ABSTRACT
Many classes of drugs have been tested against infections caused by Pneumocystis since the early part of the twentieth century, when the organism was first shown to cause disease. The two most effective therapies identified empirically were the antifolates sulfamethoxazole-trimethoprim in fixed combination and the antiprotozoal diamidine pentamidine. The principal of selective toxicity requires that drugs be targeted to block required processes in pathogenic organisms and that the targeted process be different enough so that the host is unharmed while growth of the pathogenic organism is prevented or the organism is even destroyed. Thus, improvement over these empirically selected agents requires robust biochemical support both to isolate the drug target and to evaluate inhibition of the target in the intact organism. Pneumocystis does not easily lend itself to biochemical study, but in the last few years methods for isolating purified and biochemically active organisms have improved [1-9]. These methods, coupled with the powerful methods of recombinant DNA technology, have facilitated studies directly on drug targets in the organism [10-12].
