Antimicrosporidial activity of (fluoro)quinolones in vitro and in vivo

Abstract

Abstract. Microsporidia are a cause of emerging and opportunistic infections in humans and animals. Although two drugs are currently being used to treat microsporidiosis, concerns exist that albendazole is only selective for inhibiting some species of microsporidia that infect mammals, and fumagillin appears to have been found to be toxic. During a limited sequence survey of the Vittaforma corneae (syn. Nosema corneum Shadduck, Meccoli, Davis et Font, 1990) genome, a partial gene encoding for the ParC topoisomerase IV subunit was identified. The purpose of this set of studies was to determine if fluoroquinolones, which target topoisomerase IV, exert activity against Encephalitozoon intestinalis (syn. Septata intestinalis Cali, Kotler et Orenstein, 1993) and V. corneae in vitro, and whether these compounds could prolong survival of V. corneae-infected athymic mice. Fifteen fluoroquinolones were tested. Of these, norfloxacin and ofloxacin inhibited E. intestinalis replication by more than 70% compared with non-treated control cultures, while gatifloxacin, lomefloxacin, moxifloxacin, and nalidixic acid (sodium salt) inhibited both E. intestinalis and V. corneae by at least 60% at concentrations not toxic to the host cells. These drugs were tested in vivo also, where gatifloxacin, lomefloxacin, norfloxacin, and ofloxacin prolonged survival of V. corneae-infected athymic mice (P < 0.05), whereas moxifloxacin and nalidixic acid failed to prolong survival. Therefore, these results support continued studies for evaluating the efficacy of the fluoroquinolones for treating microsporidiosis and for characterizing the target(s) of these fluoroquinolones in the microsporidia.

Animal cell cultures in microsporidial research: their general roles and their specific use for fish microsporidia

“…This approach was used to screen a variety of drugs for their therapeutic potential and to identify albendazole and fumagilin as effective at inhibiting the growth of E. cuniculi in vitro but at the same time causing little harm to the human cells, which in this case were MRC5 (Beauvis et al 1994). Similar systems have been used to evaluate the antimicrosporidial activity of other classes of compounds, including fluoroquinolones (Didier et al 2005; Didier et al 2006). Although animals ultimately will have to be used to test the efficacy of therapeutics, the advantage of the in vitro approach is in providing preliminary screens of effectiveness rapidly and inexpensively.…”

Parasitic diarrheal disease: drug development and targets

“…and E. bieneusi in vitro (Bacchi and Weiss, 2004 ). The antimicrosporidial activity of various fluoroquinolones derivatives such as norfloxacin ( 4 ) and ofloxacin ( 5 ) is more than gatifloxacin ( 6 ), lomefloxacin ( 7 ), moxifloxacin ( 8 ), and nalidixic acid ( 9 ) and can be the effective option of chemotherapy (Didier et al, 2005 ). It was observed that TNP-470 ( 10 ), ovalicin ( 11 ) and its derivatives inhibited E. intestinalis replication by more than 70% in vitro which indicates that these compounds can be used as medication for this infection (Didier et al, 2006 ).…”

Antiviral, antifungal, and antiparasitic activities of fluoroquinolones optimized for treatment of bacterial infections: a puzzling paradox or a logical consequence of their mode of action?

“…In addition, nalidixic acid, norfloxacin, ofloxacin, moxifloxacin, gatifloxacin, lomefloxacin, and some more fluoroquinolones inhibited growth of the microsporidia Encephalitozoon intestinalis and Vittaforma corneae to 50 % at concentrations ranging from 0.9 to 98.4 μM [112]. Furthermore, ciprofloxacin caused a 50 % growth inhibition of Babesia microti, B. bigemina, B. caballi, B. equi, and B. bovis at concentrations of 2.5 to 15.8 μM [113].…”

“…Nalidixic acid and several fluoroquinolones like ciprofloxacin, norfloxacin, enoxacin, ofloxacin, fleroxacin, clinafloxacin, pefloxacin, and sparfloxacin exerted an antitrypanosomal in vitro and in vivo effect at micromolar concentrations [38,[106][107][108][109][110][111][112][113][114][115][116].…”