Potential of novel antimicrobial peptide P3 from bovine erythrocytes and its analogs to disrupt bacterial membranes in vitro and display activity against drug-resistant bacteria in a mouse model

Antimicrobial Agents and Chemotherapy
Qinghua ZhangJianhe Hu

Abstract

With the emergence of many antibiotic-resistant strains worldwide, antimicrobial peptides (AMPs) are being evaluated as promising alternatives to conventional antibiotics. P3, a novel hemoglobin peptide derived from bovine erythrocytes, exhibited modest antimicrobial activity in vitro. We evaluated the antimicrobial activities of P3 and an analog, JH-3, both in vitro and in vivo. The MICs of P3 and JH-3 ranged from 3.125 μg/ml to 50 μg/ml when a wide spectrum of bacteria was tested, including multidrug-resistant strains. P3 killed bacteria within 30 min by disrupting the bacterial cytoplasmic membrane and disturbing the intracellular calcium balance. Circular dichroism (CD) spectrometry showed that P3 assumed an α-helical conformation in bacterial lipid membranes, which was indispensable for antimicrobial activity. Importantly, the 50% lethal dose (LD50) of JH-3 was 180 mg/kg of mouse body weight after intraperitoneal (i.p.) injection, and no death was observed at any dose up to 240 mg/kg body weight following subcutaneous (s.c.) injection. Furthermore, JH-3 significantly decreased the bacterial count and rescued infected mice in a model of mouse bacteremia. In conclusion, P3 and an analog exhibited potent antimicrobial activit...Continue Reading

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Citations

Aug 16, 2016·Cellular and Molecular Life Sciences : CMLS·Christopher J Coates, Heinz Decker
Nov 28, 2016·International Journal of Biological Macromolecules·Yuyan ChenRongmin Yu
Nov 23, 2017·Frontiers in Immunology·Patricia PereiroBeatriz Novoa
Apr 25, 2020·Frontiers in Microbiology·Shuli ChouAnshan Shan
Sep 1, 2017·Antonie van Leeuwenhoek·Xiaojing XiaJianhe Hu
May 27, 2021·Probiotics and Antimicrobial Proteins·Haomin WuChangLin Zhou
Nov 1, 2016·ACS Chemical Biology·Charles G StarrWilliam C Wimley

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