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pyrE  (STM3733) encodes orotate phosphoribosyltransferase (OPRTase; EC 2.4.2.10), the fifth enzyme of the  de novo  pyrimidine biosynthetic pathway. We identified a  ΔpyrE  mutant as under selection in screening of a  Salmonella  mutant library in 4-day old chicks. Here, we confirm that a  ΔpyrE  mutant colonizes 4-day old chicks poorly in competitive infection with isogenic wild type, and that the ability of this mutant to colonize chicks could be restored by providing a copy of  pyrE in trans . We further show that our  ΔpyrE  mutant grows poorly in nutrient poor conditions  in vitro , and that the ability of this mutant to grow is restored, both  in vitro  and in chicks, when precursors to the pyrimidine salvage pathway were provided. This finding suggests that the environment in the chick intestine during our infections lacks sufficient precursors of the pyrimidine salvage pathway to support  Salmonella  growth. Finally, we show that the colonization defect of a  ΔpyrE  mutant during infection occurs in to chicks, but not in CBA/J mice or ligated ileal loops in calves. Our data suggest that  de novo  pyrimidine synthesis is necessary for colonization of  Salmonella  Typhimurium in the chick, and that the salvage pathway is not used in this niche.

De novo pyrimidine synthesis is necessary for intestinal colonization of Salmonella Typhimurium in chicks