Pleiotropic Drug Resistance Mechanisms in Saccharomyces Cerevisiae

Pleiotropic drug resistance (PDR) in S. cerevisiae arises from the coordinated action of multiple efflux pumps, regulatory factors and signalling pathways that collectively reduce cellular susceptibility to diverse xenobiotics. Central to this phenomenon are ATP-binding cassette (ABC) transporters such as Pdr5p and Snq2p, which actively expel compounds across the plasma membrane. The expression of these transporters is controlled by zinc-cluster transcription factors Pdr1p and Pdr3p, which recognise pleiotropic drug response elements (PDREs) in target promoters. Beyond direct transcriptional control, mitochondrial status and retrograde signalling contribute additional layers of regulation, linking energy metabolism and organellar dysfunction to drug resistance. Chromatin structure and histone modification further modulate the inducible nature of the PDR network. Collectively, these mechanisms not only underpin yeast survival under chemical stress but also serve as a model for understanding multidrug resistance in pathogenic fungi and tumour cells. Practical applications extend from improving antifungal strategies to optimising biotechnological fermentation processes in industries that face inhibitory compounds.

Research from Nature Portfolio

Recent studies have elucidated the collaborative roles of the histone chaperone Rtt106 and the SWI/SNF chromatin-remodelling complex in activating PDR network genes. In S. cerevisiae, Rtt106 preferentially localises to promoters of key PDR genes under basal conditions through interaction with Pdr3p, while SWI/SNF is essential for both basal and drug-induced transcriptional responses. Loss of either Rtt106 or SWI/SNF components sensitises both laboratory and drug-resistant clinical isolates to antifungal agents, highlighting these factors as promising targets for adjunct therapies that restore drug susceptibility.

Pleiotropic Drug Resistance Mechanisms in Saccharomyces Cerevisiae publication trend

The graph below shows the total number of articles in pleiotropic drug resistance mechanisms in saccharomyces cerevisiae across all publications each year (not limited to Nature Index journals).

Technical terms

Pleiotropic drug resistance (PDR) network: A coordinated system of efflux transporters, regulators and signalling pathways that expel diverse toxic compounds from the cell.

ATP-binding cassette (ABC) transporter: A membrane protein that utilises ATP hydrolysis to transport substrates, including drugs, across cellular membranes.

Retrograde signalling: Communication from mitochondria to the nucleus that adjusts gene expression in response to organellar function.

Chromatin remodeller SWI/SNF: A multiprotein complex that repositions nucleosomes to permit or restrict access of transcription factors to DNA.

Histone chaperone Rtt106: A protein that facilitates histone assembly and recruitment to gene promoters, modulating transcriptional responses.

References

1. Fungal Drug Response and Antimicrobial Resistance. Journal of Fungi (2023).
2. SWI/SNF and the histone chaperone Rtt106 drive expression of the Pleiotropic Drug Resistance network genes. Nature Communications (2022).
3. RPD3 and UME6 are involved in the activation of PDR5 transcription and pleiotropic drug resistance in ρ0 cells of Saccharomyces cerevisiae. BMC Microbiology (2021).