| Full text | |
| Author(s): |
Boaro, Andreia
;
Ageitos, Lucia
;
Torres, Marcelo Der Torossian
;
Blasco, Esther Broset
;
Oztekin, Sebahat
;
de la Fuente-Nunez, Cesar
Total Authors: 6
|
| Document type: | Journal article |
| Source: | CELL REPORTS PHYSICAL SCIENCE; v. 4, n. 7, p. 22-pg., 2023-07-19. |
| Abstract | |
Antimicrobial peptides (AMPs) derived from natural toxins and venoms offer a promising alternative source of antibiotics. Here, through structure-function-guided design, we convert two natural AMPs derived from the venom of the solitary eumenine wasp Eu-menes micado into a-helical AMPs with reduced toxicity that kill Gram-negative bacteria in vitro and in a preclinical mouse model. To identify the sequence determinants conferring antimicrobial ac-tivity, an alanine scan screen and strategic single lysine substitutions are made to the amino acid sequence of these natural peptides. These efforts yield a total of 34 synthetic derivatives, including alanine substituted and lysine-substituted sequences with stabilized a-helical structures and increased net positive charge. The resulting lead synthetic peptides kill the Gram-negative pathogens Escheri-chia coli and Pseudomonas aeruginosa (PAO1 and PA14) by rapidly permeabilizing both their outer and cytoplasmic membranes, exhibit anti-infective efficacy in a mouse model by reducing bacte-rial loads by up to three orders of magnitude, and do not readily select for bacterial resistance. (AU) | |
| FAPESP's process: | 16/10585-4 - Mechanistic aspects regarding the induced decomposition of hydroperoxides and silylperoxides derived from lophine |
| Grantee: | Andréia Boaro |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| FAPESP's process: | 19/15871-3 - Light emitting arginine derivatives as tags for antimicrobial peptides |
| Grantee: | Andréia Boaro |
| Support Opportunities: | Scholarships abroad - Research Internship - Doctorate |