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Hfq orchestrates a robust RNA-RNA interaction network in Acinetobacter baumannii
Journal article   Open access   Peer reviewed

Hfq orchestrates a robust RNA-RNA interaction network in Acinetobacter baumannii

Valerie Intorcia, Mikaela N. Daum, Boyang Cheng, Simon L. Dove and Michael J. Gebhardt
mBio, Vol.17(1), e0323125
01/14/2026
DOI: 10.1128/mbio.03231-25
PMCID: PMC12802169
PMID: 41405210
url
https://doi.org/10.1128/mbio.03231-25View
Published (Version of record) Open Access

Abstract

Across bacteria, RNA binding proteins, such as Hfq, often play a key role in facilitating post-transcriptional regulation by chaperoning interactions between small regulatory RNAs (sRNAs) and their mRNA targets. Acinetobacter baumannii, a problematic gram-negative bacterial pathogen, produces over a hundred sRNAs, of which only a few have experimentally validated mRNA targets. While previous studies have identified hfq as a candidate essential gene in the model multidrug-resistant A. baumannii strain AB5075, the role of Hfq in mediating the regulatory effects of sRNAs remains largely unexplored. Here, we use RIL-seq to identify Hfq-associated sRNA-mRNA interaction partners in strain AB5075. Our results indicate that A. baumannii Hfq coordinates a robust network of RNA-RNA interactions. We detected RNA interactions with 98 distinct sRNA species, including nearly 40 previously undescribed sRNAs. The results further indicate that A. baumannii utilizes sRNAs to regulate the expression of numerous transcripts that encode virulence factors and antibiotic resistance determinants. Collectively, our study provides new insights into the regulatory potential for dozens of sRNAs in A. baumannii and highlights the importance of post-transcriptional regulation in this emerging pathogen.IMPORTANCEAcinetobacter baumannii represents a burgeoning threat to human health and consistently ranks as a critical pathogen by the World Health Organization due to extensive antimicrobial resistance among clinical isolates. While much effort has focused on understanding how A. baumannii acquires antimicrobial resistance traits, our knowledge of key processes governing gene expression in this organism is lacking. In particular, very little is known regarding post-transcriptional regulation in A. baumannii. Here, we demonstrate that Hfq, a highly conserved RNA chaperone, coordinates the regulatory activities for nearly 100 small regulatory RNAs (sRNAs), including many that have not been described before. We also find that several Hfq-associated sRNAs directly regulate mRNA transcripts, which encode antibiotic resistance determinants and virulence factors. Collectively, our study provides evidence for the existence of a complex post-transcriptional regulatory network in A. baumannii and offers new insights into how the organism uses Hfq and sRNAs to coordinate gene expression.
 Bacterial Gene Regulation Bacterial Genetics Gene Expression Control Gene Regulation in Bacteria Microbial Pathogenesis and Immunology Microbial Physiology and Genetics Molecular and Cellular Biology Regulatory Networks Research Article Small Rnas and Gene Regulation Transcriptional and Translational Control

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