Gil Ramírez, Yolanda

Profile Picture

Email Address

person.page.identifierURI

https://academica-e.unavarra.es/handle/2454/49144

Birth Date

Job Title

Last Name

Gil Ramírez

First Name

Yolanda

person.page.departamento

Instituto de Agrobiotecnología (IdAB)

person.page.instituteName

ORCID

person.page.observainves

person.page.upna

810152

Name

Filters

20181
Reset filters

Settings

Subject: Cell envelope ×

Search Results

Now showing 1 - 1 of 1
  • Thumbnail Image
    PublicationOpen Access
    Identification of lptA, lpxE, and lpxO, three genes involved in the remodeling of Brucella cell envelope
    (Frontiers Media, 2018) Conde Álvarez, Raquel; Palacios Chaves, Leyre; Gil Ramírez, Yolanda; Salvador Bescós, Miriam; Bárcena-Varela, Marina; Aragón Aranda, Beatriz; Martínez Gómez, Estrella; Zúñiga Ripa, Amaia; Miguel López, María Jesús de; Bartholomew, Toby Leigh; Hanniffy, Sean; Grilló Dolset, María Jesús; Vences Guzmán, Miguel Ángel; Bengoechea Alonso, José Antonio; Arce Gorvel, Vilma; Gorvel, Jean-Pierre; Moriyón Uría, Ignacio; Iriarte, Maite; IdAB. Instituto de Agrobiotecnología / Agrobioteknologiako Institutua
    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.