Background: Acinetobacter nosocomialis, an opportunistic pathogen responsible for pneumonia and bacteremia, poses a significant threat in intensive care units. The increasing prevalence of colistin-resistant strains in hospital settings has raised serious concerns about patient safety and healthcare outcomes. Therefore, elucidating the mechanisms driving colistin resistance, effectively tracking the spread of resistant strains, and developing strategies to overcome the resistance are imperative.
Methods: We conducted a comparative genomic analysis to uncover the antimicrobial resistance genes or underlying mechanisms by comparing susceptible and resistant bacterial isolates. Additionally, we examined the molecular characteristics of A. nosocomialis strains under colistin-exposed conditions (4 mg/L for 4 hours) using quantitative transcriptomics and proteomics. Label-free proteomics was performed through in-gel digestion, and the eluents were analyzed using LC-MS/MS with Orbitrap Q Exactive Plus.
Results: Through comparative genomic analysis, we discovered a distinct subtype of the capsular polysaccharide (K) locus in A. nosocomialis KAN02, a colistin-resistant strain. This K locus is closely associated with capsular polysaccharide (CPS) production, which contributes to antimicrobial resistance and promotes survival through surface modification. Furthermore, we identified differentially expressed genes (DEGs) and differentially expressed proteins (DEPs). Our comprehensive transcriptomic and proteomic analysis revealed a total of 2,289 DEGs and 660 DEPs. Notably, 14 out of the 22 genes within the K locus showed significant upregulation in both omics datasets, indicating increased synthesis of the capsule in the KAN02 isolate.
Conclusion: This study represents the first comprehensive multi-omics investigation aimed at enhancing our understanding of the mechanisms driving colistin resistance in A. nosocomialis. Through multi-omics analysis, we identified molecular characteristics associated with the mechanisms of colistin resistance in A. nosocomialis KAN02. Our findings revealed that the upregulation of the K locus, as assessed through multi-omics analysis, plays a significant role in conferring colistin resistance in A. nosocomialis KAN02.