Publication:
Identification of lptA, lpxE, and lpxO, three genes involved in the remodeling of Brucella cell envelope

Date

2018

Authors

Conde Álvarez, Raquel
Palacios Chaves, Leyre
Salvador Bescós, Miriam
Bárcena-Varela, Marina
Aragón Aranda, Beatriz
Martínez Gómez, Estrella
Zúñiga Ripa, Amaia
Miguel López, María Jesús de
Bartholomew, Toby Leigh

Director

Publisher

Frontiers Media
Acceso abierto / Sarbide irekia
Artículo / Artikulua
Versión publicada / Argitaratu den bertsioa

Project identifier

MINECO//AGL2014-58795-C4-1-R/ES/recolecta
European Commission/FP7/291815openaire
European Commission/FP7/618162openaire

Abstract

The brucellae are facultative intracellular bacteria that cause a worldwide extended zoonosis. One of the pathogenicity mechanisms of these bacteria is their ability to avoid rapid recognition by innate immunity because of a reduction of the pathogen-associated molecular pattern (PAMP) of the lipopolysaccharide (LPS), free-lipids, and other envelope molecules. We investigated the Brucella homologs of lptA, lpxE, and lpxO, three genes that in some pathogens encode enzymes that mask the LPS PAMP by upsetting the core-lipid A charge/hydrophobic balance. Brucella lptA, which encodes a putative ethanolamine transferase, carries a frame-shift in B. abortus but not in other Brucella spp. and phylogenetic neighbors like the opportunistic pathogen Ochrobactrum anthropi. Consistent with the genomic evidence, a B. melitensis lptA mutant lacked lipid A-linked ethanolamine and displayed increased sensitivity to polymyxin B (a surrogate of innate immunity bactericidal peptides), while B. abortus carrying B. melitensis lptA displayed increased resistance. Brucella lpxE encodes a putative phosphatase acting on lipid A or on a free-lipid that is highly conserved in all brucellae and O. anthropi. Although we found no evidence of lipid A dephosphorylation, a B. abortus lpxE mutant showed increased polymyxin B sensitivity, suggesting the existence of a hitherto unidentified free-lipid involved in bactericidal peptide resistance. Gene lpxO putatively encoding an acyl hydroxylase carries a frame-shift in all brucellae except B. microti and is intact in O. anthropi. Free-lipid analysis revealed that lpxO corresponded to olsC, the gene coding for the ornithine lipid (OL) acyl hydroxylase active in O. anthropi and B. microti, while B. abortus carrying the olsC of O. anthropi and B. microti synthesized hydroxylated OLs. Interestingly, mutants in lptA, lpxE, or olsC were not attenuated in dendritic cells or mice. This lack of an obvious effect on virulence together with the presence of the intact homolog genes in O. anthropi and B. microti but not in other brucellae suggests that LptA, LpxE, or OL β-hydroxylase do not significantly alter the PAMP properties of Brucella LPS and free-lipids and are therefore not positively selected during the adaptation to intracellular life.

Description

Keywords

Lipopolysaccharide, Brucella, Lipids, Cell envelope, PAMP

Department

IdAB. Instituto de Agrobiotecnología / Agrobioteknologiako Institutua

Faculty/School

Degree

Doctorate program

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© 2018 Conde-Álvarez, Palacios-Chaves, Gil-Ramírez, Salvador-Bescós, Bárcena-Varela, Aragón-Aranda, Martínez-Gómez, Zúñiga-Ripa, de Miguel, Bartholomew, Hanniffy, Grilló, Vences-Guzmán, Bengoechea, Arce-Gorvel, Gorvel, Moriyón and Iriarte. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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