Scorpion Venom-Derived Peptides: A New Weapon Against Carbapenem-Resistant Acinetobacter baumannii

TL;DR

Scorpion venom peptides show strong antibacterial and antibiofilm effects against drug-resistant Acinetobacter baumannii, suggesting potential as new treatments.

Contribution

Discovery of two scorpion venom peptides with dual bactericidal and antibiofilm mechanisms against carbapenem-resistant A. baumannii.

Findings

Pantinin-1 and pantinin-2 exhibit bactericidal activity with MICs of 6.25 μM and 12.5 μM.

Peptides damage bacterial membranes and inhibit biofilm formation and key gene expression.

Low cytotoxicity and efficacy at low concentrations highlight therapeutic potential.

Abstract

Acinetobacter baumannii (A. baumannii) is an opportunistic pathogen associated with healthcare-related infections and is of particular concern due to its high level of antibiotic resistance and its ability to form biofilms. The global emergence of carbapenem-resistant A. baumannii highlights the urgent need for alternative therapeutic strategies. This study investigated the antibacterial and antibiofilm activities of two scorpion venom-derived peptides, pantinin-1 and pantinin-2, against a reference strain and a clinical isolate of A. baumannii. We found that both peptides, in the non-cytotoxic concentration range, have strong bactericidal activity, showing a minimum inhibitory concentration (MIC) of 6.25 μM and 12.5 μM for pantinin 1 and 2, respectively. Scanning electron microscopy (SEM) analysis showed that the peptides cause extensive damage to the bacterial membrane. Furthermore, both peptides showed potent antibiofilm activity, inhibiting adhesion and maturation, arresting biofilm expansion, and reducing the expression of key biofilm-associated genes (bap, pgaA, and smpA). Altogether, these findings indicate that pantinin-1 and pantinin-2 act through a dual mechanism, combining bactericidal and antivirulence activities. Their strong efficacy at low micromolar concentrations, together with low cytotoxicity, underscores their potential as innovative therapeutic candidates against infections caused by carbapenem-resistant, biofilm-forming A. baumannii.

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