Toxoplasma gondii and Cryptosporidium parvum, members of the phylum Apicomplexa, are significant pathogens of both humans and animals worldwide for which new and effective therapeutics are needed. Here, we describe the activity of the antibiotic boromycin against Toxoplasma and Cryptosporidium Boromycin potently inhibited intracellular proliferation of both T. gondii and C. parvum at half-maximal effective concentrations (EC50) of 2.27 nM and 4.99 nM, respectively. Treatment of extracellular T. gondii tachyzoites with 25 nM boromycin for 30 min suppressed 84% of parasite growth, but T. gondii tachyzoite invasion into host cells was not affected by boromycin. Immunofluorescence of boromycin-treated T. gondii showed loss of morphologically intact parasites with randomly distributed surface antigens inside the parasitophorous vacuoles. Boromycin exhibited a high selectivity for the parasites over their host cells. These results suggest that boromycin is a promising new drug candidate for treating toxoplasmosis and cryptosporidiosis.
Apicomplexan parasites cause severe disease in both humans and their domesticated animals. Since these parasites readily develop drug resistance, development of new, effective drugs to treat infection caused by these parasites is an ongoing challenge for the medical and veterinary communities. We hypothesized that invertebrate-bacterial symbioses might be a rich source of anti-apicomplexan compounds because invertebrates are susceptible to infections with gregarines, parasites that are ancestral to all apicomplexans. We chose to explore the therapeutic potential of shipworm symbiotic bacteria as they are bona fide symbionts, are easily grown in axenic culture and have genomes rich in secondary metabolite loci [1,2]. Two strains of the shipworm symbiotic bacterium, Teredinibacter turnerae, were screened for activity against Toxoplasma gondii and one strain, T7901, exhibited activity against intracellular stages of the parasite. Bioassay-guided fractionation identified tartrolon E (trtE) as the source of the activity. TrtE has an EC50 of 3 nM against T. gondii, acts directly on the parasite itself and kills the parasites after two hours of treatment. TrtE exhibits nanomolar to picomolar level activity against Cryptosporidium, Plasmodium, Babesia, Theileria, and Sarcocystis; parasites representing all branches of the apicomplexan phylogenetic tree. The compound also proved effective against Cryptosporidium parvum infection in neonatal mice, indicating that trtE may be a potential lead compound for preclinical development. Identification of a promising new compound after such limited screening strongly encourages further mining of invertebrate symbionts for new anti-parasitic therapeutics.
The study determined the positivity rate of Trypanosoma evansi and Neospora caninum antibodies in water buffaloes in the province of Nueva Ecija, Philippines using Polymerase Chain Reaction (PCR) for T. evansi and competitive Enzyme-linked Immunosorbent Assay (cELISA) for N. caninum antibodies . A total of 100 whole blood and 100 serum samples were collected to test for T. evansi and N. caninum , respectively. Rotat 1.2 VSG gene was target using PCR for T. evansi detection. Neospora caninum antibody detection was done from the serum samples using cELISA test kit. Results revealed that the positivity rate of T. evansi in Nueva Ecija was 11% (11/100). The positive animals identified were from the municipalities of Muñoz (4/16; 25%), Sta. Rosa (3/13; 23.08%) and Talugtug (4/16; 25%). The seropositive rate of Nueva Ecija for N. caninum. was 46% (46/100), seropositive animals were identified in Cabanatuan City, 57.14% (4/7); Science City of Muñoz, 43.14% (22/51); Sta. Rosa, 40% (4/10); Sto. Sunday, 50% (6/12); and Talugtug 50% (10/20). The seropositivity rate of N. caninum and the presence of T. evansi in Nueva Ecija may contribute to the cases of abortions in the province and further studies should be employed to confirm the association of these organisms to abortion cases on water buffaloes.