Yeast ABC transporters in lipid trafficking

Prasad, Rajendra; Khandelwal, Nitesh; Banerjee, Atanu

doi:10.1016/j.fgb.2016.05.008

Cited by 29 publications

(23 citation statements)

References 92 publications

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“…Several A TP- b inding c assette (ABC) transporters that catalyze the ATP-dependent active solute transport across cell membranes in yeasts are associated with multidrug/multixenobiotic resistance (MDR/MXR) ( Jungwirth and Kuchler, 2006 ; Monk and Goffeau, 2008 ; Piecuch and Obłak, 2014 ). Although these transporters are usually considered drug/xenobiotic pumps, evidence is arising supporting the idea that their involvement in MDR/MXR may result from their specific and, in general, not yet determined biological role in the active transport of physiological substrates ( Prasad and Panwar, 2004 ; Cabrito et al, 2011 ; Prasad et al, 2016 ; Godinho et al, 2018 ). Moreover, the presence of a large number of ABC transporters involved in MDR/MXR in the genomes of yeasts and other organisms, from bacteria to man, also strongly suggests that these transporters may play important physiological roles even in the absence of the cytotoxic compounds to which they confer resistance.…”

Section: Introductionmentioning

confidence: 99%

The Paralogous Genes PDR18 and SNQ2, Encoding Multidrug Resistance ABC Transporters, Derive From a Recent Duplication Event, PDR18 Being Specific to the Saccharomyces Genus

et al. 2018

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Pleiotropic drug resistance (PDR) family of ATP-binding cassette (ABC) transporters play a key role in the simultaneous acquisition of resistance to a wide range of structurally and functionally unrelated cytotoxic compounds in yeasts. Saccharomyces cerevisiae Pdr18 was proposed to transport ergosterol at the plasma membrane, contributing to the maintenance of adequate ergosterol content and decreased levels of stress-induced membrane disorganization and permeabilization under multistress challenge leading to resistance to ethanol, acetic acid and the herbicide 2,4-D, among other compounds. PDR18 is a paralog of SNQ2, first described as a determinant of resistance to the chemical mutagen 4-NQO. The phylogenetic and neighborhood analysis performed in this work to reconstruct the evolutionary history of ScPDR18 gene in Saccharomycetaceae yeasts was focused on the 214 Pdr18/Snq2 homologs from the genomes of 117 strains belonging to 29 yeast species across that family. Results support the idea that a single duplication event occurring in the common ancestor of the Saccharomyces genus yeasts was at the origin of PDR18 and SNQ2, and that by chromosome translocation PDR18 gained a subtelomeric region location in chromosome XIV. The multidrug/multixenobiotic phenotypic profiles of S. cerevisiae pdr18Δ and snq2Δ deletion mutants were compared, as well as the susceptibility profile for Candida glabrata snq2Δ deletion mutant, given that this yeast species has diverged previously to the duplication event on the origin of PDR18 and SNQ2 genes and encode only one Pdr18/Snq2 homolog. Results show a significant overlap between ScSnq2 and CgSnq2 roles in multidrug/multixenobiotic resistance (MDR/MXR) as well as some overlap in azole resistance between ScPdr18 and CgSnq2. The fact that ScSnq2 and ScPdr18 confer resistance to different sets of chemical compounds with little overlapping is consistent with the subfunctionalization and neofunctionalization of these gene copies. The elucidation of the real biological role of ScSNQ2 will enlighten this issue. Remarkably, PDR18 is only found in Saccharomyces genus genomes and is present in almost all the recently available 1,000 deep coverage genomes of natural S. cerevisiae isolates, consistent with the relevant encoded physiological function.

