RESUMEN
Taxon-specific proteins are key determinants defining the biology of all organisms and represent prime drug targets in pathogens. However, lacking comparability with proteins in other lineages makes them particularly difficult to study. In malaria parasites, this is exacerbated by technical limitations. Here, we analyzed the cellular location, essentiality, function, and, in selected cases, interactome of all unknown non-secretory proteins encoded on an entire P. falciparum chromosome. The nucleus was the most common localization, indicating that it is a hotspot of parasite-specific biology. More in-depth functional studies with four proteins revealed essential roles in DNA replication and mitosis. The mitosis proteins defined a possible orphan complex and a highly diverged complex needed for spindle-kinetochore connection. Structure-function comparisons indicated that the taxon-specific proteins evolved by different mechanisms. This work demonstrates the feasibility of gene-by-gene screens to elucidate the biology of malaria parasites and reveal critical parasite-specific processes of interest as drug targets.
Asunto(s)
Malaria , Plasmodium falciparum , Humanos , Plasmodium falciparum/genética , Cromosomas Humanos Par 3 , Cinetocoros , MitosisRESUMEN
To evaluate protective antibody levels against hepatitis B surface antigen in HIV-infected and HIV-uninfected Kenyan children, this study enrolled 531 children. In the HIV-infected group, only 18.3% had protective hepatitis B surface antigen compared with 74.4% in the HIV-uninfected group (P < 0.0001). Perhaps HIV-infected children should be immunized differently.