whye Kong, Felix Utama, Shawn Hoon, Prakash Arumugam
Abstract Integration of chemical-genetic interaction data with biological functions provides a mechanistic understanding of how toxic compounds affect cells. Mono-(2-ethylhexyl)-phthalate (MEHP) is an active metabolite of di-(2-ethylhexyl)-phthalate (DEHP), a commonly used plasticizer. MEHP adversely affects human health causing hepatotoxicity and reproductive toxicity. How MEHP affects cellular physiology is not fully understood. We utilized a genome-wide competitive fitness-based assay called 'chemogenomic profiling' to determine the genetic interaction map of MEHP in Saccharomyces cerevisiae. Gene Ontology enrichment analysis of 218 genes that provide resistance to MEHP indicated that MEHP affects seven cellular processes namely: (1) cellular amino acid biosynthetic process, (2) sterol biosynthetic process, (3) cellular transport, (4) transcriptional and translational regulation, (5) protein glycosylation, (6) cytokinesis and cell morphogenesis and (7) ionic homeostasis. We show that MEHP protects yeast cells from membrane perturbing agents such as amphotericin B, dihydrosphingosine and phytosphingosine. Moreover, we also demonstrate that MEHP compromises the integrity of the yeast plasma membrane and cell wall. Our work provides a basis for further investigation of MEHP toxicity in humans.
Citation Chemosphere 2019; 228:219-231


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Paper Phenotype Condition Medium Collection Tested mutants Data Details
Alfatah M~Arumugam P, 2019 growth (pooled culture, barseq) MEHP [2.3 mM] YPD, HEPES [25 mM], pH 6.8, DMSO hom 4,792 Quantitative

Curation history

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