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The K1 Capsular Polysaccharide of Acinetobacter baumannii Strain 307-0294 Is a Major Virulence Factor

Author:
Russo, Thomas A., Luke, Nicole R., Beanan, Janet M., Olson, Ruth, Sauberan, Shauna L., MacDonald, Ulrike, Schultz, L. Wayne, Umland, Timothy C., Campagnari, Anthony A.
Source:
Infection and immunity 2010 v.78 no.9 pp. 3993-4000
ISSN:
0019-9567
Subject:
Acinetobacter baumannii, ascites, blood serum, drugs, essential genes, flow cytometry, humans, models, monoclonal antibodies, multiple drug resistance, mutants, outer membrane proteins, pathogenesis, pathogens, phenotype, polymerization, rats, transposons, tyrosine, virulence
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.
Agid:
286439