Psammaplysin F: A unique inhibitor of bacterial chromosomal partitioning

• Published in: Bioorganic & medicinal chemistry letters Vol. 23; no. 17; pp. 4862 - 4866
• Main Authors: Ramsey, Deborah M., Amirul Islam, Md, Turnbull, Lynne, Davis, Rohan A., Whitchurch, Cynthia B., McAlpine, Shelli R.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-09-2013
• Subjects: Amine; Animals; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antibiotics; Cell division; Chromosomes, Bacterial - metabolism; DNA; DNA, Bacterial - metabolism; Humans; Methicillin-Resistant Staphylococcus aureus - cytology; Methicillin-Resistant Staphylococcus aureus - drug effects; Natural products; Porifera - chemistry; Spiro Compounds - chemistry; Spiro Compounds - pharmacology; Staphylococcal Infections - drug therapy; Staphylococcal Infections - microbiology; Staphylococcus aureus; Tyrosine - analogs & derivatives; Tyrosine - chemistry; Tyrosine - pharmacology; Cell division; Amine; Antibiotics; Natural products; DNA
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2013.06.082

Described is the antibiotic activity of a marine natural product. Psammaplysin F (1) inhibited the growth of four Gram-positive strains by >80% at 50μM, and the amine at position C-20 is responsible for the observed antibacterial activity. When tested against two strains of methicillin resistant Staphylococcus aureus (MRSA), the minimum inhibitory concentrations (MICs) for psammaplysin F (40–80μM) were similar to the structurally-related alkaloid psammaplysin H (2). Psammaplysin F (1) increased membrane permeability by two to four-fold compared to psammaplysin H (2) or control-treated bacteria, respectively. Unlike psammaplysin H (2), we show that psammaplysin F (1) inhibits equal partitioning of DNA into each daughter cell, suggesting that this natural product is a unique prokaryotic cell division inhibitor.