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Mechanisms of bactericidal action and resistance of polymyxins for Gram-positive bacteria

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Abstract

Polymyxins are cationic antimicrobial peptides used as the last-line therapy to treat multidrug-resistant Gram-negative bacterial infections. The bactericidal activity of polymyxins against Gram-negative bacteria relies on the electrostatic interaction between the positively charged polymyxins and the negatively charged lipid A of lipopolysaccharide (LPS). Given that Gram-positive bacteria lack an LPS-containing outer membrane, it is generally acknowledged that polymyxins are less active against Gram-positive bacteria. However, Gram-positive bacteria produce negatively charged teichoic acids, which may act as the target of polymyxins. More and more studies suggest that polymyxins have potential as a treatment for Gram-positive bacterial infection. This mini-review discusses recent advances in the mechanism of the antibacterial activity and resistance of polymyxins in Gram-positive bacteria.

Key Points

• Teichoic acids play a key role in the action of polymyxins on Gram-positive bacteria.

• Polymyxin kills Gram-positive bacteria by disrupting cell surface and oxidative damage.

• Modification of teichoic acids and phospholipids contributes to polymyxin resistance in Gram-positive bacteria.

• Polymyxins have potential as a treatment for Gram-positive bacterial infection.

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Author contribution statement

YJ and YZ conceived and designed the review. CD, FJ, and LY collected the data. YJ, MQ, LQ, and YZ wrote the manuscript. All authors read and approved the manuscript.

Funding

This research was supported by the grants from Zhejiang Provincial Natural Science Foundation of China (LY20C010003), National Natural Science Foundation of China (31670114), and the National Key R&D Program of China (2017YFC1600100).

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  1. College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, 310014, China

    Jianhua Yin, Qiu Meng, Dan Cheng, Jianv Fu, Yanqiu Liu & Zhiliang Yu

  2. State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China

    Qixia Luo

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Yin, J., Meng, Q., Cheng, D. et al. Mechanisms of bactericidal action and resistance of polymyxins for Gram-positive bacteria. Appl Microbiol Biotechnol 104, 3771–3780 (2020). https://doi.org/10.1007/s00253-020-10525-y

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