Multimerization of a Proline-Rich Antimicrobial Peptide, Chex-Arg20, Alters Its Mechanism of Interaction with the Escherichia coli Membrane

作者：Li Wenyi; O'Brien Simpson Neil M; Tailhades Julien; Pantarat Namfon; Dawson Raymond M; Otvos Laszlo Jr; Reynolds Eric C; Separovic Frances; Hossain Mohammed Akhter; Wade John D^*

来源：Chemistry & Biology, 2015, 22(9): 1250-1258.

DOI：10.1016/j.chembiol.2015.08.011

A3-APO, a de novo designed branched dimeric pro-line-rich antimicrobial peptide (PrAMP), is highly effective against a variety of in vivo bacterial infections. We undertook a selective examination of the mechanism for the Gram-negative Escherichia coli bacterial membrane interaction of the monomer (Chex-Arg20), dimer (A3-APO), and tetramer (A3-APO disulfide-linked dimer). All three synthetic peptides were effective at killing E. coli. However, the tetramer was 30-fold more membrane disruptive than the dimer while the monomer showed no membrane activity. Using flow cytometry and high-resolution fluorescent microscopy, it was observed that dimerization and tetramerization of the Chex-Arg20 monomer led to an alteration in the mechanism of action from non-lytic/membrane hyperpolarization to membrane disruption/depolarization. Our findings show that the membrane interaction and permeability of Chex-Arg20 was altered by multimerization.

• 出版日期2015-9-17
• 单位河北医科大学