Tectorigenin reduces type IV pilus-dependent cell adherence in Clostridium perfringens.

Clostridium perfringens is an anaerobic, Gram-positive bacterium that causes a range of diseases in humans and animals around the globe. The type IV pilus (TFP) system plays a key role in the colonization and invasion of host cells, biofilm formation and gliding motility, which is vital for C. perfringens infection. Therefore, targeting TFP function may be a promising strategy for the treatment of C. perfringens infection. Here, we investigated the potential inhibitory effects of tectorigenin (TE), an isoflavone extracted from the rhizome of the Chinese herb Belamcanda chinensis (L.) DC, on gliding motility, biofilm formation, adherence to cells and antibacterial activity of C. perfringens. Tectorigenin significantly inhibited gliding motility, biofilm formation and adherence to Caco-2 cells without observable antibacterial activity against C. perfringens. In addition, we also demonstrated that the inhibitory effect of TE on TFP function appears to be partially achieved by the suppression of TFP-associated genes. These findings demonstrate that TE may have the potential to be developed as a new anti-virulence drug for C. perfringens infection, particularly for the targeting of TFP.

Screening for potential prophylactics targeting sporozoite motility through the skin.

BACKGROUND: Anti-malarial compounds have not yet been identified that target the first obligatory step of infection in humans: the migration of Plasmodium sporozoites in the host dermis. This movement is essential to find and invade a blood vessel in order to be passively transported to the liver. Here, an imaging screening pipeline was established to screen for compounds capable of inhibiting extracellular sporozoites. METHODS: Sporozoites expressing the green fluorescent protein were isolated from infected Anopheles mosquitoes, incubated with compounds from two libraries (MMV Malaria Box and a FDA-approved library) and imaged. Effects on in vitro motility or morphology were scored. In vivo efficacy of a candidate drug was investigated by treating mice ears with a gel prior to infectious mosquito bites. Motility was analysed by in vivo imaging and the progress of infection was monitored by daily blood smears. RESULTS: Several compounds had a pronounced effect on in vitro sporozoite gliding or morphology. Notably, monensin sodium potently affected sporozoite movement while gramicidin S resulted in rounding up of sporozoites. However, pre-treatment of mice with a topical gel containing gramicidin did not reduce sporozoite motility and infection. CONCLUSIONS: This approach shows that it is possible to screen libraries for inhibitors of sporozoite motility and highlighted the paucity of compounds in currently available libraries that inhibit this initial step of a malaria infection. Screening of diverse libraries is suggested to identify more compounds that could serve as leads in developing 'skin-based' malaria prophylactics. Further, strategies need to be developed that will allow compounds to effectively penetrate the dermis and thereby prevent exit of sporozoites from the skin.