Identification of a Novel Ciprofloxacin Tolerance Gene, , Which Contributes to Filamentation in Acinetobacter baumannii.

Fluoroquinolones are one of the most prescribed broad-spectrum antibiotics. However, their effectiveness is being compromised by high rates of resistance in clinically important organisms, including We sought to investigate the transcriptomic and proteomic responses of the clinical strain AB5075-UW upon exposure to subinhibitory concentrations of ciprofloxacin. Our transcriptomics and proteomics analyses found that the most highly expressed genes and proteins were components of the intact prophage The next most highly expressed gene (and its protein product) under ciprofloxacin stress was a hypothetical gene, ABUW_0098, named here the profloxacin olerance () gene. Disruption of this gene resulted in higher susceptibility to ciprofloxacin, and complementation of the mutant with a cloned gene restored ciprofloxacin tolerance to parental strain levels. Microscopy studies revealed that is essential for filamentation during ciprofloxacin stress in Sequence analysis of indicates the encoded protein is likely to be localized to the cell membrane. Orthologs of are found widely in the genomes of species from the family and are well conserved in species, suggesting an important role. With these findings taken together, this study has identified a new gene conferring tolerance to ciprofloxacin, likely by enabling filamentation in response to the antibiotic.