Hypervirulent knockout

Most studies of parasite virulence have focused on identifying genes whose loss causes decreased virulence or infectivity. In the April 13 Science, Cunningham et al. report the characterization of two genes in the protozoan parasite Leishmania, mutation of which causes hypervirulence (Science 2001, 292:285-287). Stephen Beverley and colleagues at Washington University demonstrate that Leishmania mutants lacking the genes for pteridine reductase 1 (PTR1) or biopterin transporter BT1 exhibit increased virulence, lesion formation and parasite burden when inoculated into mice. The ptr1^- and bt1^- lines had lower levels of tetrahydrobiopterin (H4B) which caused increased metacyclogenesis, differentiation to the infective form. Hence, genes regulating pteridine metabolism have evolved to control parasite differentiation and virulence.