A Novel AI-Designed Antimicrobial Peptide Synergistically Potentiates Aminoglycosides against Colistin- and Carbapenem-ResistantAcinetobacter baumannii

Abstract

AbstractThe urgent necessity for new antibiotics becomes glaringly evident with the relentless rise of multidrug-resistant (MDR)Acinetobacter baumanniiin clinical environments, where its infections lead to alarmingly high mortality rates. Antimicrobial peptides (AMPs) represent a promising novel option to combat nosocomial infections caused by MDRA. baumannii. In this study, six novel synthetic peptides were designed through generative artificial intelligence (AI) and synthesized for further experiments. Peptides AIG-R1, AIG-R4, and AIG-R5 showed potent broad-spectrum antibacterial activity against Gram positive and Gram negative pathogens. One of the peptides, AIG-R5, was effective even against colistin and carbapenem-resistant strains ofA. baumannii,prevented biofilm formation, and eradicated established biofilms by 60%. Notably, AIG-R5 enhanced the activity of different antibiotics and was found to exhibit synergistic activity with antibiotics from the Aminoglycoside class. The combination of AIG-R5 and Tobramycin at 1/8×MIC and 1/4×MIC effectively reduced pre-formed biofilms of carbapenem resistantA. baumanniimore than either component alone, as documented by confocal laser scanning microscopy (CLSM). Significant dose reduction and negligible cytotoxicity exhibited by AIG-R5 with aminoglycosides further encourages evaluation of the combination’s therapeutic potentialin vivoagainst MDRA. baumanniiinfections.