Daptomycin, a last-resort antibiotic, binds ribosomal protein S19 in humans.

ABSTRACT:

Background

Daptomycin is a recently introduced, last-resort antibiotic that displays a unique mode of action against Gram-positive bacteria that is not fully understood. Several bacterial targets have been proposed but no human binding partner is known.

Methods

In the present study we tested daptomycin in cell viability and proliferation assays against six human cell lines, describe the synthesis of biotinylated and fluorescently labeled analogues of daptomycin. Biotinylated daptomycin was used as bait to isolate the human binding partner by the application of reverse chemical proteomics using T7 phage display of five human tumor cDNA libraries. The interaction between the rescued protein and daptomycin was validated via siRNA knockdown, DARTS assay and immunocytochemistry.<

SUBMITTER: Gotsbacher MP 

PROVIDER: S-EPMC5494143 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature