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

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

Introduction: 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.

Methods: 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.

Results: 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.

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


Luo, W., Zhang, L., Gao, H., Li, H., Li, X., Wen, Y., Sun, H., Hang, B., Zhang, L., Zhang, W., Liu, X., Wang, R., Wen, B., Shen, J., Zhu, C., Bai, Y., Wang, L., Ding, K., & Hu, J. (2025). AaeAP2a, a scorpion-derived antimicrobial peptide, combats carbapenem-resistant Acinetobacter baumannii via membrane disruption and triggered metabolic collapse. Frontiers in Microbiology, 16, 1673333. https://doi.org/10.3389/fmicb.2025.1673333