Critical role of the proton-dependent oligopeptide transporter (POT) in the cellular uptake of the peptidyl nucleoside antibiotic, blasticidin S

Blasticidin S (BlaS) interferes in the cell growth of both eukaryotes and prokaryotes. Its mode of action as a protein synthesis inhibitor has been investigated extensively. However, the mechanism of BlaS transport into the target cells is not understood well. Here, we show that Ptr2, a member of the proton-dependent oligopeptide transporter (POT) family, is responsible for the uptake of BlaS in yeasts Schizosaccharomyces pombe and Saccharomyces cerevisiae. Notably, some mutants of Ptr2 that are dysfunctional in dipeptide uptake were still competent to transport BlaS. Mouse-derived oligopeptide transporter PepT1 conferred BlaS sensitivity in the S. cerevisiae ptr2∆ mutant. Furthermore, Bacterial POT family proteins also potentiated the BlaS sensitivity of E. coli. The role of the POT family oligopeptide transporters in the uptake of BlaS is conserved across species from bacteria to mammals.