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Nwankwo, I.

Publications and source records attributed to Nwankwo, I..

2 recordsLinked to original sources

Inheritance of the genome-less apicoplast in the 'apicoplast-minus' Plasmodium falciparum

Most apicomplexan parasites contain a plastid-derived organelle called the apicoplast, which originated through secondary endosymbiosis. As a result of this evolutionary trajectory, the non-photosynthetic apicoplast is surrounded by four membranes and contains many bacterial-like, druggable targets. It is widely accepted that asexual malaria parasites (Plasmodium falciparum) can thrive under antibiotic treatment if supplemented with high concentrations of isopentenyl pyrophosphate (IPP, 200 {micro}M) and these IPP-rescued parasites are thought to lack the apicoplast and its 35 kb genome but possess many vesicles. However, our findings challenge this apicoplast-minus concept. In late-stage schizonts, we observed that the apicoplast-derived vesicles nearly colocalize with mitochondria and are properly distributed into merozoites during schizogony, suggesting that they are inherited rather than newly synthesized in each asexual cycle. Further, immuno-electron microscopy (immuno-EM) revealed that the "apicoplast-minus" parasites possess structures surrounded by four membranes, in addition to single-membrane-surrounded entities. The presence of four-membrane-bound structures suggests that the apicoplast has not truly disappeared in the "apicoplast-minus" P. falciparum but remains in a distinct, diminished form. We termed this genome-less apicoplast derivative the apicosome, drawing an analogy to the genome-less mitochondrial derivative known as the mitosome. We propose that apicosomes retain essential biochemical and/or structural functions, which act as barriers to the complete loss of apicoplast when the parasites face antibiotic stress and IPP rescue.

microbiology↗

Maintenance of pyrophosphate homeostasis in multiple subcellular compartmentsis essential in Plasmodium falciparum

Pyrophosphate is a byproduct of numerous cellular reactions that use ATP or other nucleoside triphosphates to synthesize DNA, RNA, protein, and other molecules. Its degradation into monophosphate is thus crucial for the survival and proliferation of all life forms. The human malaria parasite Plasmodium falciparum encodes two classes of pyrophosphatases to hydrolyze pyrophosphate. The first consists of P. falciparum proton pumping vacuolar pyrophosphatases (PfVP1 and PfVP2), which localize to the parasites subcellular membranes and work as proton pumps. The second includes P. falciparum soluble pyrophosphatases (PfsPPases), which have not been well characterized. Interestingly, the gene locus of PfsPPase encodes two isoforms, PfsPPase1 (PF3D7_0316300.1) and PfsPPase2 (PF3D7_0316300.2). PfsPPase2 contains a 51- amino acid organellar localization peptide that is absent in PfsPPase1. Here, we combine reverse genetics and biochemical approaches to identify the localization of PfsPPase1 and PfsPPase2 and elucidate their individual functions. We show that PfsPPases are essential for the asexual blood stage. While PfsPPase1 solely localizes to the cytoplasm, PfsPPase2 exhibits multiple localizations including the mitochondrion, the apicoplast, and, to a lesser extent, the cytoplasm. Our data suggest that P. falciparum has taken a unique evolutionary trajectory in pyrophosphate metabolism by utilizing a leader sequence to direct sPPases to the mitochondrion and apicoplast. This differs from model eukaryotes as they generally encode multiple sPPases at distinct genetic loci to facilitate pyrophosphate degradation in cytosolic and organellar compartments. Our study highlights PfsPPases as promising targets for the development of novel antimalarial drugs.

microbiology↗