<p>Catheter-associated urinary tract infections (CAUTIs) contribute greatly to the burden of healthcare-associated infections. <i>Acinetobacter baumannii</i> is a Gram-negative bacterium with high levels of antibiotic resistance that is of increasing concern as a CAUTI pathogen. <i>A. baumannii</i> expresses fibrinogen-binding adhesins (Abp1D and Abp2D) that mediate biofilm formation on catheters, which become coated with fibrinogen upon insertion. Here we develop a protein subunit vaccine against the Abp1D and Abp2D receptor binding domains (RBD) and show that vaccination significantly reduces bacterial titers in a female mouse model of CAUTI. We further demonstrate that immunity to Abp2D<sub>RBD</sub> alone is sufficient for protection. Mechanistically, we define the B cell response to Abp2D<sub>RBD</sub> vaccination, demonstrate that passive immunization with Abp2D<sub>RBD</sub>-immune serum transfers immunity to naïve mice, and show that Abp2D<sub>RBD</sub>-immune serum inhibits bacterial binding to fibrinogen-coated catheters. This work represents an antibiotic-sparing strategy for the prevention of <i>A. baumannii</i> CAUTI which has an important role in the global fight against antimicrobial resistance.</p>

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Vaccination with Acinetobacter baumannii adhesin Abp2D provides protection against catheter-associated urinary tract infection

  • Morgan R. Timm,
  • Kevin O. Tamadonfar,
  • Taylor M. Nye,
  • Jesús Bazán Villicaña,
  • Jerome S. Pinkner,
  • Karen W. Dodson,
  • Ali H. Ellebedy,
  • Scott J. Hultgren

摘要

Catheter-associated urinary tract infections (CAUTIs) contribute greatly to the burden of healthcare-associated infections. Acinetobacter baumannii is a Gram-negative bacterium with high levels of antibiotic resistance that is of increasing concern as a CAUTI pathogen. A. baumannii expresses fibrinogen-binding adhesins (Abp1D and Abp2D) that mediate biofilm formation on catheters, which become coated with fibrinogen upon insertion. Here we develop a protein subunit vaccine against the Abp1D and Abp2D receptor binding domains (RBD) and show that vaccination significantly reduces bacterial titers in a female mouse model of CAUTI. We further demonstrate that immunity to Abp2DRBD alone is sufficient for protection. Mechanistically, we define the B cell response to Abp2DRBD vaccination, demonstrate that passive immunization with Abp2DRBD-immune serum transfers immunity to naïve mice, and show that Abp2DRBD-immune serum inhibits bacterial binding to fibrinogen-coated catheters. This work represents an antibiotic-sparing strategy for the prevention of A. baumannii CAUTI which has an important role in the global fight against antimicrobial resistance.