• Port-a-Patch

    世界最小パッチクランプセットアップ
  • Port-a-Patch

    誰でもデータ取得 - 教育ツールとして最適
  • Port-a-Patch

    細胞, オルガネラ, 脂質二分子膜
  • Port-a-Patch

    世界で最も歴史あるプレーナー式パッチクランプ装置
  • Port-a-Patch

    細胞内灌流実験に最適

2020 - A pleurocidin analogue with greater conformational flexibility, enhanced antimicrobial potency and in vivo therapeutic efficacy

 icon vpp  Vesicle Prep Pro and icon pap Port-a-Patch publication in Communications Biology (2020)

Authors:
Manzo G., Hind C.K., Ferguson P.M., Amison R.T., Hodgson-Casson A.C., Ciazynska K.A., Weller B.J., Clarke M., Lam C., Man R.C.H., O'Shaughnessy B.G., Clifford M., Bui T.T., Drake A.F., Atkinson R.A., Lam J.K.W., Pitchford S.C., Page C.P., Phoenix D.A., Lorenz C.D., Sutton J.M., Mason A.J.

Journal:

Communications Biology (2020) doi: 10.1038/s42003-020-01420-3


Abstract: 

Antimicrobial peptides (AMPs) are a potential alternative to classical antibiotics that are yet to achieve a therapeutic breakthrough for treatment of systemic infections. The antibacterial potency of pleurocidin, an AMP from Winter Flounder, is linked to its ability to cross bacterial plasma membranes and seek intracellular targets while also causing membrane damage. Here we describe modification strategies that generate pleurocidin analogues with substantially improved, broad spectrum, antibacterial properties, which are effective in murine models of bacterial lung infection. Increasing peptide–lipid intermolecular hydrogen bonding capabilities enhances conformational flexibility, associated with membrane translocation, but also membrane damage and potency, most notably against Gram-positive bacteria. This negates their ability to metabolically adapt to the AMP threat. An analogue comprising D-amino acids was well tolerated at an intravenous dose of 15 mg/kg and similarly effective as vancomycin in reducing EMRSA-15 lung CFU. This highlights the therapeutic potential of systemically delivered, bactericidal AMPs.


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