Apicomplexan parasites, such as Toxoplasma gondii, Plasmodium spp., Babesia spp., and Cryptosporidium spp., cause significant morbidity and mortality. Existing treatments are problematic due to toxicity and the emergence of drug-resistant parasites. Because protozoan tubulin can be selectively disrupted by small molecules to inhibit parasite growth, we assembled an in vitro testing cascade to fully delineate effects of candidate tubulin-targeting drugs on Toxoplasma gondii and vertebrate host cells. Using this analysis, we evaluated clemastine, an antihistamine that has been previously shown to inhibit Plasmodium growth by competitively binding to the CCT/TRiC tubulin chaperone as a proof-of-concept. We concurrently analyzed astemizole, a distinct antihistamine that blocks heme detoxification in Plasmodium. Both drugs have EC50 values of ~2 µM and do not demonstrate cytotoxicity or vertebrate microtubule disruption at this concentration. Parasite subpellicular microtubules are shortened by treatment with either clemastine or astemizole but not after treatment with pyrimethamine, indicating that this effect is not a general response to antiparasitic drugs. Immunoblot quantification indicates that the total α-tubulin concentration of 0.02 pg/tachyzoite does not change with clemastine treatment. In conclusion, the testing cascade allows profiling of small-molecule effects on both parasite and vertebrate cell viability and microtubule integrity.
High community diversity may either prevent or promote the establishment of exotic species. The biotic resistance hypothesis holds that species-rich communities are more resistant to invasion than species-poor communities due to mechanisms including greater interspecific competition. Conversely, the invasional meltdown hypothesis proposes that greater exotic diversity increases invasibility via facilitative interactions between exotic species. To evaluate the degree to which biotic resistance or invasional meltdown influences marine community structure during the assembly period, we studied the development of marine epibenthic “fouling” communities at two southern California harbors. With a focus on sessile epibenthic species, we found that fewer exotic species established as total and exotic richness increased during community assembly and that this effect remained after accounting for space availability. We also found that changes in exotic abundance decreased over time. Throughout the assembly period, gains in exotic abundance were greatest when space was abundant and richness was low. Altogether, we found greater support for biotic resistance than invasional meltdown, suggesting that both native and exotic species contribute to biotic resistance during early development of these communities. However, our results indicate that biotic resistance may not always reduce the eventual dominance of exotic species.
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