Acinetobacter baumannii, a leading cause of hospital-acquired infections, is notorious for its multidrug resistance and ability to persist in clinical settings. New research led by Yuqin Song and Jie Feng from the Institute of Microbiology, Chinese Academy of Sciences, has uncovered a genetic mechanism that helps the pathogen adapt to its host—and it comes with a surprising cost. The study, published in mLife, identifies insertion sequence (IS)-mediated amplification of the crp-osmC gene cluster as a previously unrecognized driver of host-associated fitness.
The researchers analyzed 582 complete A. baumannii genomes and found that the insertion sequence ISAba1 was most frequently associated with gene amplification. Beyond known antimicrobial resistance genes, they discovered a recurrently amplified crp-osmC gene cluster flanked by ISAba1 elements, which they designated the composite transposon Tn7691. A broader analysis of 7,490 genomes showed a strong association between Tn7691 and crp-osmC amplification with the globally prevalent high-risk ST2 lineage and its single-locus variants. This link to a successful clinical lineage underscores the potential clinical relevance of the finding.
To test the biological impact, the team experimentally increased the copy number of the crp-osmC cluster in A. baumannii. The amplified strain displayed improved growth at later stages and a clear competitive advantage in vitro. More importantly, it enhanced bacterial fitness in mouse models of pulmonary infection and intestinal colonization, and showed substantially improved survival and competitive fitness in mouse serum. These results support a role for crp-osmC amplification in host-associated adaptation.
Transcriptomic analysis revealed that crp-osmC amplification was associated with increased expression of genes involved in phenylalanine metabolism, siderophore biosynthesis, and sulfur metabolism—changes that may improve metabolic flexibility and nutrient acquisition under nutrient-limited host conditions. The researchers further demonstrated that CRP retained its DNA-binding activity and directly bound 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 exhibited reduced expression of genes involved in pili and biofilm formation, along with decreased biofilm formation. Unexpectedly, crp-osmC amplification also increased susceptibility to multiple antibiotics. These findings suggest that enhanced host-associated fitness may be accompanied by a trade-off in antibiotic resistance, a critical implication for understanding the clinical success of A. baumannii. The study expands the conventional view that IS-mediated gene amplification primarily drives antimicrobial resistance, showing that ISAba1-mediated amplification can also reshape host-associated fitness. This work provides new insights into the genomic plasticity and adaptive evolution of A. baumannii and may inform future strategies to combat infections.
