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CCeMMP Seminar Series – A/Prof. Natalie Zeytuni July 2022

Structural insights into the cytotoxic peptides ATP-driven exporter and drug resistance

Staphylococcus aureus is a major human pathogen that has acquired an alarming broad-spectrum resistance to many of the commonly used antibiotics including beta-lactams such as penicillin. S. au\reus often causes hospital- and community- associated infections responsible for significant morbidity and death. Staphylococci infections are mediated trough a large array of secreted toxins including the phenol-soluble modulins (PSMs). PSMs are amphipathic, α-helical peptides with pronounced surfactant-like properties that have multiple key roles in pathogenesis. A specialized ATP-binding cassette (ABC) transport system exports PSMs to the extracellular environment and is essential for bacterial growth by providing an immunity against self-expressed PSMs. Here, we present the structural characterization of the PSM transporter determined by high-resolution single-particle cryo-EM and X-ray crystallography accompanied with functional characterization in vivo.

Dr. Natalie Zeytuni

Department of Anatomy and Cell Biology

McGill University