Acinetobacter baumannii, a major nosocomial pathogen known for its multidrug resistance and persistence in clinical settings, may owe part of its success to a previously unrecognized genetic mechanism that boosts its ability to colonize and survive within a host, according to a new study published in mLife. The research, led by Yuqin Song and Jie Feng from the Institute of Microbiology, Chinese Academy of Sciences, identifies insertion sequence-mediated gene amplification as a driver of host-associated fitness, expanding the conventional view that such amplifications primarily serve to confer antimicrobial resistance.
The team analyzed 582 complete A. baumannii genomes and found that the insertion sequence ISAba1 was most frequently associated with gene amplification. Beyond well-known resistance genes, they discovered a recurrently amplified crp-osmC gene cluster flanked by ISAba1 elements, a structure they designated the composite transposon Tn7691. Screening 7,490 genomes revealed a strong association between Tn7691 and crp-osmC amplification with the globally prevalent high-risk ST2 lineage and its single-locus variants, linking the genetic structure to strains that are already successful in clinical environments.
To test the biological significance, the researchers experimentally increased the copy number of the crp-osmC cluster in A. baumannii. The amplified strain showed improved growth at later stages and a competitive advantage in vitro. More importantly, it enhanced bacterial fitness in mouse pulmonary infection and intestinal colonization models, and improved survival and competitive fitness in mouse serum, supporting a role in host adaptation. Transcriptomic analysis linked the amplification to increased expression of genes involved in phenylalanine metabolism, siderophore biosynthesis, and sulfur metabolism, potentially improving metabolic flexibility and nutrient acquisition under host conditions. The researchers further showed that CRP retained DNA-binding activity and directly bound the promoter of the siderophore-associated bas gene cluster, supporting a 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, decreased biofilm formation, and unexpectedly increased susceptibility to multiple antibiotics. These findings suggest a trade-off between host-associated fitness and antibiotic resistance in A. baumannii.
The study, published in the open-access journal mLife, provides new insights into the genomic plasticity and adaptive evolution of this pathogen. For clinicians, the results imply that strains with crp-osmC amplification may be more adept at colonizing patients but could be more treatable with certain antibiotics, potentially informing treatment strategies. For researchers, the work highlights the need to look beyond resistance when studying insertion sequence-mediated amplification. The findings underscore how genetic elements like ISAba1 can reshape bacterial physiology in ways that affect both virulence and drug susceptibility, with implications for managing one of the most troublesome hospital-acquired infections worldwide.
