Citrulline is converted to arginine on day 5 of eCM restoring plasma arginine levels to uninfected levels.

Mice were injected i.v. with PbA on day 0 PI. A-C: On day 5PI (just prior to eCM on day 6PI), mice were injected ip with equimolar citrulline or arginine (430 mM) at time 0 and then plasma from n = 3 mice was obtained at the selected timepoints. The plasma levels of (A) arginine, (B) citrulline, and (C) ornithine were measured by HPLC. Uninfected mice (n = 3) were control group. The experiment was repeated. Citrulline; Arginine. D: Mice were injected twice daily from day 1 PI with citrulline or saline (vehicle); uninfected, untreated mice were used as controls. On day 6PI, plasma was collected, and arginase activity was measure using the arginase activity assay (Millipore-Sigma, St-Louis,MO). pE, F: Groups (n = 3) of mice were injected with D2-labeled citrulline and the levels of arginine and citrulline assessed by mass spectrometry at the selected timepoints. (E) D2-Citrulline; D2-Arginine; (F) Citrulline; Arginine.