Exploring VirF, an AraC/XylS Family Regulator in Acinetobacter baumannii

Acinetobacter baumannii is a major cause of nosocomial infections and a growing public health threat due to its resistance to multiple antibiotics. As antibiotic options diminish, targeting virulence factors that drive pathogenesis presents a promising alternative therapeutic approach. A. baumannii utilizes a diverse array of virulence factors, yet many pathogenesis regulatory mechanisms remain poorly understood. Identifying new regulators can unveil novel therapeutic targets. AraC/XylS family transcriptional regulators (AFTRs) play key roles in controlling virulence, stress responses, and metabolism in pathogens such as Shigella flexneri, Escherichia coli, Pseudomonas aeruginosa, and Vibrio cholerae. We identified a putative AFTR in A. baumannii, designated virF, and hypothesize it may function as a virulence regulator. Structural modeling revealed conserved AFTR features, including a DNA-binding domain and a jelly roll-folded companion domain, supporting a potential regulatory role. To assess its relevance, we performed a conservation analysis of virF across a broad panel of clinical isolates. Strikingly, virF was found to be highly conserved, despite the well-documented genomic plasticity of A. baumannii. This high level of conservation across diverse clinical strains strongly suggests a crucial role in the bacterium’s fitness or pathogenicity, and highlights virF as a clinically relevant target for anti-virulence strategies. To explore its function, we are generating virF deletion mutants using a markerless, double-homologous recombination method with counter-selection. Ongoing studies aim to assess the effect of virF disruption on virulence-associated phenotypes and host-pathogen interactions. Our findings may uncover a conserved, druggable regulator essential to A. baumannii virulence, with potential implications for novel therapeutic development.