Adaptive survival strategies of Acinetobacter baumannii under different classes of antibiotic stress revealed through transcriptomic profiling.

Acinetobacter baumannii is an opportunistic Gram-negative pathogen known for its multidrug-resistant and extensively drug-resistant strains, posing a significant global health threat. Its ability to rapidly adapt to diverse environments, including antibiotic pressure, is underpinned by metabolic and physiological plasticity, which contributes both to resistance and virulence. However, the molecular strategies by which A. baumannii modulates metabolic pathways and virulence determinants to survive antibiotic treatment remain incompletely understood. This study aims to understand the global transcriptional responses and adaptive strategies employed by Acinetobacter baumannii under antibiotic stress, with a focus on identifying metabolic, regulatory, and effector pathways that underlie persistence and resistance mechanisms. We analysed publicly available transcriptomic datasets of A. baumannii exposed to five classes of antibiotics to identify differentially expressed genes and associated pathways. Functional and pathway analyses were then used to classify bacterial survival strategies under each antibiotic. Overall, metabolic pathways play a predominant role across all five antibiotic classes, exerting a greater influence than physiological factors. Among physiological factors, ABC transporters, the AdeABC efflux pump, and autoinducer synthases emerge as major contributors to bacterial survival, collectively enhancing adaptive resistance and persistence under antibiotic stress. Our comparative transcriptomic analysis shows that A. baumannii predominantly exhibits a metabolically active defensive strategy in response to bactericidal agents, while the bacteriostatic antibiotic tigecycline induces a pessimistic, energy-conserving state.