Genomic and Phenotypic Characterization of a Drug-Susceptible Acinetobacter baumannii Reveals Increased...

Acinetobacter baumannii is an opportunistic pathogen notable for multidrug resistance and environmental persistence. We characterized a clinical isolate, HKAB-1, which exhibits pronounced virulence-associated traits despite being highly susceptible to all tested antibiotics. HKAB-1 exhibited superior growth in MH2B, serum and desiccating conditions, robust biofilm formation, and active motility. Whole-genome sequencing identified two heme utilization clusters, multiple siderophore biosynthesis pathways, and other virulence-associated genes. Gene expression analysis revealed significant upregulation of heme utilization and siderophore biosynthetic gene clusters under serum exposure, indicating activation of iron uptake pathways under host-like conditions. Biofilm-associated genes, including bap, PNAG biosynthetic genes, and type IV pili components, were notably upregulated in biofilm-forming cells, supporting their role in driving the enhanced biofilm phenotype. Conversely, adeB, encoding a major RND efflux pump, was markedly downregulated, potentially explaining its drug-susceptible phenotype. Comparative genomic analysis highlighted differences in genes related to nutrient transport, metabolic pathways, and membrane biogenesis that may underpin its enhanced growth. These findings point to a potential trade-off between antibiotic resistance and virulence, underscoring the importance of monitoring antibiotic-susceptible yet highly virulent A. baumannii isolates as potential reservoirs for resistance evolution. Further investigation is warranted to elucidate the mechanisms underlying this phenotypic balance.