Mechanisms of antimicrobial and antiendotoxin activities of a triazine-based amphipathic polymer.

Autor: Kim EY; Department of Biomedical Science, Graduate School, Chosun University, Gwangju, Republic of Korea., Kumar SD; Department of Biomedical Science, Graduate School, Chosun University, Gwangju, Republic of Korea., Bang JK; Division of Magnetic Resonance, Korea Basic Science Institute (KBSI), Ochang, Republic of Korea., Shin SY; Department of Biomedical Science, Graduate School, Chosun University, Gwangju, Republic of Korea.; Department of Cellular & Molecular Medicine, School of Medicine, Chosun University, Gwangju, Republic of Korea.
Jazyk: angličtina
Zdroj: Biotechnology and bioengineering [Biotechnol Bioeng] 2020 Nov; Vol. 117 (11), pp. 3508-3521. Date of Electronic Publication: 2020 Jul 22.
DOI: 10.1002/bit.27499
Abstrakt: TZP4 is a triazine-based amphipathic polymer designed to mimic the amphipathic structure found in antimicrobial peptides. TZP4 showed potent antimicrobial activity comparable to melittin against antibiotic-resistant bacteria, such as methicillin-resistant Staphylococcus aureus and multidrug-resistant Pseudomonas aeruginosa. TZP4 showed high resistance to proteolytic degradation and low tendency to develop drug resistance. The results from membrane depolarization, SYTOX Green uptake, flow cytometry, and gel retardation revealed that the mechanism of antimicrobial action of TZP4 involved an intracellular target rather than the bacterial cell membrane. Furthermore, TZP4 suppressed the messenger RNA levels of inducible nitric oxide synthase and tumor necrosis factor-α (TNF-α) and inhibited the release of nitric oxide and TNF-α in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. BODIPY-TR-cadaverine displacement and dissociation of fluorescein isothiocyanate (FITC)-labeled LPS assays revealed that TZP4 strongly bound to LPS and disaggregated the LPS oligomers. Flow cytometric analysis demonstrated that TZP4 inhibits the binding of FITC-conjugated LPS to RAW264.7 cells. These observations indicate that TZP4 may exert its antiendotoxic activity by directly binding with LPS and inhibiting the interaction between LPS and CD14 + cells. Collectively, TZP4 is a promising drug candidate for the treatment of endotoxic shock and sepsis caused by Gram-negative bacterial infections.
(© 2020 Wiley Periodicals LLC.)
Databáze: MEDLINE
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