Molecular cloning, structural characterisation and targeted engineering of a novel amphibian antimicrobial peptide from the skin secretion of the tarsier leaf frog, Phyllomedusa Tarsius

Di Wu, Yitian Gao, Xinping Xi, Mei Zhou, Tianbao Chen, Christopher Shaw

Research output: Contribution to conferencePosterpeer-review

Abstract

Antimicrobial peptides (AMPs) in the skin secretions of amphibians, are fundamental components of a unique defence system, which has been developed to protect from microbial invasion. These polypeptides exhibit broad spectrum antimicrobial activity and have attracted attention as potential new antibiotic leads for the treatment of currently resistant bacterial infections. The medusins are a recently discovered AMP family from phyllomedusine leaf frog skin. They exhibit highly-conserved structural characteristics including the N-terminal hexapeptide sequence, LLGMIP-, and a C-terminal tetrapeptide amide sequence, - SKLamide. Here, we report a novel medusin from the skin secretion of the tarsier leaf frog, Phyllomedusa tarsius, which was named, medusin-PT. The mature peptide was identified as encoded by cloned biosynthetic precursor-encoding cDNA, obtained by a RACE technique. Reverse phase HPLC of skin secretion and tandem mass spectrometry, confirmed both the presence and primary structure of medusin-PT (LLGMIPVAITAISALSKLamide). Chemically-synthetic medusin-PT exhibited antimicrobial activity only against the Gram-positive bacterium, S. aureus. However, after the cationicity and amphipathicity of medusin-PT was enhanced by engineering amino acid substitutions, a significant increase in antimicrobial activity against S. aureus as well as the appearance of activity against the Gram-negative bacterium, E. coli and the yeast, C. albicans, was observed. These data provide evidence that medusins may be promising candidates as novel antibiotic leads and that the targeted modification of a natural AMP can provide new insights in antibiotic design and development.
Original languageEnglish
Pages121-121
Number of pages1
Publication statusPublished - Aug 2016
EventDrug Discovery & Therapy World Congress 2016 - Boston, United States
Duration: 22 Aug 201625 Aug 2016

Conference

ConferenceDrug Discovery & Therapy World Congress 2016
CountryUnited States
CityBoston
Period22/08/201625/08/2016

Keywords

  • Amphibian skin secretion, molecular cloning, antimicrobial peptides, medusins

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