Inability of Pneumocystis organisms to incorporate bromodeoxyuridine suggests the absence of a salvage pathway for thymidine.
Because thymidine metabolism is a potential target for therapy of Pneumocystis pneumonia, it was investigated whether Pneumocystis organisms have a salvage pathway for thymidine by administering 5-bromo-2'-deoxyuridine (BrdU) to mice and rats with Pneumocystis pneumonia. Although BrdU incorporation was detected in host cells, no incorporation was seen in Pneumocystis organisms infecting either rats or mice. This suggests that Pneumocystis organisms do not have a salvage pathway for thymidine, and that inhibitors of de novo synthesis, such as thymidylate synthase inhibitors, may be effective drugs for treating Pneumocystis pneumonia.
Vestereng
Vibeke H
VH
Critical Care Medicine Department, Clinical Center, National Institutes of Health, Building 10, Room 7D43, MSC 1662, Bethesda, MD 20892-1662, USA.
Kovacs
Joseph A
JA
Critical Care Medicine Department, Clinical Center, National Institutes of Health, Building 10, Room 7D43, MSC 1662, Bethesda, MD 20892-1662, USA.
D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism*; D007421:Intestine, Small / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D011010:Pneumocystis / Q000378:metabolism*; D011020:Pneumonia, Pneumocystis / Q000382:microbiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013936:Thymidine / Q000378:metabolism
D001973:Bromodeoxyuridine; D013936:Thymidine