Comparative Genomics and Transcriptomics of Acinetobacter baumannii in Response to LyeTx I mndeltaK Peptide

Acinetobacter baumannii is a critical pathogen in healthcare-associated infections, particularly affecting immunocompromised patients and causing complications like pneumonia. Treatment is challenging due to the selection of multidrug-resistant strains. Antimicrobial peptides, such as LyeTx I mndeltaK, represent a promising alternative, exhibiting broad-spectrum activity and synergy with antibiotics like meropenem. This study aimed to characterize the genome of a novel multidrug-resistant A. baumannii AC37 isolate and evaluate the antimicrobial effects of LyeTx I mndeltaK, and a combination with meropenem through transcriptomic analysis. Genome assembly and annotation revealed 31 antibiotic resistance genes, and phylogenetic analysis with 123 A. baumannii genomes identified 3 unique genes in AC37. Mobilome analysis indicated 13 genes associated with mobile genetic elements, including 2 of the unique genes, emphasizing events of horizontal gene transfer. Transcriptomic analysis showed the LyeTx I mndeltaK treatment induced the most differentially expressed genes. Upregulation of two efflux pump operons was observed upon peptide treatment and these systems play the role of ejecting molecules by utilizing the proton motive force as an energy source. Functional enrichment analysis revealed activation of pathways for protein production, export, and secretion upon treatment with LyeTx I mndeltaK, and downregulation of oxidative phosphorylation genes in the synergistic treatment, highlighting the plasticity of the bacterial response to external stresses. This study contributes to the characterization of a new A. baumannii isolate and provides insights into the bacterial response to a potential novel therapeutic strategy.