Lacerda, M. V. G. | Search bioRxiv

bioRxiv2022

The genome of the brackish-water malaria vector Anopheles aquasalis

Anopheles aquasalis is a primary malaria vector in coastal South America that grows in brackish waters of mangroves. Its importance has increased in recent years as it has been established as a model for parasite-vector studies for non-model Plasmodium species, such as P. yoelli. In this study, we present the complete genome of An. aquasalis and offer some insights into evolution and physiology. With a 162Mb and 12,446 coding proteins, the An. aquasalis genome is similar in size and gene content as other neotropical anophelines. 1,038 single-copy orthologs are present in An. aquasalis and all Diptera and it was possible to infer that An. aquasalis diverged from An. darlingi (the main malaria vector in inland South America) nearly 14 million years ago (mya). Ion transport and metabolism proteins is one the major gene families in An. aquasalis with 660 genes. Amongst these genes, important gene families relevant for osmosis control (e.g., aquaporins, vacuolar-ATPases, Na+/K+-ATPases and carbonic anhydrases) were identified in one-to-one orthologs with other anophelines. Evolutionary analysis suggests that all osmotic regulation genes are under strong purifying selection. We also observed low copy number variation in immunity-related genes (for which all classical pathways were described) and insecticide resistance genes. This is the third genome of a neotropical anopheline published so far. The data provided by this study may offer candidate genes for further studies on parasite-vector interactions and for studies on how brackish water anophelines deals with high fluctuation in water salinity. Significance StatementThe brackish water mosquito Anopheles aquasalis is a primary malaria vector in coastal South America. Besides its peculiar ecological features (it is one of the few anopheline mosquitoes that survives high fluctuation of water salinity), An. aquasalis has gained relevance in recent years as a model for parasite-vector studies for non-model Plasmodium parasites. Still, the physiology and genetics of An. aquasalis are poorly understood. Here we present the genome of An. aquasalis with more than 12,000 annotated genes, offering insights in genome evolution, osmoregulation related, immunity, chemosensory and insecticide resistance genes. The data presented here will help to further advance the studies on An. aquasalis genetics and physiology to better understand parasite-vector interactions in non-model organisms.

genomics↗

bioRxiv2019

Platelet disturbances correlate with endothelial cell activation in uncomplicated Plasmodium vivax malaria

IntroductionPlatelets drive endothelial cell activation in many diseases. However, if this occurs in Plasmodium vivax malaria is unclear. As platelets have been reported to be activated and to play a role in inflammatory response during malaria, we hypothesized that this would correlate with endothelial alterations during acute illness.\n\nMethodsWe performed platelet flow cytometry of PAC-1 and P-selectin. We measured Platelet markers (CXCL4, CD40L, P-selectin, Thrombopoietin, IL-11) and endothelial markers (ICAM-1, von Willebrand Factor and E-selectin) in plasma with a multiplex-based assay. The values of each mediator were used to generate heatmaps, K-means clustering and Principal Component analysis. In addition, we determined pair-wise Pearsons correlation coefficients to generate correlation networks.\n\nResultsPlatelet counts were reduced, and mean platelet volume increased in malaria patients. The activation of circulating platelets in flow cytometry did not differ between patients and controls. CD40L levels (Median [IQ]: 517 [406-651] vs. 1029 [732- 1267] pg/mL, P=0.0001) were significantly higher in patients, while P-selectin (Median [IQ]: 17.0 [15.4-20.6] vs. 22.2 [17.6-25.7] ng/mL, P=0.0621) and CXCL4 showed a nonsignificant trend towards higher levels in patients. The network correlation approach demonstrated the correlation between markers of platelet and endothelial activation, and the heatmaps revealed a distinct pattern of activation in two subsets of P. vivax patients when compared to controls.\n\nConclusionplatelet activation occurs in uncomplicated vivax malaria and this correlates with higher endothelial cell activation, especially in a subset of patients.\n\nAUTHOR SUMMARYEndothelial cell activation is a key process in the pathogenesis of Plasmodium vivax malaria. Platelets are classically involved endothelial cell activation in several diseases, but their role in context of vivax malaria remains unclear. Thrombocytopenia is the most common hematological disturbance in P. vivax-infected patients, and platelets have been implicated in parasitemia control. In this study, we studied the activation of platelets in association with endothelial cell activation in vivax malaria. Platelets retrieved from infected peripheral blood were non-activated when analyzed by flow cytometry; however, they displayed higher mean volume and significantly reduced counts. We also found higher levels of circulating factors associated with platelet activation (especially CD40L), thrombopoiesis and endothelial cell activation in infected patients. Further, through pair-wise correlation and clustering analysis, we found a subgroup of patients showing significant associations between markers of platelet and endothelial activation in a pattern different from that of endemic controls. Collectively, our findings point to a peculiar role of platelets in endothelial cell activation in vivax malaria and indicate a heterogeneous host response in the setting of uncomplicated disease, a finding to be further explored in future studies.

immunology↗