The development of malaria parasites in the mosquito midgut

Abstract

SummaryThe mosquito midgut stages of malaria parasites are crucial for establishing an infection in the insect vector and to thus ensure further spread of the pathogen. Parasite development in the midgut starts with the activation of the intraerythrocytic gametocytes immediately after take‐up and ends with traversal of the midgut epithelium by the invasive ookinetes less than 24 h later. During this time period, the plasmodia undergo two processes of stage conversion, from gametocytes to gametes and from zygotes to ookinetes, both accompanied by dramatic morphological changes. Further, gamete formation requires parasite egress from the enveloping erythrocytes, rendering them vulnerable to the aggressive factors of the insect gut, like components of the human blood meal. The mosquito midgut stages of malaria parasites are unprecedented objects to study a variety of cell biological aspects, including signal perception, cell conversion, parasite/host co‐adaptation and immune evasion. This review highlights recent insights into the molecules involved in gametocyte activation and gamete formation as well as in zygote‐to‐ookinete conversion and ookinete midgut exit; it further discusses factors that can harm the extracellular midgut stages as well as the measures of the parasites to protect themselves from any damage.

The s48/45 six-cysteine proteins: mediators of interaction throughout the Plasmodium life cycle

“…When stage V gametocytes are ingested by a mosquito taking a blood meal, they activate in the midgut and emerge from the erythrocyte; males exflagellate forming microgametes and fertilize female gametes to produce zygotes which then transform into motile ookinetes (Fig. 1A) (reviewed in Kuehn and Pradel (2010);Bennink et al (2016). During traversal through the midgut epithelial cells, ookinetes activate the mosquito immune response through the JNK pathway and some are “tagged” for complement lysis and perish as they come into contact with the hemolymph (Han and Barillas-Mury, 2002; Garver et al, 2013).…”

Plasmodium P47 : a key gene for malaria transmission by mosquito vectors

“…Plasmodium undergoes obligatory sexual reproduction and multiple developmental stages in the mosquito [5–7]. Mosquitoes become infected when a female ingests a blood meal containing Plasmodium gametocytes (Fig 1).…”

Phospholipases during membrane dynamics in malaria parasites

“…Inhibition of PI-PLC with the commercial PLC inhibitor U73122 prevents calcium-mediated signaling and thus activation of the plasmodial protein kinase B by calmodulin, in consequence impairing secretion of micronemal proteins (Raabe et al, 2011a(Raabe et al, , 2011bSingh et al, 2010;Vaid et al, 2008;Vaid and Sharma, 2006). The plasmodial PI-PLC is also involved in the signaling pathways initiating gametogenesis, as was shown for P. berghei and P. falciparum (reviewed in Bennink et al, 2016;Kuehn and Pradel, 2010). Once in the mosquito midgut, the intraerythrocytic gametocytes sense the change of hosts due to the perception of environmental factors present in the gut lumen, triggering their egress from the RBC and their transformation into gametes.…”

“…The high content of DAGs in gametocytes might be linked to the various signaling pathways that are activated to initiate gametogenesis, once the gametocytes have entered the mosquito midgut. Among others, during gametogenesis the second messengers DAG and inositol-(1,4,5)-triphosphate (IP 3 ) are produced by hydrolysis of phosphatidylinositol-(4,5)-biphosphate (PIP 2 ) through phospholipase C (PLC), leading to a release of calcium from the ER, which in turn activates calcium-dependent protein kinases of the parasite as described below (reviewed in Bennink et al, 2016;Kuehn and Pradel, 2010).…”

“…Following maturation, a process that takes 10 days for gametocytes of P. falciparum, the gametocytes are capable of forming gametes immediately after uptake by the blood-feeding Anopheles mosquito vector. The gametes fuse to form a motile zygote, termed ookinete, which traverses the gut wall of the mosquito and then transforms into an oocyst, in which the parasite undergoes another round of asexual replication before accumulating as infective sporozoites in the mosquito salivary glands (reviewed in Bennink et al, 2016;Kuehn and Pradel, 2010).…”