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

ABSTRACT: 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 colonization and biofilm formation on catheters, which become coated with fibrinogen upon insertion. We developed a protein subunit vaccine against Abp1D_RBD and Abp2D_RBD and showed that vaccination significantly reduced bladder bacterial titers in a mouse model of CAUTI. We then determined that immunity to Abp2D_RBD alone was sufficient for protection. Mechanistically, we defined the B cell response to Abp2D_RBD vaccination and demonstrated that immunity was transferrable to naïve mice through passive immunization with Abp2D_RBD-immune sera. This work represents a novel strategy in the prevention of A. baumannii CAUTI and has an important role to play in the global fight against antimicrobial resistance.

SUBMITTER: Timm MR

PROVIDER: S-EPMC10441454 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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

Timm Morgan R MR Tamadonfar Kevin O KO Nye Taylor M TM Pinkner Jerome S JS Dodson Karen W KW Ellebedy Ali H AH Hultgren Scott J SJ

Research square 20230810

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 colonization and biofilm formation on catheters, which become coated with fibrinogen upon insertion. We developed a protein subunit va ...[more]

PMID: 37609304

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Project description:The increasing antibiotic resistance of pathogenic Escherichia coli species and the absence of a pan-protective vaccine pose major health concerns. We recently identified, by subtractive reverse vaccinology, nine Escherichia coli antigens that protect mice from sepsis. In this study, we characterized one of them, ECOK1_0290, named FdeC (factor adherence E. coli) for its ability to mediate E. coli adhesion to mammalian cells and extracellular matrix. This adhesive propensity was consistent with the X-ray structure of one of the FdeC domains that shows a striking structural homology to Yersinia pseudotuberculosis invasin and enteropathogenic E. coli intimin. Confocal imaging analysis revealed that expression of FdeC on the bacterial surface is triggered by interaction of E. coli with host cells. This phenotype was also observed in bladder tissue sections derived from mice infected with an extraintestinal strain. Indeed, we observed that FdeC contributes to colonization of the bladder and kidney, with the wild-type strain outcompeting the fdeC mutant in cochallenge experiments. Finally, intranasal mucosal immunization with recombinant FdeC significantly reduced kidney colonization in mice challenged transurethrally with uropathogenic E. coli, supporting a role for FdeC in urinary tract infections. Pathogenic Escherichia coli strains are involved in a diverse spectrum of diseases, including intestinal and extraintestinal infections (urinary tract infections and sepsis). The absence of a broadly protective vaccine against all these E. coli strains is a major problem for modern society due to high costs to health care systems. Here, we describe the structural and functional properties of a recently reported protective antigen, named FdeC, and elucidated its putative role during extraintestinal pathogenic E. coli infection by using both in vitro and in vivo infection models. The conservation of FdeC among strains of different E. coli pathotypes highlights its potential as a component of a broadly protective vaccine against extraintestinal and intestinal E. coli infections.

Dataset Information

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

Publications

Vaccination with <i>Acinetobacter baumannii</i> adhesin Abp2D provides protection against catheter-associated urinary tract infection.

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Dataset Information

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

Publications

Vaccination with &lt;i&gt;Acinetobacter baumannii&lt;/i&gt; adhesin Abp2D provides protection against catheter-associated urinary tract infection.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

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Vaccination with <i>Acinetobacter baumannii</i> adhesin Abp2D provides protection against catheter-associated urinary tract infection.