Modification of the 1-phosphate group during biosynthesis of Capnocytophaga canimorsus lipid A

Francesco Renzi, Ulrich Zaehringer, C.E. Chandler, R. K. Ernst, Guy Cornelis, Simon Ittig

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Abstract

Capnocytophaga canimorsus, a commensal bacterium of dog's mouth flora causing severe infections in humans after dog bites or scratches, has a lipopolysaccharide (LPS, endotoxin) with low-inflammatory lipid A. In particular it contains a phosphoethanolamine (P-Etn) instead of a free phosphate group at the C-1 position of the lipid A backbone, usually present in highly toxic enterobacterial Gram-negative lipid A. Here we show that the C. canimorsus genome comprises a single operon encoding a lipid A 1-phosphatase (LpxE) and a lipid A 1 P-Etn transferase (EptA). This suggests that lipid A is modified during biosynthesis after completing acylation of the backbone by removal of the 1-phosphate and subsequent addition of a P-Etn group. As endotoxicity of lipid A is known to depend largely on the degree of unsubstituted or unmodified phosphate residues, deletion of lpxE or eptA led to mutants lacking the P-Etn group, with consequently increased endotoxicity and decreased resistance to cationic antimicrobial peptides (CAMP). Consistent with the proposed sequential biosynthetic mechanism, the endotoxicity and CAMP resistance of a double deletion mutant of lpxE-eptA was similar to that of a single lpxE mutant. Finally, the proposed enzymatic activities of LpxE and EptA based on sequence similarity could be successfully validated by MS-based analysis of lipid A isolated from corresponding deletion mutant strains.
Original languageEnglish
Article numberdoi: 10.1128/IAI.01006-15
Pages (from-to)550-561
JournalInfection and Immunity
Volume84
Issue number2
DOIs
Publication statusPublished - 7 Dec 2015

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