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

LIU, Gaomin, YANG, Fan, LI, Fangfang, LI, Zhongjie, LANG, Yange, SHEN, Bingzheng, WU, Yingliang, LI, Wenxin, HARRISON, Patrick L., STRONG, Peter N., XIE, Yingqiu, MILLER, Keith and CAO, Zhijian (2018). Therapeutic potential of a scorpion venom-derived antimicrobial peptide and its homologs against antibiotic-resistant gram-positive bacteria. Frontiers in Microbiology, 9, p. 1159. [Article]

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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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