ABSTRACT
The protein synthesis inhibitors (PSIs) represent a large, structurally diverse and clinically indispensable group of antibacterial agents (Gale et al., 1981; Kucers and Bennett, 1987). In the chemotherapy of protozoan parasites, however, PSIs have found considerably less use. There are only two, relatively uncommon parasitic infections for which PSIs are the drugs of choice: tetracycline for balantidiasis and clindamycin (plus quinine) for babesiosis (Abramowicz, 1986). Three additional PSIs are recommended as alternative agents: paromomycin, emetine (or its derivative dehydroemetine) and spiramycin. This limited development of antiprotozoal PSIs is in part due to the assumption that the protein synthesis machinery of parasite and host are largely similar, precluding selective toxicity. Recently, however, ribosomal RNA (rRNA) sequence analysis has revealed the protozoa to be a highly diverse group of organisms (Sogin et al., 1989). Studies in our laboratory have focussed on the intestinal parasite Giardia lamblia; its rRNA is, overall, no more closely related to mammalian rRNA than is bacterial rRNA (Edlind, 1989a; Sogin et al., 1989). Thus, the potential for selective antiprotozoal toxicity appears to exist. Furthermore, recent clinical studies have rekindled an interest in the antiparasitic potential of PSIs. These studies include:
1. the use of tetracycline or doxycycline in chloroquine-resistant malaria (Krogstad et al., 1988; Pang et al., 1988);
2. the promising activities of spiramycin and clindamycin against Cryptosporidium infection in AIDS paitents (Portnoy et al., 1984; Moskovitz et al., 1988); and
3. the treatment of cutaneous leishmaniasis with tropical paromomycin (El-On et al., 1988) or tetracycline derivatives (Khairulin et al., 1989).
