title: The K1 capsular polysaccharide of Acinetobacter baumannii strain 307-0294 is a major virulence factor.
abstract: Acinetobacter baumannii is a pathogen of increasing medical importance with a propensity to be multidrug resistant, thereby making treatment challenging. Little is known of virulence traits in A. baumannii. To identify virulence factors and potential drug targets, random transposon (Tn) mutants derived from the A. baumannii strain AB307-0294 were screened to identify genes essential for growth in human ascites fluid in vitro, an inflammatory exudative fluid. These studies led to the identification of two genes that were predicted to be required for capsule polymerization and assembly. The first, ptk, encodes a putative protein tyrosine kinase (PTK), and the second, epsA, encodes a putative polysaccharide export outer membrane protein (EpsA). Monoclonal antibodies used in flow cytometric and Western analyses confirmed that these genes are required for a capsule-positive phenotype. A capsule-positive phenotype significantly optimized growth in human ascites fluid, survival in human serum, and survival in a rat soft tissue infection model. Importantly, the clearance of the capsule-minus mutants AB307.30 (ptk mutant, capsule minus) and AB307.45 (epsA mutant, capsule minus) was complete and durable. These data demonstrated that the K1 capsule from AB307-0294 was an important protectin. Further, these data suggested that conserved proteins, which contribute to the capsule-positive phenotype, are potential antivirulence drug targets. Therefore, the results from this study have important biologic and translational implications and, to the best of our knowledge, are the first to address the role of capsule in the pathogenesis of A. baumannii infection.
authors.affiliation: Veterans Administration Western New York Healthcare System, Department of Medicine, Division of Infectious Diseases, University at Buffalo, 3435 Main St., Biomedical Research Building (Room 141), Buffalo, NY 14214, USA. trusso@acsu.buffalo.edu
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Russo
authors.forename: Nicole R
authors.initials: NR
authors.lastname: Luke
authors.forename: Janet M
authors.initials: JM
authors.lastname: Beanan
authors.forename: Ruth
authors.initials: R
authors.lastname: Olson
authors.forename: Shauna L
authors.initials: SL
authors.lastname: Sauberan
authors.forename: Ulrike
authors.initials: U
authors.lastname: MacDonald
authors.forename: L Wayne
authors.initials: LW
authors.lastname: Schultz
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Umland
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Campagnari
mesh_terms: D040981:Acinetobacter baumannii / Q000472:pathogenicity*; D000818:Animals; D000942:Antigens, Bacterial; D016667:Bacterial Capsules / Q000502:physiology*; D001770:Blood Bactericidal Activity; D003165:Complement System Proteins / Q000276:immunology; D006801:Humans; D011135:Polysaccharides, Bacterial; D051381:Rats; D037521:Virulence Factors / Q000502:physiology*
chemical_list: D000942:Antigens, Bacterial; D011135:Polysaccharides, Bacterial; D037521:Virulence Factors; C036962:capsular polysaccharide K1; D003165:Complement System Proteins