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1.D.23 The Phenylene Ethynylene Pore-forming Antimicrobial (PEPA) Family

Phenylene ethynylenes comprise a prototypical class of syntheic antimicrobial compounds that mimic antimicrobial peptides produced by eukaryotes and have broad-spectrum antimicrobial activity. Yang et al. (2008) showed that bacterial membrane permeation by these antimicrobials is cooperative and depends on the presence of negative intrinsic curvature lipids, such as phosphatidylethanolamine (PE). A PE-knockout mutant strain of Escherichia coli out-survives the wild type against membrane-active phenylene ethynylene antimicrobials, whereas the opposite is true when challenged with traditional metabolic antibiotics. PE alows efficient generation of the negative curvature required for circumferential barrel formation yielding of an induced membrane pore.

The reaction catalyzed by phenylene ethynylene is:

ions (in) ions (out)

References associated with 1.D.23 family:

Yang, L., V.D. Gordon, D.R. Trinkle, N.W. Schmidt, M.A. Davis, C. DeVries, A. Som, J.E. Cronan, Jr, G.N. Tew, and G.C. Wong. (2008). Mechanism of a prototypical synthetic membrane-active antimicrobial: Efficient hole-punching via interaction with negative intrinsic curvature lipids. Proc. Natl. Acad. Sci. USA 105: 20595-20600. 19106303