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

Renzi, Francesco and Zähringer, Ulrich and Chandler, Courtney E. and Ernst, Robert K. and Cornelis, Guy R. and Ittig, Simon J.. (2016) Modification of the 1-phosphate group during biosynthesis of Capnocytophaga canimorsus lipid A. Infection and immunity, 84 (2). pp. 550-561.

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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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Cell Biology (Nigg)
UniBasel Contributors:Ittig, Simon Josef
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Society for Microbiology
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:23 Aug 2016 08:11
Deposited On:23 Aug 2016 08:11

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