Boromycin as a potential anti-toxoplasma and anti-cryptosporidium drug

Primary Author: Jaypee Abenoja

Faculty Sponsor: Roberta O’Connor

 

Primary College/Unit: College of Veterinary Medicine

Category: Medical and Life Sciences

Campus: Pullman

 

Abstract:

Toxoplasma gondii and Cryptosporidium parvum, members of the phylum Apicomplexa, are considered significant pathogens of both humans and animals worldwide. They are obligate intracellular parasites that cause serious conditions like neurological abnormalities, blindness and chronic diarrhea especially to immunocompromised individuals. Unfortunately, aside from significant toxicity on mammalian cells, current therapies against these parasites become ineffective through time because of drug resistance, making the discovery of new therapeutic drugs a priority. Here we described the activity of Boromycin (BM), a lipid-soluble antibiotic produced by Streptomyces antibioticus only known before as a drug for gram positive bacteria, against T. gondii and C. parvum.

BM’s in vitro activity against T. gondii and C. parvum was evaluated using various assays including proliferation inhibition, invasion assay and immunofluorescence to characterize the morphological changes of the parasites after being exposed to BM.

BM potently inhibits intracellular proliferation of T. gondii (EC50=2.13nM) and C. parvum (EC50=6.46nM) into their host cells. Irreversible inhibition on the ability of extracellular T. gondii to invade host cells was also observed after 2 hours of incubation with BM. Furthermore,

immunofluorescence of the parasites using anti-surface antigen glycoprotein-1 (SAG1) antibodies show detectable parasitophorous vacuoles (PV) but with randomly distributed surface antigens and complete loss of morphologically intact parasites within the vacuoles. We also determined after cytotoxicity assays that BM is very selective against parasites at the same time safe to mammalian host cells (Selectivity Index= of 3582.7). These promising results suggest BM as an exciting drug candidate for treating toxoplasmosis and cryptosporidiosis.