000095045 001__ 95045
000095045 005__ 20200904094319.0
000095045 0247_ $$2doi$$a10.1074/jbc.RA118.004680
000095045 0248_ $$2sideral$$a118777
000095045 037__ $$aART-2019-118777
000095045 041__ $$aeng
000095045 100__ $$0(orcid)0000-0002-8134-0693$$aArenas, Jesús$$uUniversidad de Zaragoza
000095045 245__ $$aSubstrate specificity of the pyrophosphohydrolase LpxH determines the asymmetry of Bordetella pertussis lipid A
000095045 260__ $$c2019
000095045 5060_ $$aAccess copy available to the general public$$fUnrestricted
000095045 5203_ $$aLipopolysaccharides are anchored to the outer membrane of Gram-negative bacteria by a hydrophobic moiety known as lipid A, which potently activates the host innate immune response. Lipid A of Bordetella pertussis, the causative agent of whooping cough, displays unusual structural asymmetry with respect to the length of the acyl chains at the 3 and 3′ positions, which are 3OH-C10 and 3OH-C14 chains, respectively. Both chains are attached by the acyltransferase LpxA, the first enzyme in the lipid A biosynthesis pathway, which, in B. pertussis, has limited chain length specificity. However, this only partially explains the strict asymmetry of lipid A. In attempts to modulate the endotoxicity of B. pertussis lipid A, here we expressed the gene encoding LpxA from Neisseria meningitidis, which specifically attaches 3OH-C12 chains, in B. pertussis. This expression was lethal, suggesting that one of the downstream enzymes in the lipid A biosynthesis pathway in B. pertussis cannot handle precursors with a 3OH-C12 chain. We considered that the UDP-diacylglucosamine pyrophosphohydrolase LpxH could be responsible for this defect as well as for the asymmetry of B. pertussis lipid A. Expression of meningococcal LpxH in B. pertussis indeed resulted in new symmetric lipid A species with 3OH-C10 or 3OH-C14 chains at both the 3 and 3′ positions, as revealed by MS analysis. Furthermore, co-expression of meningococcal lpxH and lpxA resulted in viable cells that incorporated 3OH-C12 chains in B. pertussis lipid A. We conclude that the asymmetry of B. pertussis lipid A is determined by the acyl chain length specificity of LpxH.
000095045 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000095045 590__ $$a4.238$$b2019
000095045 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b87 / 297 = 0.293$$c2019$$dQ2$$eT1
000095045 592__ $$a2.283$$b2019
000095045 593__ $$aBiochemistry$$c2019$$dQ1
000095045 593__ $$aMolecular Biology$$c2019$$dQ1
000095045 593__ $$aCell Biology$$c2019$$dQ1
000095045 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000095045 700__ $$aPupo, Elder
000095045 700__ $$ade Jonge, Eline
000095045 700__ $$aPérez-Ortega, Jesús
000095045 700__ $$aSchaarschmidt, Joerg
000095045 700__ $$avan der Ley, Peter
000095045 700__ $$aTommassen, Jan
000095045 7102_ $$11009$$2773$$aUniversidad de Zaragoza$$bDpto. Patología Animal$$cÁrea Sanidad Animal
000095045 773__ $$g294, 20 (2019), 7982–7989$$pJ. biol. chem.$$tJournal of Biological Chemistry$$x0021-9258
000095045 8564_ $$s1322762$$uhttps://zaguan.unizar.es/record/95045/files/texto_completo.pdf$$yVersión publicada
000095045 8564_ $$s32426$$uhttps://zaguan.unizar.es/record/95045/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000095045 909CO $$ooai:zaguan.unizar.es:95045$$particulos$$pdriver
000095045 951__ $$a2020-09-04-08:31:24
000095045 980__ $$aARTICLE