Ultrastructural morphology of Pneumocystis carinii exposed to (β-1-3 glucan synthase inhibitors LY 302146 and LY 307853

Abstract

Pneumocystis carinii (PC) is an extracellular pathogen which frequently causes pneumonia in immunocompromised patients and is a significant cause of morbidity and mortality in patients with acquired immunodeficiency syndrome (AIDS). Trimethoprim plus sulphamethoxazole and pentamidine are the most often prescribed treatments for PC induced pneumonia but these drugs often cause severe side-effects in individuals with AIDS and are less effective if relapse occurs. For these reasons the search for more effective compounds continues.The cell walls of PC cysts are rich in glucosyl/mannosyl/and N-acetyl-D-glucosamine residues and are digested by treatment with Zymolyase a β-1-3 glucanase. Therefore, compounds which are inhibitors of β-1-3 glucan synthase may be effective against PC. Immunosupressed mice infected with PC have been treated sucessfully with compounds LY302146 and LY307853 sodium salt both of which are inhibitors of β-1-3 glucan synthase. To help delineate their mode of action, electron microscopic evaluation of samples of PC grown in cultures containing these compounds was undertaken.