Mechanism of action of pseudopteroxazole and pseudopterosin G: Diterpenes from marine origin.

Autor: Janzing NBM; Applied Microbiology, Faculty of Biology and Biotechnology, Ruhr University Bochum, Bochum, Germany., Senges CHR; Applied Microbiology, Faculty of Biology and Biotechnology, Ruhr University Bochum, Bochum, Germany., Dietze P; Applied Microbiology, Faculty of Biology and Biotechnology, Ruhr University Bochum, Bochum, Germany., Haltli B; University of Prince Edward Island, Charlottetown, PE, Canada.; Nautilus Biosciences Croda, Charlottetown, Canada., Marchbank DH; University of Prince Edward Island, Charlottetown, PE, Canada.; Nautilus Biosciences Croda, Charlottetown, Canada., Kerr RG; University of Prince Edward Island, Charlottetown, PE, Canada., Bandow JE; Applied Microbiology, Faculty of Biology and Biotechnology, Ruhr University Bochum, Bochum, Germany.
Jazyk: angličtina
Zdroj: Proteomics [Proteomics] 2024 May; Vol. 24 (10), pp. e2300390. Date of Electronic Publication: 2024 Jan 09.
DOI: 10.1002/pmic.202300390
Abstrakt: Pseudopteroxazole (Ptx) and the pseudopterosins are marine natural products with promising antibacterial potential. While Ptx has attracted interest for its antimycobacterial activity, pseudopterosins are active against several clinically relevant pathogens. Both compound classes exhibit low cytotoxicity and accessibility to targeted synthesis, yet their antibacterial mechanisms remain elusive. In this study, we investigated the modes of action of Ptx and pseudopterosin G (PsG) in Bacillus subtilis employing an unbiased approach that combines gel-based proteomics with a mathematical similarity analysis of response profiles. Proteomic responses to sublethal concentrations of Ptx and PsG were compared to a library of antibiotic stress response profiles revealing that both induce a stress response characteristic for agents targeting the bacterial cell envelope by interfering with membrane-bound steps of cell wall biosynthesis. Microscopy-based assays confirmed that both compounds compromise the integrity of the bacterial cell wall without disrupting the membrane potential. Furthermore, LC-MS E analysis showed that the greater potency of PsG against B. subtilis, reflected in a lower MIC and a more pronounced proteomic response, may be rooted in a more effective association with and penetration of B. subtilis cells. We conclude that Ptx and PsG target the integrity of the gram-positive cell wall.
(© 2024 The Authors. Proteomics published by Wiley‐VCH GmbH.)
Databáze: MEDLINE
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