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Section: Introductionmentioning

confidence: 99%

The Paralogous Genes PDR18 and SNQ2, Encoding Multidrug Resistance ABC Transporters, Derive From a Recent Duplication Event, PDR18 Being Specific to the Saccharomyces Genus

et al. 2018

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“…ABC transporters act as drug efflux pumps in Candida glabrata, as well as in the related yeasts Saccharomyces cerevisiae and Candida albicans. Additional members of the ABC transporter family play a role in lipid homeostasis, which may also influence antifungal treatment, as the drug targets are influenced by lipid content in the cell (1).…”

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confidence: 99%

Relative Contribution of the ABC Transporters Cdr1, Pdh1, and Snq2 to Azole Resistance in Candida glabrata

Whaley

Zhang

Caudle

et al. 2018

Antimicrob Agents Chemother

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The utility of the azole antifungals for the treatment of invasive candidiasis is severely hampered by azole resistance in This resistance is mediated almost exclusively by activating mutations in the zinc cluster transcription factor Pdr1, which controls the genes encoding the multidrug resistance transporters Cdr1, Pdh1, and Snq2. However, the specific relative contributions of these transporters to resistance are not known. To address this question, the flipper method was used to delete ,, and in a strain of engineered to carry a clinically relevant activating mutation in Susceptibility testing was performed according to the CLSI guidelines, with minor modifications, and confirmed with Etest strips. Of the single-transporter-deletion strains, only the deletion resulted in a decreased azole MIC. The deletion of in combination with resulted in a moderate decrease in MIC compared to that observed with the deletion of alone. deletion only decreased the MIC in the triple-deletion strain in the absence of both and The deletion of all three transporters in combination decreased the MIC to the level observed in the deletion strains for some, but not all, azoles tested, which indicates that additional Pdr1 targets likely play a minor role in this process. These results indicate that while Cdr1 is the most important Pdr1-mediated multidrug resistance transporter for azole resistance in this clinical isolate, all three of these transporters contribute to its high-level resistance to the azole antifungals.

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“…Several studies recognize specific proteins with the dedicated function to regulate lipid crossing, proving that it is not a matter of simple equilibrium . The artificial liposome model also ignores composition variation in lipid membranes itself; whereas cells invest energy to maintain asymmetry in the two leaflets of the phospholipid bilayer . This observation is not consistent with a purely passive role for the membrane border.…”

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confidence: 99%

Protein‐facilitated transport of hydrophobic molecules across the yeast plasma membrane

2019

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In yeasts, the plasma membrane forms the barrier that protects the cell from the outside world, but also gathers and keeps valuable compounds inside. Although it is often suggested that hydrophobic molecules surpass this checkpoint by simple diffusion, it now becomes evident that protein‐facilitated transport mechanisms allow for selective import and export of triglycerides, fatty acids, alkanes, and sterols in yeasts. During biomass production, hydrophobic carbon sources enter and exit the cell efficiently in a strictly regulated manner that helps avoid toxicity. Furthermore, various molecules, such as yeast pheromones, secondary metabolites and xenobiotics, are exported to ensure cell–cell communication, or increase chances of survival. This review summarizes the current knowledge on how hydrophobic compounds interact with protein‐facilitated transport systems on the plasma membrane and how selective import and export across the yeast plasma membrane is achieved. Both the model organism Saccharomyces cerevisiae, as well as unconventional yeasts are discussed.

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Yeast ABC transporters in lipid trafficking

Cited by 29 publications

References 92 publications

The Paralogous Genes PDR18 and SNQ2, Encoding Multidrug Resistance ABC Transporters, Derive From a Recent Duplication Event, PDR18 Being Specific to the Saccharomyces Genus

The Paralogous Genes PDR18 and SNQ2, Encoding Multidrug Resistance ABC Transporters, Derive From a Recent Duplication Event, PDR18 Being Specific to the Saccharomyces Genus

Relative Contribution of the ABC Transporters Cdr1, Pdh1, and Snq2 to Azole Resistance in Candida glabrata

Protein‐facilitated transport of hydrophobic molecules across the yeast plasma membrane

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