Identification and characterization of a glycosyltransferase involved in Acinetobacter baumannii lipopolysaccharide core biosynthesis.
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.
Luke
Nicole R
NR
Department of Microbiology, State University of New York at Buffalo, Buffalo, New York 14214, USA.
Sauberan
Shauna L
SL
Russo
Thomas A
TA
Beanan
Janet M
JM
Olson
Ruth
R
Loehfelm
Thomas W
TW
Cox
Andrew D
AD
St Michael
Frank
F
Vinogradov
Evgeny V
EV
Campagnari
Anthony A
AA
D000151:Acinetobacter Infections / Q000382:microbiology; D040981:Acinetobacter baumannii / Q000201:enzymology* / Q000235:genetics; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001770:Blood Bactericidal Activity; D015169:Colony Count, Microbial; D017124:Conserved Sequence; D055786:Gene Knockout Techniques; D005816:Genetic Complementation Test; D016695:Glycosyltransferases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008070:Lipopolysaccharides / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D050296:Microbial Viability; D016254:Mutagenesis, Insertional; D051381:Rats; D017386:Sequence Homology, Amino Acid; D018461:Soft Tissue Infections / Q000382:microbiology
D001426:Bacterial Proteins; D008070:Lipopolysaccharides; D016695:Glycosyltransferases