In vitro drug susceptibility of two strains of the wildlife trypanosome, Trypanosoma copemani : A comparison with Trypanosoma cruzi

Abstract

Trypanosomes are blood protozoan parasites that are capable of producing illness in the vertebrate host. Within Australia, several native Trypanosoma species have been described infecting wildlife. However, only Trypanosoma copemani has been associated with pathological lesions in wildlife hosts and more recently has been associated with the drastic decline of the critically endangered woylie (Bettongia penicillata). The impact that some trypanosomes have on the health of the vertebrate host has led to the development of numerous drug compounds that could inhibit the growth or kill the parasite. This study investigated and compared the in vitro susceptibility of two strains of T. copemani (G1 and G2) and one strain of Trypanosoma cruzi (10R26) against drugs that are known to show trypanocidal activity (benznidazole, posaconazole, miltefosine and melarsoprol) and against four lead compounds, two fenarimols and two pyridine derivatives (EPL-BS1937, EPL-BS2391, EPL-BS0967, and EPL-BS1246), that have been developed primarily against T.cruzi. The in vitro cytotoxicity of all drugs against L6 rat myoblast cells was also assessed. Results showed that both strains of T. copemani were more susceptible to all drugs and lead compounds than T. cruzi, with all IC50 values in the low and sub-μM range for both species. Melarsoprol and miltefosine exhibited the highest drug activity against both T. copemani and T. cruzi, but they also showed the highest toxicity in L6 cells. Interestingly, both fenarimol and pyridine derivative compounds were more active against T. copemani and T. cruzi than the reference drugs benznidazole and posaconazole. T. copemani strains exhibited differences in susceptibility to all drugs demonstrating once again considerable differences in their biological behaviour.

Repurposing of terconazole as an anti Trypanosoma cruzi agent

“…Terconazole was first described in the 1980s as a highly-active antifungal in dermatophytosis and candidiasis topical treatments and also possesses a moderate oral broad-spectrum activity tested in guinea pigs, rats, mice and turkeys (Van Cutsem et al., 1983). Here we demonstrate that terconazole has trypanocidal activity in epimastigotes from different DTUs and also in the clinically relevant life-stages of T. cruzi , trypomastigotes and amastigotes, with IC 50 values similar to those calculated for other azoles such as posaconazole (IC 50 : 5.4 μM) (Botero et al., 2017). Furthermore, in this study we show that terconazole is more potent against trypomastigotes and amastigotes than the reference drug benznidazole not only according to the IC 50 values obtained in this work but also to those previously reported by other authors (Moreno et al., 2010).…”

The kinetoplast DNA of the Australian trypanosome, Trypanosoma copemani, shares features with Trypanosoma cruzi and Trypanosoma lewisi

“…Trypanosoma copemani G1 and G2 have previously been shown to 490 exhibit considerable differences in their biological behaviour such 491 as growth requirements, susceptibility to drugs, and capability to 492 infect cells in vitro (Botero et al, 2016a(Botero et al, , 2017. Furthermore, T.…”

Benznidazole induces in vitro anaerobic metabolism in Trypanosoma cruzi epimastigotes

“…cruzi exposed to various concentrations of anti-parasitic drugs such as benzinidazole, nifurtimox and miltefosine [18]. Also Moreno et al [19] have shown the in vitro susceptibility and resistance of different T. cruzi strains to benzinidazole.…”