Abstract
In the O1 strain of Klebsiella, the lipopolysaccharide (LPS) O-antigen is composed of D-galactan I and D-galactan II. Although the composition of the O1 antigen of Klebsiella was resolved more than two decades, the genetic locus involved in the biosynthesis of D-galactan II and the role of D-galactan II in bacterial pathogenesis remain unclear. Here, we report the identification of the D-galactan II-synthesizing genes by screening a transposon mutant library of an acapsulated Klebsiella pneumoniae O1 strain with bacteriophage. K. pneumoniae strain deleted for wbbY exhibited abrogated D-galactan II production; altered serum resistance and attenuation of virulence. Serologic analysis of K. pneumoniae clinical isolates demonstrated that D-galactan II was more prevalent in community-acquired pyogenic liver abscess (PLA)—causing strains than in non-tissue-invasive strains. WbbY homologs, WbbZ homologs, and lipopolysaccharide structures based on D-galactan II also were present in several Gram-negative bacteria. Immunization of mice with the magA-mutant (K−1 O1) (that is, with a LPS D-galactan II-producing strain) provided protection against infection with an O1:K2 PLA strain. Our findings indicate that both WbbY and WbbZ homologs are sufficient for the synthesis of D-galactan II. D-galactan II represents an immunodominant antigen; is conserved among multiple species of Gram-negative bacteria and could be a useful vaccine candidate.
Highlights
Several Gram-negative bacterial pathogens decorate their surfaces with exopolysaccharide (EPS), including capsular polysaccharide (CPS) and lipopolysaccharide (LPS)
We identified and characterized the genetic locus involved in the biosynthesis of DGal D-galactan II (II) of the O1 antigen; examined the distribution of the D-Gal II antigen in pyogenic liver abscess (PLA) and non-tissue-invasive K. pneumoniae clinical isolates; investigated the distribution of the D-Gal II-synthesizing genes in E. coli O19 and other Gram-negative bacteria; explored the role of D-Gal II of K. pneumoniae in serum-killing and the pathogenesis of bacteremia; and investigated whether antiserum raised against LPS D-Gal II protected against D-Gal II-producing bacterial infection
This result demonstrates that bacteriophage O1-1 did not infect the encapsulated K. pneumoniae bacteria, presumably due to masking of the receptor by CPS
Summary
Several Gram-negative bacterial pathogens decorate their surfaces with exopolysaccharide (EPS), including capsular polysaccharide (CPS) and lipopolysaccharide (LPS). LPS is composed of lipid A, core oligosaccharide, and O antigenic polysaccharide. The O antigen contributes to serum resistance of several Gramnegative bacteria and is a determinant of bacterial virulence (Krishnapillai, 1971; Taylor, 1976; Schneider et al, 1982; Tomas et al, 1986; Hong and Payne, 1997; Hsieh et al, 2012). K. pneumoniae is an opportunistic pathogen that causes several kinds of infections, including pneumonia, bacteremia, urinary tract infection, and community-acquired pyogenic liver abscess (PLA) (Podschun and Ullmann, 1998; Ko et al, 2002; Ramphal and Ambrose, 2006; Tsai et al, 2008).
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