title: Evaluation of the trimeric autotransporter Ata as a vaccine candidate against Acinetobacter baumannii infections.
abstract: Acinetobacter baumannii is a multidrug-resistant (MDR) nosocomial pathogen for which immunotherapeutic alternatives are needed. We previously identified a surface autotransporter of A. baumannii, Ata, that bound to various extracellular matrix/basal membrane proteins and was required for full virulence, biofilm formation, and the adhesion of A. baumannii to collagen type IV. We show here that Ata binding to collagen type IV was inhibited by antibodies to Ata. In addition, in the presence of complement and polymorphonuclear cells (PMNs), antibodies to Ata were highly opsonic against A. baumannii ATCC 17978 and showed low to moderate killing activity against four heterologous A. baumannii strains, whereas in the absence of PMNs, antibody to Ata efficiently promoted complement-dependent bactericidal killing of all of the tested A. baumannii isolates. Using a pneumonia model of infection in both immunocompetent and immunocompromised mice, we found that, compared to normal rabbit sera, antisera to Ata significantly reduced the levels of A. baumannii ATCC 17978 and two MDR strains in the lungs of infected mice. The ability of Ata to engender anti-adhesive, bactericidal, opsonophagocytic, and protective antibodies validates its potential use as an antigenic target against MDR A. baumannii infections.
authors: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors: Leticia V
authors: LV
authors: Bentancor
authors: Abhisek
authors: A
authors: Routray
authors: Cagla
authors: C
authors: Bozkurt-Guzel
authors: Ana
authors: A
authors: Camacho-Peiro
authors: Gerald B
authors: GB
authors: Pier
authors: Tomás
authors: T
authors: Maira-Litrán
mesh_terms: D000151:Acinetobacter Infections / Q000517:prevention & control*; D040981:Acinetobacter baumannii / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001422:Bacterial Adhesion; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001428:Bacterial Vaccines / Q000276:immunology*; D024141:Collagen Type IV; D024901:Drug Resistance, Multiple, Bacterial; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D008565:Membrane Proteins / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018410:Pneumonia, Bacterial / Q000382:microbiology / Q000517:prevention & control; D011817:Rabbits
chemical_list: D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D024141:Collagen Type IV; D008565:Membrane Proteins