Therapeutic potential of a scorpion venom-derived antimicrobial peptide and its homologs against antibiotic-resistant Gram-positive bacteria

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Date

2018-05-28

Authors

Xie, Yingqiu
Liu, Gaomin
Yang, Fan
Li, Fangfang
Li, Zhongjie
Lang, Yange
Shen, Bingzheng
Wu, Yingliang
Li, Wenxin
Harrison, Patrick L.

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Nazarbayev University School of Sciences and Humanities

Abstract

The alarming rise in the prevalence of antibiotic resistance among pathogenic bacteria poses a unique challenge for the development of effective therapeutic agents. Antimicrobial peptides (AMPs) have attracted a great deal of attention as a possible solution to the increasing problem of antibiotic-resistant bacteria. Marcin-18 was identified from the scorpion Mesobuthus martensii at both DNA and protein levels. The genomic sequence revealed that the marcin-18 coding gene contains a phase-I intron with a GT-AG splice junction located in the DNA region encoding the N-terminal part of signal peptide. The peptide marcin-18 was also isolated from scorpion venom. A protein sequence homology search revealed that marcin-18 shares extremely high sequence identity to the AMPs meucin-18 and megicin-18. In vitro, chemically synthetic marcin-18 and its homologs (meucin-18 and megicin-18) showed highly potent inhibitory activity against Gram-positive bacteria, including some clinical antibiotic-resistant strains. Importantly, in a mouse acute peritonitis model, these peptides significantly decreased the bacterial load in ascites and rescued nearly all mice heavily infected with clinical methicillin-resistant Staphylococcus aureus from lethal bacteremia. Peptides exerted antimicrobial activity via a bactericidal mechanism and killed bacteria through membrane disruption. Taken together, marcin-18 and its homologs have potential for development as therapeutic agents for treating antibiotic-resistant, Gram-positive bacterial infections.

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Liu, G., Yang, F., Li, F., Li, Z., Lang, Y., Shen, B., ... Cao, Z. (2018). Therapeutic potential of a scorpion venom-derived antimicrobial peptide and its homologs against antibiotic-resistant Gram-positive bacteria. Frontiers in Microbiology, 9(MAY), [1159]. https://doi.org/10.3389/fmicb.2018.01159

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