Selective transport of a new class of purine antimetabolites by the protozoan parasite Trypanosoma brucei.

Purine antimetabolites have been very successful therapeutic agents against a host of infectious diseases and malignancies. Success of the treatment relies as much on the efficient accumulation by the target cell or organism as it does on selective action on a vital biochemical pathway of the target cell. Here we compare the ability of a new class of tricyclic purine antimetabolites to interact with transporters from human erythrocytes or Trypanosoma brucei. We show that these compounds display a remarkable selectivity for the parasite's transporters. The adenine analogue showed greater trypanocidal activity than the hypoxanthine or guanine analogues in vitro.

Molecular analysis of Salmonella enterica serotype Dublin: building bridges between population genetic and molecular epidemiological studies.

Population genetic studies of Salmonella enterica serotype Dublin using multilocus enzyme electrophoresis have recognised two dominant clones termed Du1 and Du3. The characterisation of plasmids in Dublin suggests greater strain diversity. The application of restriction enzyme fragmentation pattern (REFP) analysis of genomic DNA using Sau3A and HincII together with plasmid subtractive analysis can resolve anomalies in earlier comparisons. Twenty-six isolates were selected for inclusion in the study. All had been previously characterised with respect to their plasmids, and were isolated from the USA, Canada and five European countries. On the basis of plasmid profiles, 17 were predicted to correspond with Du1 and Du3. Sau3A digestion generated two distinct REFPs (A and B) of < 70% similarity, which corresponded with Du1 and Du3. After the contribution of plasmid-derived bands was subtracted, two variants of A (A1 and A2) and four of B (B1, B2, B3 and B4) were recognised. Seventeen were concordant with predictions from population genetic studies. Nine that could not be predicted on the basis of atypical plasmid profiles all showed REFP A1 (Du1) and were consistent with the incursion of additional plasmids or plasmid cointegration. REFPs from HincII digests generally corroborated Sau3A data but showed greater overall similarity between the strains and more influence from plasmid DNA.