Transcriptomic Insights into the Virulence of Acinetobacter baumannii During Infection: Role of Iron Uptake and Siderophore Production Genes

Abstract

Acinetobacter baumannii is a top-priority pathogen as classified by the World Health Organisation. It causes life-threatening infections in immunocompromised patients, resulting in prolonged hospitalisation and high mortality. Increasing cases of community-acquired A. baumannii infections with rapid progression and severe infections have been reported. This study used the previously described Galleria mellonella infection model to investigate the virulence mechanisms of the community strain C98 (Ab-C98) via transcriptomic analysis using direct RNA sequencing. This strain showed greater killing and more rapid colonisation in the larvae than a clinical reference strain (ATCC BAA1605). Differential gene expression analysis revealed the significant upregulation of three major iron clusters: the acinetobactin and baumannoferrin clusters for siderophore production and the Feo system for ferrous iron uptake. Targeted knockout of siderophore production genes (basC, bfnD and isochorismatase family protein) significantly attenuated virulence in mutants with minimal impact on the bacterial growth in vivo. Overall, this study highlights the virulence of basC, isochorismatase family protein and bfnD in the pathogenicity of A. baumannii. As these targets are highly conserved in A. baumannii and the closely related A. pittii and A. lactucae, they could serve as potential therapeutic targets for developing new antivirulence agents to combat these pathogens.