Plasmodium falciparum gametocytes: still many secrets of a hidden life

Abstract

SummarySexual differentiation and parasite transmission are intimately linked in the life cycle of malaria parasites. The specialized cells providing this crucial link are the Plasmodium gametocytes. These are formed in the vertebrate host and are programmed to mature into gametes emerging from the erythrocytes in the midgut of a blood-feeding mosquito. The ensuing fusion into a zygote establishes parasite infection in the insect vector. Although key mechanisms of gametogenesis and fertilization are becoming progressively clear, the fundamental biology of gametocyte formation still presents open questions, some of which are specific to the human malaria parasite Plasmodium falciparum. Developmental commitment to sexual differentiation, regulation of stage-specific gene expression, the profound molecular and cellular changes accompanying gametocyte specialization, the requirement for tissue-specific sequestration in P. falciparum gametocytogenesis are proposed here as areas for future investigation. The epidemiological relevance of parasite transmission from humans to mosquito in the spread of malaria and of Plasmodium drug resistance genes indicates that understanding molecular mechanisms of gametocyte formation is highly relevant to design strategies able to interfere with the transmission of this disease. Plasmodium sexual differentiation: the pathway for transmission

ThePlasmodium falciparumblood stages acquire factor H family proteins to evade destruction by human complement

“…Because gametocytogenesis is induced in ABS parasites by stress factors like drug pressure or immune response molecules [reviewed in Talman et al (2004), Alano (2007) and Pradel (2007)], we further investigated if NHS represents a stress factor that induces gametocyte formation. ABSs at a starting parasitemia of 5% were cultivated in cell culture medium either supplemented with 10 vol% NHS or HIS over a period of 240 h. Medium was exchanged every 12 h to ensure the presence of active complement throughout the experiments.…”

Quantitative assessment of Plasmodium falciparum sexual development reveals potent transmission-blocking activity by methylene blue

“…These form under the insect midgut epithelium after exflagellation of male gametocytes to produce microgametes that fuse with female macrogametes and subsequent parasite traversal across the peritrophic matrix surrounding the blood meal (24). For the most frequently prescribed ACT (Coartem), which comprises lumefantrine plus an artemisinin derivative (25), we also examined exflagellation of stage V gametocytes as an indicator of maturity and infectivity (26).…”

DNA Repair Mechanisms and Their Biological Roles in the Malaria Parasite Plasmodium falciparum

“…Intraerythrocytic parasites can also adopt an alternative, sexual-stage developmental pathway, in which they form male or female gametocytes. Over a 2-week period, these stages mature and become infectious for mosquitoes (17). Upon transmission, gametocytes convert into gametes that can then mate to form a zygote (15).…”