A new study has revealed a previously unrecognized mechanism by which Acinetobacter baumannii, a major hospital-associated pathogen, adapts to its host. The research, led by Yuqin Song and Jie Feng from the Institute of Microbiology, Chinese Academy of Sciences, shows that amplification of the crp-osmC gene cluster, mediated by the insertion sequence ISAba1, enhances bacterial fitness during infection but simultaneously reduces antibiotic resistance and biofilm formation.
A. baumannii is known for its multidrug resistance and persistence in clinical environments, making it a significant threat to hospitalized patients. The study analyzed 582 complete genomes and found that ISAba1 was the insertion sequence most frequently associated with gene amplification. Beyond known resistance genes, the researchers identified a recurrently amplified crp-osmC cluster flanked by ISAba1 elements, forming a composite transposon designated Tn7691. Analysis of 7,490 genomes showed a strong association between Tn7691 and the globally prevalent high-risk ST2 lineage.
To test the biological significance, the team experimentally increased the copy number of the crp-osmC cluster. The amplified strain exhibited improved growth and a competitive advantage in co-culture, and more importantly, enhanced fitness in mouse models of pulmonary infection and intestinal colonization. It also showed better survival in mouse serum, supporting a role in host adaptation. Transcriptomic analysis linked these benefits to increased expression of genes involved in phenylalanine metabolism, siderophore biosynthesis, and sulfur metabolism, suggesting improved metabolic flexibility and nutrient acquisition. The researchers further demonstrated that CRP directly binds the promoter of the siderophore-associated bas gene cluster, supporting its regulatory role in iron acquisition.
However, the adaptive advantage came with apparent costs. The amplified strain showed reduced expression of genes involved in pili and biofilm formation, and decreased biofilm formation. Unexpectedly, it also increased susceptibility to multiple antibiotics. These findings suggest a trade-off between host-associated fitness and antibiotic resistance.
The study, published in mLife, expands the conventional view that insertion sequence-mediated gene amplification primarily drives antimicrobial resistance. It demonstrates that ISAba1-mediated amplification can reshape host-associated fitness, providing new insights into the genomic plasticity and clinical success of A. baumannii. The work was supported by the National Key Research and Development Program of China and the National Natural Science Foundation of China.
