# AaeAP2a, a scorpion-derived antimicrobial peptide, combats carbapenem-resistant Acinetobacter baumannii via membrane disruption and triggered metabolic collapse

## TL;DR

A scorpion-derived peptide called AaeAP2a effectively fights antibiotic-resistant bacteria by damaging their membranes and disrupting metabolism.

## Contribution

AaeAP2a is a novel scorpion-derived antimicrobial peptide that combats CRAB through membrane disruption and metabolic collapse.

## Key findings

- AaeAP2a shows potent antibacterial activity against CRAB and inhibits biofilm formation.
- The peptide disrupts bacterial membranes and reduces ATP production while inducing reactive oxygen species.
- In a mouse sepsis model, AaeAP2a improved survival and reduced bacterial burden in organs.

## Abstract

Carbapenem-resistant Acinetobacter baumannii (CRAB) poses a significant global health challenge owing to its high mortality rates and widespread antibiotic resistance. While the clinical utility of last-resort antibiotics, such as colistin, remains limited. Consequently, developing novel antimicrobial agents is imperative. Antimicrobial peptides have emerged as promising candidates against multidrug-resistant pathogens. Animal venom constitutes a rich reservoir of bioactive peptides.

In this study, in vitro experiments were conducted to assess the antibacterial activity of the scorpion-derived peptide AaeAP2a against CRAB, its inhibition of biofilm formation, as well as its stability and biocompatibility. Additionally, the antibacterial mechanism was investigated, and in vivo efficacy was evaluated using a mouse model of peritonitis-associated sepsis.

AaeAP2a exhibits potent antibacterial activity against CRAB and a significant inhibitory effect on biofilm formation. Moreover, AaeAP2a maintains high stability under a broad range of stressful physicochemical conditions and exhibits promising biocompatibility in vitro. Mechanistically, AaeAP2a disrupts bacterial membrane integrity, increases membrane permeability, reduces the NAD+/NADH ratio, dissipates the proton motive force, decreases ATP production, and induces reactive oxygen species and hydroxyl radical accumulation. Moreover, in a mouse model of peritonitis-associated sepsis, AaeAP2a treatment enhanced survival rates and reduced bacterial burdens in key organs.

These findings underscore the potential of AaeAP2a as a promising therapeutic agent for CRAB infections, offering novel strategies for addressing antimicrobial resistance.