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.
We show that the intraerythrocytic stages of the malaria parasite Plasmodium falciparum bind plasminogen and mediate its conversion into plasmin to inactivate parasite‐bound C3b. This complement ...evasion mechanism counteracts terminal complex formation and hence promotes parasite survival in human blood.
Metarhizium anisopliae infects mosquitoes through the cuticle and proliferates in the hemolymph. To allow M. anisopliae to combat malaria in mosquitoes with advanced malaria infections, we produced ...recombinant strains expressing molecules that target sporozoites as they travel through the hemolymph to the salivary glands. Eleven days after a Plasmodium-infected blood meal, mosquitoes were treated with M. anisopliae expressing salivary gland and midgut peptide 1 (SM1), which blocks attachment of sporozoites to salivary glands; a single-chain antibody that agglutinates sporozoites; or scorpine, which is an antimicrobial toxin. These reduced sporozoite counts by 71%, 85%, and 90%, respectively. M. anisopliae expressing scorpine and an SM1₈:scorpine fusion protein reduced sporozoite counts by 98%, suggesting that Metarhizium-mediated inhibition of Plasmodium development could be a powerful weapon for combating malaria.
Despite the critical role of
sporozoites in malaria transmission, we still know little about the mechanisms underlying their development in mosquitoes. Here, we use single-cell RNA sequencing to ...characterize the gene expression profiles of 16,038
sporozoites isolated throughout their development from midgut oocysts to salivary glands, and from forced salivation experiments. Our results reveal a succession of tightly regulated changes in gene expression occurring during the maturation of sporozoites and highlight candidate genes that could play important roles in oocyst egress, sporozoite motility, and the mechanisms underlying the invasion of mosquito salivary glands and mammalian hepatocytes. In addition, the single-cell data reveal extensive transcriptional heterogeneity among parasites isolated from the same anatomical site, suggesting that
development in mosquitoes is asynchronous and regulated by intrinsic as well as environmental factors. Finally, our analyses show a decrease in transcriptional activity preceding the translational repression observed in mature sporozoites and associated with their quiescent state in salivary glands, followed by a rapid reactivation of the transcriptional machinery immediately upon salivation.
mating is initiated by the swarming of males at dusk followed by females flying into the swarm. Here, we show that mosquito swarming and mating are coordinately guided by clock genes, light, and ...temperature. Transcriptome analysis shows up-regulation of the clock genes
(
) and
(
) in the head of field-caught swarming
males. Knockdown of
and
expression affects
and
male mating in the laboratory, and it reduces male
swarming and mating under semifield conditions. Light and temperature affect mosquito mating, possibly by modulating
and/or
expression. Moreover, the desaturase gene
is up-regulated and rhythmically expressed in the heads of swarming males and regulates the production of cuticular hydrocarbons, including heptacosane, which stimulates mating activity.
The malaria development in the mosquito midgut is a complex process that results in considerable parasite losses. The mosquito gut microbiota influences the outcome of pathogen infection in ...mosquitoes, but the underlying mechanisms through which gut symbiotic bacteria affect vector competence remain elusive. Here, we identified two
strains (Y1 and J1) isolated from field-caught female
from China and assessed their effect on
development in
. Colonization of
midgut by
Y1 significantly renders the mosquito resistant to
infection, while
J1 has no impact on parasite development. Parasite inhibition by
Y1 is induced by the activation of the mosquito immune system. Genome-wide transcriptomic analysis by RNA-seq shows a similar pattern of midgut gene expression in response to
Y1 and J1 in sugar-fed mosquitoes. However, 24 h after blood ingestion
Y1 modulates more midgut genes than
J1 including the c-type lectins (CTLs), CLIP serine proteases and other immune effectors. Furthermore, silencing of several
Y1-induced anti-
factors like the thioester-containing protein 1 (TEP1), fibrinogen immunolectin 9 (FBN9) or leucine-rich repeat protein LRRD7 can rescue parasite oocyst development in the presence of
Y1, suggesting that these factors modulate the
Y1-mediated anti-
effect. This study enhances our understanding of how gut bacteria influence mosquito-
interactions.
The Pimienta Formation (J-Pi) of the Tampico Misantla Basin (TMB) in Mexico is known for its potential as unconventional onshore hydrocarbon reserves. The area of interest in this study is located in ...the western-central part of the TMB, where no significant production has been established from unconventional resources. Given the low permeability and low porosity characteristics of the carbonaceous mudstone in the Pimienta formation, it is necessary to implement techniques to increase the area of flow from the reservoir to the borehole, achieving profitable oil and gas extraction.
The geomechanical properties of rock strata are essential inputs for the design and implementation of shale oil and gas production engineering, such as horizontal drilling and hydraulic fracturing. Understanding the capabilities of the rock to yield and contain hydraulic fractures is essential to designing safe and efficient well stimulations. Likewise, the wellbore stability is of critical importance to the successful development of secondary and tertiary recovery systems.
In this study, core samples from the Pimienta Formation in the TMB are analyzed through undrained multi-stage triaxial tests, emphasizing the estimated in-situ geo stresses and the effect of the mineral composition of the rock. The geomechanical parameters of compressional strength, Poisson ratio (PR), and Young's modulus of the Pimienta formation are obtained from the analysis of the experimental data and finding correlations to the mineral composition of the samples. A detailed characterization is completed under the conventional rock mechanics methodologies of Mohr-Coulomb and Hoek-Brown failure criterion, as well as Brittleness Index (BI).
•Undrained Multi-stage Triaxial Tests in prominent Pimienta formation in the Tampico-Misantla Basin, Mexico.•Detailed characterization is completed under the established rock mechanics methodologies.•Area of Interest is classified as prospective unconventional land resources.
fertilization, an essential step for the development of the malaria parasite in the mosquito, is a prime target for blocking pathogen transmission. Using phage peptide display screening, we ...identified MG1, a peptide that binds to male gametes and inhibits fertilization, presumably by competing with a female gamete ligand. Anti-MG1 antibodies bind to the female gamete surface and, by doing so, also inhibit fertilization. We determined that this antibody recognizes HSP90 on the surface of
female gametes. Our findings establish
HSP90 as a prime target for the development of a transmission-blocking vaccine.IMPORTANCEMalaria kills over half a million people every year and this number has not decreased in recent years. The development of new tools to combat this disease is urgently needed. In this article, we report the identification of a key molecule-HSP90-on the surface of the parasite's female gamete that is required for fertilization to occur and for the completion of the parasite cycle in the mosquito. HSP90 is a promising candidate for the development of a transmission-blocking vaccine.
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