Search

The emerging spread of drug-resistant malaria parasites highlights the need for new antimalarial agents. This study evaluated the growth-inhibitory effects of sparsomycin (Sm), a peptidyl transferase inhibitor, against Plasmodium falciparum 3D7 (chloroquine-sensitive strain), P. falciparum K1 (resistant to multiple drugs, including chloroquine), P. yoelii 17XNL (cause of uncomplicated rodent malaria) and P. berghei ANKA (cause of complicated rodent malaria). Using a fluorescence-based assay, we found that Sm exhibited half-maximal inhibitory concentrations (IC 50 ) of 12.07 and 25.43 nM against P. falciparum 3D7 and K1, respectively. In vitro treatment of P. falciparum 3D7 with Sm at 10 or 50 nM induced morphological alteration, blocked parasites in the ring state and prevented erythrocyte reinvasion, even after removal of the compound. In mice infected with P. yoelii 17XNL, the administration of 100 μg/kg Sm for 7 days did not affect parasitemia. Meanwhile, treatment with 300 μg/kg Sm resulted in a significantly lower parasitemia peak (18.85%) than that observed in the control group (40.13%). In mice infected with P. berghei ANKA, both four and seven doses of Sm (300 μg/kg) prolonged survival by 33.33%. Our results indicate that Sm has potential antiplasmodial activities in vitro and in vivo, warranting its further development as an alternative treatment for malaria.

Objectives: Sparsomycin, which exhibits rare broad-spectrum antibiotic and antitumour activity against bacteria, Archaea, Eucarya and various cancer cell lines, has been widely used as a powerful tool to study protein synthesis. Here we report the draft genome sequence of Streptomyces sparsogenes ATCC 25498 from the American Type Culture Collection (ATCC), which has become an organism of interest owing to its ability to produce sparsomycin., Methods: The whole-genome sequence of S. sparsogenes ATCC 25498 was determined using a high-throughput Illumina HiSeq 2000 platform and genome assembly was performed using the SOAPdenovo method., Results: Whole-genome sequencing analysis revealed a genome size of 10.0Mb. A total of 41 secondary metabolite biosynthetic gene clusters were identified. The gene cluster for the biosynthesis of sparsomycin was localised on scaffold 9., Conclusions: The genome sequence of S. sparsogenes ATCC 25498 will not only aid in understanding the regulatory mechanism of sparsomycin biosynthesis but will also reveal the ability of the isolate to produce novel bioactive secondary metabolites., (Copyright © 2017 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.)

We determined the sites at which ribosomes form initiation complexes on Rous sarcoma virus RNA in order to determine how initiation of Pr76gag synthesis at the fourth AUG codon from the 5' end of Rous sarcoma virus strain SR-A RNA occurs. Ribosomes bind almost exclusively at the 5'-proximal AUG codon when chloride is present as the major anion added to the translational system. However, when chloride is replaced with acetate, ribosomes bind at the two 5'-proximal AUG codons, as well as at the initiation site for Pr76gag. We confirmed that the 5'-proximal AUG codon is part of a functional initiation site by identifying the seven-amino acid peptide encoded there. Our results suggest that (i) translation in vitro of Rous sarcoma virus virion RNA results in the synthesis of at least two polypeptides; (ii) the pattern of ribosome binding observed for Rous sarcoma virus RNA can be accounted for by the modified scanning hypothesis; and (iii) the interaction between 40S ribosomal subunits or 80S ribosomal complexes is stronger at the 5'-proximal AUG codon than at sites farther downstream, including the initiation site for the major viral proteins.