Isocitrate lyase (AceA) is required for Salmonella persistence but not for acute lethal infection in mice

Abstract

Isocitrate lyase is required for fatty acid utilization via the glyoxylate shunt. Although isocitrate lyase is essential for Salmonella persistence during chronic infection, it is dispensable for acute lethal infection in mice. Substrate availability in the phagosome appears to evolve over time, with increasing fatty acid dependence during chronic infection.

FIG. 1.

Isocitrate lyase (AceA) is not required for acute lethal infection in mice. (Top) Survival of C3H/HeN mice infected intraperitoneally with 10³ CFU of wild-type S. enterica serovar Typhimurium 14028s or an isogenic aceA mutant strain. An attenuated aroA mutant CL1509 was included as a control. (Bottom) Survival of C3H/HeN mice infected orally with 10⁷, 10⁸, or 10⁹ CFU of wild-type S. enterica serovar Typhimurium 14028s or an isogenic aceA mutant strain. Murine challenge experiments were each performed twice with essentially identical results (five per group).

FIG. 2.

Salmonella splenic organ burden following intraperitoneal inoculation of mice. Splenic CFU were quantified in mice euthanized at selected intervals following intraperitoneal inoculation of C3H/HeN mice with 10³ CFU of wild-type S. enterica serovar Typhimurium 14028s or an isogenic aceA mutant strain (six per group).

FIG. 3.

Isocitrate lyase (AceA) is required for Salmonella persistence in MLN following oral inoculation of 129Sv mice. MLN CFU were quantified in 129 Sv mice euthanized at selected time intervals following oral inoculation with 10⁹ CFU containing a mixture of equivalent quantities of aroA mutant S. enterica serovar Typhimurium CL1509 and an isogenic aceA aroA mutant derivative. This experiment was performed twice with virtually identical results (six per group).