title: The K1 capsular polysaccharide from Acinetobacter baumannii is a potential therapeutic target via passive immunization.
abstract: The emergence of extremely resistant and panresistant Gram-negative bacilli, such as Acinetobacter baumannii, requires consideration of nonantimicrobial therapeutic approaches. The goal of this report was to evaluate the K1 capsular polysaccharide from A. baumannii as a passive immunization target. Its structure was determined by a combination of mass spectrometric and nuclear magnetic resonance (NMR) techniques. Molecular mimics that might raise the concern for autoimmune disease were not identified. Immunization of CD1 mice demonstrated that the K1 capsule is immunogenic. The monoclonal antibody (MAb) 13D6, which is directed against the K1 capsule from A. baumannii, was used to determine the seroprevalence of the K1 capsule in a collection of 100 A. baumannii strains. Thirteen percent of the A. baumannii isolates from this collection were seroreactive to MAb 13D6. Opsonization of K1-positive strains, but not K1-negative strains, with MAb 13D6 significantly increased neutrophil-mediated bactericidal activity in vitro (P < 0.05). Lastly, treatment with MAb 13D6 3 and 24 h after bacterial challenge in a rat soft tissue infection model resulted in a significant decrease in the growth/survival of a K1-positive strain compared to that of a K1-negative strain or to treatment with a vehicle control (P < 0.0001). These data support the proof of principle that the K1 capsule is a potential therapeutic target via passive immunization. Other serotypes require assessment, and pragmatic challenges exist, such as the need to serotype infecting strains and utilize serotype-specific therapy. Nonetheless, this approach may become an important therapeutic option with increasing antimicrobial resistance and a diminishing number of active antimicrobials.
authors.affiliation: Veterans Administration Western New York Healthcare System, University at Buffalo-State University of New York, Buffalo, New York, USA. trusso@acsu.buffalo.edu
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Russo
authors.forename: Janet M
authors.initials: JM
authors.lastname: Beanan
authors.forename: Ruth
authors.initials: R
authors.lastname: Olson
authors.forename: Ulrike
authors.initials: U
authors.lastname: MacDonald
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Cox
authors.forename: Frank
authors.initials: F
authors.lastname: St Michael
authors.forename: Evgeny V
authors.initials: EV
authors.lastname: Vinogradov
authors.forename: Brad
authors.initials: B
authors.lastname: Spellberg
authors.forename: Nicole R
authors.initials: NR
authors.lastname: Luke-Marshall
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Campagnari
mesh_terms: D000151:Acinetobacter Infections / Q000517:prevention & control*; D040981:Acinetobacter baumannii / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000942:Antigens, Bacterial; D016667:Bacterial Capsules / Q000235:genetics / Q000378:metabolism*; D001428:Bacterial Vaccines / Q000276:immunology*; D000939:Epitopes; D005434:Flow Cytometry; D015964:Gene Expression Regulation, Bacterial; D007116:Immunization, Passive; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D011135:Polysaccharides, Bacterial; D051381:Rats; D020318:Rats, Long-Evans
chemical_list: D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D000939:Epitopes; D011135:Polysaccharides, Bacterial; C036962:capsular polysaccharide K1