Genômica comparativa e transcriptômica de Acinetobacter baumannii em resposta ao peptídeo LyeTx I mnΔK

Abstract

Acinetobacter baumannii is a major pathogen involved in healthcare-associated infections, characterized by infections in immunosuppressed patients, which can lead to complications such as pneumonia. Treating infections caused by these bacteria is challenging, as the hospital environment favors the selection of microorganisms resistant to commonly used drugs. An alternative is antimicrobial peptides, such as the Toxin I peptide from Lycosa erythrognatha (LyeTx I), which exhibits antimicrobial activity against bacteria and fungi. Its derived form, LyeTx I mnΔK, composed of 16 amino acids, demonstrates synergy with other clinically used antimicrobials, such as meropenem, in in vitro assays for the treatment of A. baumannii infections. Therefore, our objective is to characterize the genome of a new multidrug-resistant A. baumannii strain, AC37, and evaluate the antimicrobial effect of the LyeTx I mnΔK peptide, meropenem, and the combination of the peptide with meropenem through bacterial transcriptome analysis. After genome assembly and annotation using the Unicycler and PGAP programs, 31 genes associated with antibiotic resistance were identified through RGI. Additionally, phylogenetic analyses were conducted with 122 other A. baumannii genomes, identifying three unique genes in the AC37 isolate. Through bacterial mobilome analyses using TNCentral, we identified 13 genes associated with mobile genetic element regions, with two of the three unique genes in AC37, suggesting horizontal transfer events between different species. For transcriptome analyses, gene mapping and counting were performed using Bowtie2 and FeatureCounts, respectively. It was observed that treatment with the peptide resulted in the highest number of differentially expressed genes, followed by the synergy treatment, and lastly, meropenem. We also analyzed the expression of the resistance genes identified in the genome and observed the overexpression of two operons related to bacterial active efflux systems. These systems expel molecules using proton motive force as an energy source. Through functional enrichment analyses, we identified cellular processes such as protein production, export, and secretion, as well as β-lactam resistance activation during treatment with LyeTx I mnΔK, demonstrating the plasticity of the bacterial response to external stressors. This study contributes to the identification of a new A. baumannii isolate and enhances the understanding of bacterial response to a potential new therapeutic target.