The Trp-rich Antimicrobial Amphiphiles With Intramolecular Aromatic Interactions for the Treatment of Bacterial Infection

• DOI: 10.3389/fmicb.2021.733441
• Publication Date: 2021-10-13T18:27:30Z
• Authors: Zhihua Wang; Qiuke Li; Jinze Li; Jiawei Li; Lu Shang; Shuli Chou; Yinfeng Lyu; Anshan Shan
• Keywords: Economic shortage

Antibiotic resistance is emerging as a hot issue with the abuse and overuse of antibiotics, shortage effective antimicrobial agents against multidrug resistant bacteria creates huge problem to treat threatening nosocomial skin soft tissue infection. Antimicrobial peptides (AMPs) exhibite enormous potential one most promising candidates antibiotic fight pathogenic infections because its unique membrane penetration mechanism kill pathogens, whereas clinical application AMPs still faces challenges production cost, stability, safety, design strategy. Herein, series Trp-rich was designed following principle paired Trp plated at ith ith+4 position on backbone peptides, based template (VKKX)4, where X represents W, A, or L, study effect intramolecular aromatic interactions bioactivity AMPs. Through comparing performance, hemolysis, cytotoxicity, VW5 which equipped characters direct efficacy (GM=1.68μM) physical destruction bacterial (SEM electron microscopy) stood out from engineering peptides. also performed well in mice models, could significantly decrease colony (VW5 vs infection group, 12.72±2.26 5.52±2.01×109CFU/abscess), area dermo-necrosis 0.74±0.29 1.86±0.98mm2) inflammation cytokine levels abscess site without causing toxicity skin. Overall, this provides strategy diminish randomness exploration novel