Abstract
Lipopolysaccharide (LPS) is one of the main constituents of the Gram-negative bacterial outer membrane. It usually consists of a highly variable O-antigen, a less variable core oligosaccharide, and a highly conserved lipid moiety, designated lipid A. Several bacteria are capable of modifying their lipid A architecture in response to external stimuli. The outer membrane-localized lipid A 3-O-deacylase, encoded by the pagL gene of Salmonella enterica serovar Typhimurium, removes the fatty acyl chain from the 3 position of lipid A. Although a similar activity was reported in some other Gram-negative bacteria, the corresponding genes could not be identified. Here, we describe the presence of pagL homologs in a variety of Gram-negative bacteria. Although the overall sequence similarity is rather low, a conserved domain could be distinguished in the C-terminal region. The activity of the Pseudomonas aeruginosa and Bordetella bronchiseptica pagL homologs was confirmed upon expression in Escherichia coli, which resulted in the removal of an R-3-hydroxymyristoyl group from lipid A. Upon deacylation by PagL, E. coli lipid A underwent another modification, which was the result of the activity of the endogenous palmitoyl transferase PagP. Furthermore, we identified a conserved histidine-serine couple as active site residues, suggesting a catalytic mechanism similar to serine hydrolases. The biological function of PagL remains unclear. However, because PagL homologs were found in both pathogenic and nonpathogenic species, PagL-mediated deacylation of lipid A probably does not have a dedicated role in pathogenicity.
Highlights
Lipopolysaccharide (LPS) is one of the main constituents of the Gram-negative bacterial outer membrane
The activity of the Pseudomonas aeruginosa and Bordetella bronchiseptica pagL homologs was confirmed upon expression in Escherichia coli, which resulted in the removal of an R-3-hydroxymyristoyl group from lipid A
In Escherichia coli, it consists of a 1,4Ј-bisphosphorylated -1,6-linked glucosamine disaccharide, which is replaced by R-3-hydroxymyristic acid residues at positions 2, 3, 2Ј, and 3Ј via ester or amide linkage
Summary
Lipopolysaccharide (LPS) is one of the main constituents of the Gram-negative bacterial outer membrane. Homologs of the PhoP/PhoQ and PmrA/PmrB systems have been identified in other Gram-negative bacteria, including E. coli, Yersinia pestis, and Pseudomonas aeruginosa [13, 14]. Typhimurium, Bordetella pertussis, Bordetella bronchiseptica, Bordetella parapertussis, Legionella pneumophila, E. coli, and Y. pestis [19, 21] Another outer membrane-localized lipid A-modifying enzyme is the 3-O-deacylase PagL [22]. Some other Gram-negative bacteria, including P. aeruginosa [14], R. leguminosarum [23], Helicobacter pylori [24], and Porhyromonas gingivalis [25] contain 3-O-deacylated lipid A species, suggesting that these organisms contain enzymes with an activity similar to that of PagL. The limited sequence similarity among the various proteins was used to identify active site residues
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