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Infect Immun. 2020 Jan 22;88(2). pii: e00840-19. doi: 10.1128/IAI.00840-19. Print 2020 Jan 22.

Brucella abortus Depends on l-Serine Biosynthesis for Intracellular Proliferation.

Author information

1
Instituto de Investigaciones Biotecnológicas Dr. Rodolfo A. Ugalde, IIB-UNSAM-CONICET, Universidad Nacional de San Martín, San Martín, Buenos Aires, Argentina.
2
Instituto de Investigaciones Biotecnológicas Dr. Rodolfo A. Ugalde, IIB-UNSAM-CONICET, Universidad Nacional de San Martín, San Martín, Buenos Aires, Argentina imarchesini@iib.unsam.edu.ar dcomerci@iib.unsam.edu.ar.
3
Comisión Nacional de Energía Atómica, Grupo Pecuario, Centro Atómico Ezeiza, Buenos Aires, Argentina.

Abstract

l-Serine is a nonessential 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). The Brucella abortus genome encodes two PGDHs (SerA-1 and SerA-2), involved in the first step in l-serine biosynthesis, and one PSAT and one PSP, responsible for the second and third steps, respectively. In this study, we demonstrate that the serA1 serA2 double mutant and the serC and serB single mutants are auxotrophic for l-serine. These auxotrophic mutants can be internalized but are unable to replicate in HeLa cells and in J774A.1 macrophage-like cells. Replication defects of auxotrophic mutants can be reverted by cell medium supplementation with l-serine at early times postinfection. In addition, the serB mutant is attenuated in the murine intraperitoneal infection model and has an altered lipid composition, since the 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.

KEYWORDS:

l-serine; Brucella; biosynthesis; virulence

PMID:
31740531
PMCID:
PMC6977118
[Available on 2020-07-22]
DOI:
10.1128/IAI.00840-19
[Indexed for MEDLINE]

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