Copy Number of an Integron-Encoded Antibiotic Resistance Locus Regulates a Virulence and Opacity Switch in Acinetobacter baumannii AB5075.

摘要: ABSTRACT We describe a novel genetic mechanism in which tandem amplification of plasmid-borne integron regulates virulence, opacity variation, and global gene expression by altering levels putative small RNA (sRNA) Acinetobacter baumannii AB5075. Copy number this amplified locus correlated with the rate switching between virulent opaque (VIR-O) avirulent translucent (AV-T) cells. found that prototypical VIR-O colonies, exhibit high visible sectoring AV-T cells 24 h growth, harbor two copies locus. However, subset colonies did not form sectors within were to only one copy. The decreased designated low-switching (LSO) variants 3-log decrease relative VIR-O. Overexpression studies revealed element regulating was localized 5′ end aadB Northern blotting indicated an sRNA approximately 300 nucleotides (nt) is encoded region likely responsible for AV-T. ∼300-nt also affect as LSO variant exhibited virulence during murine lung infections. Global transcriptional profiling >100 genes differentially expressed variants, suggesting may act regulator. Several cells, potentially explaining their virulence. IMPORTANCEAcinetobacter remains leading cause hospital-acquired Widespread multidrug resistance species has prompted WHO name carbapenem-resistant A. its top priority research development new antibiotics. Many strains undergo high-frequency switch, attractive target therapeutics targeting pathogen. This study reports controlling frequency strain from positively influenced copy antibiotic on composite integron. Our data suggest encodes switching. Low-switching single locus, increases our understanding critical phenotypic while identifying potential targets virulence-based treatments.