AUTHOR=Aragón-Aranda Beatriz , Palacios-Chaves Leyre , Salvador-Bescós Miriam , de Miguel María Jesús , Muñoz Pilar M. , Vences-Guzmán Miguel Ángel , Zúñiga-Ripa Amaia , Lázaro-Antón Leticia , Sohlenkamp Christian , Moriyón Ignacio , Iriarte Maite , Conde-Álvarez Raquel 

TITLE=The Phospholipid N-Methyltransferase and Phosphatidylcholine Synthase Pathways and the ChoXWV Choline Uptake System Involved in Phosphatidylcholine Synthesis Are Widely Conserved in Most, but Not All Brucella Species

JOURNAL=Frontiers in Microbiology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.614243

DOI=10.3389/fmicb.2021.614243

ISSN=1664-302X

ABSTRACT=<p>The brucellae are facultative intracellular bacteria with a cell envelope rich in phosphatidylcholine (PC). PC is abundant in eukaryotes but rare in prokaryotes, and it has been proposed that <italic>Brucella</italic> uses PC to mimic eukaryotic-like features and avoid innate immune responses in the host. Two PC synthesis pathways are known in prokaryotes: the PmtA-catalyzed trimethylation of phosphatidylethanolamine and the direct linkage of choline to CDP-diacylglycerol catalyzed by the PC synthase Pcs. Previous studies have reported that <italic>B. abortus</italic> and <italic>B. melitensis</italic> possess non-functional PmtAs and that PC is synthesized exclusively <italic>via</italic> Pcs in these strains. A putative choline transporter ChoXWV has also been linked to PC synthesis in <italic>B. abortus</italic>. Here, we report that Pcs and Pmt pathways are active in <italic>B. suis</italic> biovar 2 and that a bioinformatics analysis of <italic>Brucella</italic> genomes suggests that PmtA is only inactivated in <italic>B. abortus</italic> and <italic>B. melitensis</italic> strains. We also show that ChoXWV is active in <italic>B. suis</italic> biovar 2 and conserved in all brucellae except <italic>B. canis</italic> and <italic>B. inopinata.</italic> Unexpectedly, the experimentally verified ChoXWV dysfunction in <italic>B. canis</italic> did not abrogate PC synthesis in a PmtA-deficient mutant, which suggests the presence of an unknown mechanism for obtaining choline for the Pcs pathway in <italic>Brucella</italic>. We also found that ChoXWV dysfunction did not cause attenuation in <italic>B. suis</italic> biovar 2. The results of these studies are discussed with respect to the proposed role of PC in <italic>Brucella</italic> virulence and how differential use of the Pmt and Pcs pathways may influence the interactions of these bacteria with their mammalian hosts.</p>