Abstract
Multidrug resistant (MDR) Acinetobacter baumannii poses a growing threat to global health. Research on Acinetobacter pathogenesis has primarily focused on pneumonia and bloodstream infections, even though one in five A. baumannii strains are isolated from urinary sites. In this study, we highlight the role of A. baumannii as a uropathogen. We develop the first A. baumannii catheter-associated urinary tract infection (CAUTI) murine model using UPAB1, a recent MDR urinary isolate. UPAB1 carries the plasmid pAB5, a member of the family of large conjugative plasmids that represses the type VI secretion system (T6SS) in multiple Acinetobacter strains. pAB5 confers niche specificity, as its carriage improves UPAB1 survival in a CAUTI model and decreases virulence in a pneumonia model. Comparative proteomic and transcriptomic analyses show that pAB5 regulates the expression of multiple chromosomally-encoded virulence factors besides T6SS. Our results demonstrate that plasmids can impact bacterial infections by controlling the expression of chromosomal genes.
Highlights
Multidrug resistant (MDR) Acinetobacter baumannii poses a growing threat to global health
To investigate this significant manifestation of A. baumannii disease, we develop a murine model of A. baumannii catheter-associated urinary tract infection (CAUTI) using a recent MDR urinary tract infections (UTI) isolate, UPAB1
To expand our investigation globally, we performed a systematic review of clinical studies published since 1995, which document the anatomical site of isolation of A. baumannii or Acinetobacter calcoaceticus-baumannii complex” (Acbc) specimens
Summary
Multidrug resistant (MDR) Acinetobacter baumannii poses a growing threat to global health. We develop the first A. baumannii catheter-associated urinary tract infection (CAUTI) murine model using UPAB1, a recent MDR urinary isolate. The Gram-negative bacterium Acinetobacter baumannii is generally considered an opportunistic pathogen with no specificity for a particular niche As a pathogen, it is primarily associated with nosocomial infections, mainly hospital acquired pneumonia, bacteremia, soft tissue infections, and urinary tract infections (UTI)[5], cases of community acquired infections have been described[6]. We report that up to one-fifth of A. baumannii isolates are obtained from urinary sources, according to a local retrospective study and a systematic review of literature from the last 25 years To investigate this significant manifestation of A. baumannii disease, we develop a murine model of A. baumannii CAUTI using a recent MDR UTI isolate, UPAB1. We demonstrate that UPAB1 is able to establish early implant and bladder colonization, dependent on chaperone-usher pathway (CUP) pili
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