ISAba1-mediated crp-osmC amplification enhances host-associated fitness in Acinetobacter baumannii

Acinetobacter baumannii is a pathogen, highly adaptable to both hospital- and host-associated environments. Understanding the genetic mechanisms underlying its adaptability is critical for controlling its persistence. Our study identified the crp-osmC gene cluster, flanked by ISAba1 elements, as a significant genetic structure undergoing amplification in A. baumannii. By experimentally mimicking the amplification of this gene cluster, we found that it substantially enhanced bacterial growth and competitive fitness, promoted survival in mouse serum, and improved colonization in murine infection models. Mechanistically, transcriptomic analysis suggested that crp-osmC amplification may enhance host-associated fitness by promoting pathways related to metabolic flexibility and nutrient acquisition, including phenylalanine metabolism, siderophore biosynthesis, and sulfur metabolism. It is noteworthy that this amplification was largely limited to the epidemic ST2 lineage clinical isolates. Intriguingly, gene amplification was also accompanied by reduced biofilm formation and heightened susceptibility to several antibiotics. Overall, ISAba1-mediated amplification of the crp-osmC cluster enhances host-associated fitness in A. baumannii, while the accompanying increase in antibiotic sensitivity reflects a trade-off between survival and resistance.