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

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Résumé

Capnocytophaga canimorsus, a commensal bacterium of dog's mouth flora causing severe infections in humans after dog bites or scratches [1], has a lipopolysaccharide (LPS, endotoxin) with low-inflammatory lipid A [2]. 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 phosphorylation, 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. [1] Butler T. 2015. Capnocytophaga canimorsus: an emerging cause of sepsis, meningitis, and post-splenectomy infection after dog bites. European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology 34:1271-1280. [2] Ittig S., Lindner B., Stenta M., Manfredi P., Zdorovenko E., Knirel Y.A., dal Peraro M., Cornelis G.R., Zähringer U. 2012. The lipopolysaccharide from Capnocytophaga canimorsus reveals an unexpected role of the core-oligosaccharide in MD-2 binding. PLoS Pathogens 8(5) e1002667.
langue originaleAnglais
Etat de la publicationPublié - 25 oct. 2015
EvénementThe 26th Joint Glycobiology Meeting - Institut Pasteur Lille, Lille, France
Durée: 25 oct. 201527 oct. 2015

Réunion

RéunionThe 26th Joint Glycobiology Meeting
PaysFrance
La villeLille
période25/10/1527/10/15

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