AbCro, a novel transcription factor, promotes biofilm formation and virulence in Acinetobacter baumannii

The emergence of highly virulent Acinetobacter baumannii strains has increased patient mortality and complicated clinical prognosis, motivating the development of novel control strategies. Genomic analysis of the clinical isolate AB43 revealed a protein, AbCro, which is homologous to the bacteriophage transcription factor Cro. In this study, an Abcro deletion mutant and its complemented strain were constructed. Our results showed that the deletion of Abcro significantly reduced the biofilm formation, attenuated virulence in both Galleria mellonella and mice, and alleviated pathological damage to lung tissues in mice. Transcriptome analysis revealed that the expression of both otsA and otsB was significantly downregulated in the AB43Δcro strain. These genes encode trehalose-6-phosphate synthase (OtsA) and trehalose-6-phosphate phosphatase (OtsB), respectively, which sequentially catalyze trehalose biosynthesis - a key stress protectant in microorganisms. The otsA was located 3’ to the otsB and the genes overlapped by 13 nucleotides, forming the otsBA operon. The purified AbCro was able to bind to the promoter region of the operon. These results demonstrate that AbCro may activate the trehalose biosynthesis pathway otsBA, consequently enhancing the virulence of A. baumannii. Altogether, these findings provide novel theoretical foundations and potential therapeutic targets for controlling A. baumannii infections.