Comparison of mutants of Toxoplasma gondii selected for resistance to azithromycin, spiramycin, or clindamycin - PubMed (original) (raw)

Comparative Study

Comparison of mutants of Toxoplasma gondii selected for resistance to azithromycin, spiramycin, or clindamycin

E R Pfefferkorn et al. Antimicrob Agents Chemother. 1994 Jan.

Abstract

Azithromycin and spiramycin markedly inhibited the growth of Toxoplasma gondii in cultured human fibroblasts. However, 3 days of treatment were required to reveal their full antitoxoplasma activity. This delayed onset of inhibition was similar to that previously reported for clindamycin. Mutants of T. gondii resistant to azithromycin (AziR-1) and spiramycin (SprR-1) were isolated and compared with a previously described mutant resistant to clindamycin (ClnR-2). Mutant ClnR-2 was cross-resistant to all three antibiotics, while AziR-1 was cross-resistant only to spiramycin and SprR-1 was cross-resistant only to azithromycin. In short-term studies of protein synthesis by freshly prepared extracellular parasites, clindamycin and azithromycin were effective only at concentrations much greater than their 50% inhibitory concentrations in infected cultures and the resistant mutants did not differ from the wild type in antibiotic sensitivity. Thus, protein synthesis on cytoplasmic ribosomes of the parasite did not seem to be the target of these antibiotics. To determine whether mitochondrial protein synthesis in T. gondii was inhibited by clindamycin or azithromycin, wild-type parasites were grown in cultured cells in the presence of antibiotic concentrations well above the 50% inhibitory concentrations. Mitochondrial function, measured by oxygen uptake per purified extracellular parasite, did not decrease substantially, after the parasites had multiplied 11-fold in the presence of antibiotic. Thus, mitochondrial protein synthesis did not seem to be the target of clindamycin or azithromycin. An alternative target is protein synthesis in the putative apicomplexan organelle that has a 35-kb genome.

PubMed Disclaimer

Similar articles

Cited by

References

    1. Antimicrob Agents Chemother. 1991 May;35(5):903-9 - PubMed
    1. Biochim Biophys Acta. 1984 Feb 24;781(1-2):100-11 - PubMed
    1. J Antimicrob Chemother. 1987 Nov;20 Suppl B:47-56 - PubMed
    1. Antimicrob Agents Chemother. 1974 Jun;5(6):647-51 - PubMed
    1. Nucleic Acids Res. 1984 Jun 11;12(11):4653-63 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources