Toward a Drosophila melanogaster Model of Acinetobacter baumannii Infection

Acinetobacter baumannii, a multidrug-resistant member of the ESKAPE pathogen group, poses a major global public health threat due to its persistence in clinical environments, rapid acquisition of antibiotic resistance, and limited treatment options. Although mammalian and non-mammalian infection models have advanced our understanding of A. baumannii pathogenesis, many are constrained by cost, scalability, or experimental tractability. While Drosophila melanogaster S2 cell lines have proven valuable for investigating A. baumannii–host interactions, development of a whole-organism D. melanogaster infection model has remained limited. To our knowledge, the only previous in vivo study reports no significant infection-associated mortality relative to controls. Here, we demonstrate that A. baumannii can cause lethal infection in adult D. melanogaster. Across a series of experiments, inoculation with two A. baumannii strains, A118 and AMA_NO, produced significantly increased mortality relative to PBS-inoculated controls. Moreover, the magnitude of mortality differed between bacterial strains under some experimental conditions, with the multidrug-resistant clinical isolate AMA_NO producing greater mortality than A118, consistent with strain-specific differences in pathogenic potential. Infection outcomes depended on the experimental context, indicating that further refinement will be important for improving the reproducibility and sensitivity of the system. Together, these findings establish that D. melanogaster can support lethal A. baumannii infection and detect biologically meaningful differences among bacterial strains, providing a foundation for its continued development as an accessible and genetically tractable whole-organism model for investigating A. baumannii virulence and host–pathogen interactions.