Antibacterial efficacy and mechanism of the novel antimicrobial peptide lachnospirin-1 against <i>Acinetobacter baumannii</i>

The treatment of carbapenem-resistant <i>A. baumannii</i> (CRAB) infections has become a major global medical challenge; therefore, there is an urgent need for new antimicrobial development. Antimicrobial peptides hold great promising potential due to their rapid bactericidal activity and low induction of drug resistance. In this study, we screened and synthesized the antimicrobial peptide lachnospirin-1, which exhibited significant bactericidal activity against CRAB and can also effectively eliminate its biofilms and persister cells. Mechanism studies, including fluorescent probe detection, transmission electron microscopy observations, and molecular dynamics simulations, et al. indicated that lachnospirin-1 exerts its effects through multiple mechanisms, such as disrupting bacterial cell membranes, neutralizing lipopolysaccharide, as well as inducing oxidative stress, which also demonstrates its certain potential. In addition, the favorable safety profile and effective <i>in vivo</i> bactericidal activity of lachnospirin-1 were determined by mouse models. Overall, our study found that lachnospirin-1 has considerable research potential as a lead compound and possesses latent value as a clinical therapy for refractory infections caused by CRAB.