*Article* **The Role of Plasma Membrane Pleiotropic Drug Resistance Transporters in the Killer Activity of** *Debaryomyces hansenii* **and** *Wickerhamomyces anomalus* **Toxins**

**Monika Czarnecka 1,\*, Xymena Połomska 1, Cristina Restuccia <sup>2</sup> and Barbara Zarowska ˙ <sup>1</sup>**


**Abstract:** The killer strains of *Debaryomyces hansenii* and *Wickerhamomyces anomalus* species secrete antimicrobial proteins called killer toxins which are active against selected fungal phytopathogens. In our research, we attempted to investigate the role of plasma membrane pleiotropic drug resistance (PDR) transporters (Pdr5p and Snq2p) in the mechanism of defense against killer toxins. *Saccharomyces cerevisiae* mutant strains with strengthened or weakened pleiotropic drug resistance due to increased or reduced number of mentioned PDR efflux pumps were tested for killer toxin susceptibility. The present study demonstrates the influence of the Snq2p efflux pump in immunity to *W. anomalus* BS91 killer toxin. It was also shown that the activity of killer toxins of *D. hansenii* AII4b, KI2a, MI1a and CBS767 strains is regulated by other transporters than those influencing *W. anomalus* killer toxin activity. In turn, this might be related to the functioning of the Pdr5p transporter and a complex cross-talk between several regulatory multidrug resistance networks. To the best of our knowledge, this is the first study that reports the involvement of PDR transporters in the cell membrane of susceptible microorganisms in resistance to killer yeasts' toxins.

**Keywords:** *Debaryomyces hansenii*; *Wickerhamomyces anomalus*; *Saccharomyces cerevisiae*; PDR transporters; killer toxin

**Key Contribution:** This study reveals that PDR transporters in *S. cerevisiae* play a role in resistance to the activity of *D. hansenii* and *W. anomalus* killer toxin, wherein the *pdr1-3 S. cerevisiae* mutant was resistant to *W. anomalus* toxin and the Δ*pdr1*Δ*pdr3 S. cerevisiae* mutant was susceptible to it. Killer toxin activity of *W. anomalus* and *D. hansenii* was affected by Snq2p and Pdr5p transporters, respectively.
