Identification and Characterization of a Glycosyltransferase Involved in Acinetobacter baumannii Lipopolysaccharide Core Biosynthesis

• Published in: Infection and Immunity Vol. 78; no. 5; pp. 2017 - 2023
• Main Authors: Luke, Nicole R, Sauberan, Shauna L, Russo, Thomas A, Beanan, Janet M, Olson, Ruth, Loehfelm, Thomas W, Cox, Andrew D, St. Michael, Frank, Vinogradov, Evgeny V, Campagnari, Anthony A
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for Microbiology 01.05.2010; American Society for Microbiology (ASM)
• Subjects: Acinetobacter baumannii; Acinetobacter baumannii - enzymology; Acinetobacter baumannii - genetics; Acinetobacter Infections - microbiology; Animals; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Bacteriology; Biological and medical sciences; Blood Bactericidal Activity; Colony Count, Microbial; Conserved Sequence; Fundamental and applied biological sciences. Psychology; Gene Knockout Techniques; Genetic Complementation Test; Glycosyltransferases - genetics; Glycosyltransferases - metabolism; Humans; Lipopolysaccharides - biosynthesis; Mice; Mice, Inbred BALB C; Microbial Viability; Microbiology; Miscellaneous; Molecular Pathogenesis; Mutagenesis, Insertional; Rats; Sequence Homology, Amino Acid; Soft Tissue Infections - microbiology; Acinetobacter baumannii; Enzyme; Transferases; Neisseriaceae; Glycosyltransferases; Lipopolysaccharide; Bacteria; Micrococcales; Biosynthesis; Identification; Immunity
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.00016-10

Although Acinetobacter baumannii has emerged as a significant cause of nosocomial infections worldwide, there have been few investigations describing the factors important for A. baumannii persistence and pathogenesis. This paper describes the first reported identification of a glycosyltransferase, LpsB, involved in lipopolysaccharide (LPS) biosynthesis in A. baumannii. Mutational, structural, and complementation analyses indicated that LpsB is a core oligosaccharide glycosyl transferase. Using a genetic approach, lpsB was compared with the lpsB homologues of several A. baumannii strains. These analyses indicated that LpsB is highly conserved among A. baumannii isolates. Furthermore, we developed a monoclonal antibody, monoclonal antibody 13C11, which reacts to an LPS core epitope expressed by approximately one-third of the A. baumannii clinical isolates evaluated to date. Previous studies describing the heterogeneity of A. baumannii LPS were limited primarily to structural analyses; therefore, studies evaluating the correlation between these surface glycolipids and pathogenesis were warranted. Our data from an evaluation of LpsB mutant 307::TN17, which expresses a deeply truncated LPS glycoform consisting of only two 3-deoxy-D-manno-octulosonic acid residues and lipid A, suggest that A. baumannii LPS is important for resistance to normal human serum and confers a competitive advantage for survival in vivo. These results have important implications for the role of LPS in A. baumannii infections.