Improving the Antimicrobial Performance of Amphiphilic Cationic Antimicrobial Peptides Using Glutamic Acid Full-Scan and Positive Charge Compensation Strategies

Nonselective toxicity of antimicrobial peptides (AMPs)
needs to
be solved urgently for their application. Temporin-PE (T-PE, FLPIVAKLLSGLL-NH2), an AMP extracted from skin secretions of frogs, has high
toxicity and specific antimicrobial activity against Gram-positive
bacteria. To improve the antimicrobial performance of T-PE, a series
of T-PE analogues were designed and synthesized by glutamic acid full-scan,
and then their key positions were replaced with lysine. Finally, E11K4K10, the highest therapeutic indicial
AMP, was screened out. E11K4K10 was
not easy to induce and produce drug-resistant bacteria when used alone,
as well as it could also inhibit the development of the drug resistance
of traditional antibiotics when it was used in combination with the
traditional antibiotics. In addition, E11K4K10 had an excellent therapeutic effect on a mouse model of
pulmonary bacterial infection. Taken together, this study provides
a new approach for the further improvement of new antimicrobial peptides
against the antimicrobial-resistance crisis.