Publications

Cardiolipin (CL) is a phospholipid localized to the mitochondria, and its biosynthesis is essential for mitochondrial structure and function. We report here the identification and characterization of a cDNA encoding the first mammalian cardiolipin synthase (CLS1) in humans and mice. This cDNA exhibits sequence homology with members of a CLS gene family that share similar domain structure and chemical properties. Expression of the human CLS (hCLS1) cDNA in reticulocyte lysates or insect cells led to a marked increase in CLS activity. The enzyme is specific for CL synthesis, because no significant increase in phosphatidylglycerol phosphate synthase activity was observed. In addition, CL pool size was increased in hCLS1-overexpressing cells compared with controls. Furthermore, the hCLS1 gene was highly expressed in tissues such as heart, skeletal muscle, and liver, which have been shown to have high CLS activities. These results demonstrate that hCLS1 encodes an enzyme that synthesizes CL.

Malaria infections in Africa frequently include multiple parasite strains. We examined the relationship between the number of infecting Plasmodium falciparum strains and the responses to 3 different combination therapies in 3072 patients with uncomplicated malaria at 7 sites in Uganda. Patients infected with > or =3 strains had almost 3 times the odds of treatment failure (odds ratio, 2.93 [95% confidence interval, 2.51-3.43]; P<.001), compared with those infected with 1 or 2 strains. Our data suggest that efforts to reduce the complexity of infection in highly endemic areas through the use of intermittent presumptive therapy, improved case management, and reduction in transmission intensity may improve the efficacy of antimalarial therapies.