Improved efficacy of tetracycline by acaciasides on Dirofilaria immitis

Abstract

The discovery of Wolbachia, a bacterial endosymbiont that occurs in the filarial parasite and its sensitivity to tetracycline, has fostered a new initiative in the development of suitable antifilarial drugs. The present study is an attempt to investigate whether adding acaciasides (saponins from Acacia auriculiformis) to the standard dose of tetracycline would further improve the efficacy of tetracycline treatment against Dirofilaria immitis microfilariae in vivo. Treatment of microfilaremic adult dogs (body weight range 8-12 kg) with tetracycline at 10 mg/kg/day for 40 days resulted in 72% and 83% reduction in mf count on days 15 and 30, respectively, and the maximum reduction in mf count (91%) was achieved on day 75 post-treatment. However, treatment with tetracycline (10 mg/kg/day for 40 days) followed by acaciasides (10 mg/kg/day for 7 days) resulted in almost 100% clearance of mf at a faster rate on day 45 post-treatment and ensured long-term (until 4 months post-treatment) protection against microfilaremia. Data from polymerase chain reaction analysis reveals that compared to untreated dogs, in treated dogs, there was marked reduction in Wolbachia specific wsp markers in fast depleting mf population. The present data indicate that prior tetracycline treatment enhances microfilaricidal activity of saponins. This effect may be additive or synergistic as the worms are weakened by Wolbachia depletion, and these weakened microfilariae are possibly killed by the saponins.

Human and Animal Dirofilariasis: the Emergence of a Zoonotic Mosaic

“…In BALB/c mice infected with Litomosoides sigmodontis and treated with rifampin alone or with doxycycline for 14 days, the elimination of Wolbachia from worms and the inhibition of development and embryogenesis were shown, and few worms survived after treatment (446). Microfilaricide and adulticide activity (163) and the total elimination of microfilariae for at least 4 months were found when tetracycline treatment was followed by the administration of acaciasides (Acacia auriculiformis-derived saponins) (104). The effects of antibiotic treatment on D. immitis-infected dogs have also been studied.…”

In vitro activity and in vivo efficacy of the saponin diosgenyl 2-amino-2-deoxy-β-d-glucopyranoside hydrochloride (HSM1) alone and in combination with daptomycin and vancomycin against Gram-positive cocci

“…Saponins form complexes with sterols and cause sterol-dependent membrane permeabilization. The antimicrobial activity of saponins is generally attributed to these membranepermeabilizing properties (Datta et al, 2009;Yang et al, 2006). Studies have demonstrated that membrane impermeability plays an important role in resistance to antibiotics.…”

“…The mechanism by which such a combination achieves synergy is believed to be by facilitating the entry of the antimicrobial compounds into cells after the partial disruption of the cell membrane through its action. Moreover, it is possible that the positive interaction is a result of a combined effect of increased access to the intracellular target for vancomycin or daptomycin and the secondary effects of the saponins themselves (Datta et al, 2009;Sung & Lee, 2008).…”