The Plasmodium bottleneck: malaria parasite losses in the mosquito vector

Nearly one million people are killed every year by the malaria parasite Plasmodium. Although the disease-causing forms of the parasite exist only in the human blood, mosquitoes of the genus Anopheles are the obligate vector for transmission. Here, we review the parasite life cycle in the vector and highlight the human and mosquito contributions that limit malaria parasite development in the mosquito host. We address parasite killing in its mosquito host and bottlenecks in parasite numbers that might guide intervention strategies to prevent transmission.

Surface-expressed enolases of Plasmodium and other pathogens

Enolase is the eighth enzyme in the glycolytic pathway, a reaction that generates ATP from phosphoenol pyruvate in cytosolic compartments. Enolase is essential, especially for organisms devoid of the Krebs cycle that depend solely on glycolysis for energy. Interestingly, enolase appears to serve a separate function in some organisms, in that it is also exported to the cell surface via a poorly understood mechanism. In these organisms, surface enolase assists in the invasion of their host cells by binding plasminogen, an abundant plasma protease precursor. Binding is mediated by the interaction between a lysine motif of enolase with Kringle domains of plasminogen. The bound plasminogen is then cleaved by specific proteases to generate active plasmin. Plasmin is a potent serine protease that is thought to function in the degradation of the extracellular matrix surrounding the targeted host cell, thereby facilitating pathogen invasion. Recent work revealed that the malaria parasite Plasmodium also expresses surface enolase, and that this feature may be essential for completion of its life cycle. The therapeutic potential of targeting surface enolases of pathogens is discussed.

Transgenic mosquitoes for malaria control: progresses and challenges / Mosquitos transgênicos para o controle da malária: progressos e desafios

Malaria kills millions of people every year and the current strategies to control the disease, such as insecticides and drugs have not been completely efficient. Because of that, novel means to fight against malaria are of utmost importance. Advances in the study of the mosquito vector and its interactions with the malaria parasite made scientists think that it is possible to genetically manipulate the mosquitoes to make them inefficient vectors. Here we review the advances on the introduction of foreign genes into the mosquito germ line, the characterization of tissue-specific promoters, the identification of gene products that block development of the parasite in the mosquito, and we discuss the recent generation of transgenic mosquitoes impaired for malaria transmission. While much progress has been made, many years of research are still needed before transgenic mosquitoes can be used in the field.

A malária mata milhões de pessoas a cada ano e as estratégias atuais de controle da doença, como inseticidas e drogas não têm sido tão eficientes. Por este motivo, novos meios para o combate à malária são de extrema importância. Avanços no estudo do mosquito vetor e sua interação com o parasito da malária fizeram os cientistas pensarem que é possível a manipulação genética dos mosquitos para torná-los vetores ineficientes. Neste artigo, revisamos os avanços na introdução de genes exógenos na linhagem germinativa de mosquitos, a caracterização de promotores específicos de certos tecidos, a identificação de produtos gênicos que bloqueiam o parasita no mosquito, bem como discutimos a recente geração de mosquitos transgênicos, menos eficientes na transmissão de malária. Enquanto muitos progressos foram obtidos, muitos anos de pesquisa são ainda necessários para que mosquitos transgênicos possam ser utilizados na natureza.

Interrupting malaria transmission by genetic manipulation of anopheline mosquitoes.

Malaria ranks among the deadliest infectious diseases that kills more than one million persons every year. The mosquito is an obligatory vector for malaria transmission. In the mosquito, Plasmodium undergoes a complex series of developmental events that includes transformation into several distinct morphological forms and the crossing of two different epithelia--midgut and salivary gland. Circumstantial evidence suggests that crossing of the epithelia requires specific interactions between Plasmodium and epithelial surface molecules. By use of a phage display library we have identified a small peptide-SM1--that binds to the surfaces of the mosquito midgut and salivary glands. Transgenic Anopheles stephensi mosquitoes expressing a SM1 tetramer from a blood-inducible and gut-specific promoter are substantially impaired in their ability to sustain parasite development and transmission. A second effector gene, phospholipase A2, also impairs parasite transmission in transgenic mosquitoes. These findings have important implications for the development of new strategies for malaria control.