Brucella abortus depends on L-serine biosynthesis for intracellular proliferation

RÉVORA, VIRGINIA; COMERCI, DIEGO J.; MARCHESINI, MARÍA INÉS

INFECTION AND IMMUNITY

AMER SOC MICROBIOLOGY

Año: 2019

0019-9567

L-serine is a non-essential amino acid and a key intermediate in several relevant metabolic pathways. In bacteria, the major source of L-serine is the phosphorylated pathway, which comprises three enzymes: D-3-phosphoglycerate dehydrogenase (PGDH; SerA), phosphoserine amino transferase (PSAT; SerC), and L-phosphoserine phosphatase (PSP; SerB). Brucella abortus genome encodes two PGDHs (SerA-1 and SerA-2), involved the first step in L-serine biosynthesis, one PSAT and one PSP, responsible for the second and third steps, respectively. In this study, we demonstrate that the double mutant serA-1_serA-2, and the single mutants serC and serB are auxotrophic for L-serine. These auxotrophic mutants can be internalized but are unable to replicate in HeLa cells and in J77A.1 macrophage-like cells. Replication defects of auxotrophic mutants can be reverted by cell medium supplementation with L-serine at early times post-infection. Additionally, serB mutant is attenuated in the murine intraperitoneal infection model and has an altered lipid composition, since lack of L-serine abrogates phosphatidylethanolamine synthesis in this strain. Taken together, these results reveal that limited availability of L-serine within the host cell impairs proliferation of the auxotrophic strains, highlighting the relevance of this biosynthetic pathway in Brucella pathogenicity.