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Howick, V.

Publications and source records attributed to Howick, V..

3 recordsLinked to original sources

Single-cell transcriptional landscapes of Aedes aegypti midgut and fat body after a bloodmeal

Aedes aegypti mosquitoes are vectors for numerous arboviruses that have an increasingly substantial global health burden. Following a bloodmeal, mosquitoes experience significant physiological changes, primarily orchestrated by the midgut and fat body tissues. These changes begin with digestion and culminate in egg production. However, our understanding of those key processes at the cellular and molecular level remains limited. We have created a comprehensive cell atlas of the mosquito midgut and fat body by employing single-cell RNA sequencing and metabolomics techniques. This atlas unveils the dynamic cellular composition and metabolic adaptations that occur following a bloodmeal. Our analyses reveal highly diverse cell populations, specialized in digestion, metabolism, immunity, and reproduction. While the midgut primarily comprises enterocytes, enteroendocrine and intestinal stem cells, the fat body consists not only of trophocytes and oenocytes, but also harbors a substantial hemocyte population and a newly found fat body-yolk cell population. The fat body exhibits a complex cellular and metabolomic profile and exerts a central role in coordinating immune and metabolic processes. Additionally, an insect-specific virus, PCLV (Phasi Charoen-Like Virus) was detected in single cells, mainly in the midgut a week after the bloodmeal. These findings highlight the complexity of the mosquitos abdominal tissues, and pave the way towards the development of exquisitely refined vector control strategies consisting of genetically targeting specific cell populations and metabolic pathways necessary for egg development after a bloodmeal.

cell biology↗

A single-cell atlas of Plasmodium falciparum transmission through the mosquito

Malaria parasites have a complex life cycle featuring diverse developmental strategies, each uniquely adapted to navigate specific host environments. Here we use single-cell transcriptomics to illuminate gene usage across the transmission cycle of the most virulent agent of human malaria - Plasmodium falciparum. We reveal developmental trajectories associated with the colonisation of the mosquito midgut and salivary glands and elucidate the transcriptional signatures of each transmissible stage. Additionally, we identify both conserved and nonconserved gene usage between human and rodent parasites, which point to both essential mechanisms in malaria transmission and species-specific adaptations potentially linked to host tropism. Together, the data presented here, which are made freely available via an interactive website, establish the most complete atlas of the P. falciparum transcriptional journey to date. One sentence summarySingle-cell transcriptomics of P. falciparum transmission stages highlights developmental trajectories and gene usage.

genomics↗

Artemisinin-resistant malaria parasites show enhanced transmission to mosquitoes under drug pressure

Resistance to artemisinin combination therapy (ACT) in the Plasmodium falciparum parasite is threatening to reverse recent gains in reducing global deaths from malaria. Whilst resistance manifests as delayed asexual parasite clearance in patients following ACT treatment, the phenotype can only spread geographically via the sexual cycle and subsequent transmission through the mosquito. Artemisinin and its derivatives (such as dihydroartemisinin, DHA) as well as killing the asexual parasite form are known to sterilize male, sexual-stage gametes from activation. Whether resistant parasites overcome this artemisinin-dependent sterilizing effect has not, however, been fully tested. Here, we analysed five P. falciparum clinical isolates from the Greater Mekong Subregion, each of which demonstrated delayed clinical clearance and carried known resistance-associated polymorphisms in the Kelch13 gene (PfK13var). As well as demonstrating reduced sensitivity to artemisinin-derivates in in vitro asexual growth assays, certain PfK13var isolates also demonstrated a marked reduction in sensitivity to these drugs in an in vitro male gamete activation assay compared to a sensitive control. Importantly, the same reduction in sensitivity to DHA was observed when the most resistant isolate was assayed by standard membrane feeding assays using Anopheles stephensi mosquitoes. These results indicate that ACT use can favour resistant over sensitive parasite transmission. A selective advantage for resistant parasite transmission could also favour acquisition of further polymorphisms, such as mosquito host-specificity or antimalarial partner-drug resistance in mixed infections. Favoured transmission of resistance under ACT coverage could have profound implications for the spread of multidrug resistant malaria beyond Southeast Asia. ONE SENTENCE SUMMARYArtemisinin-resistant clinical isolates can also demonstrate resistance to the transmission-blocking effects of artemisinin-based drugs, favouring resistance transmission to the mosquito.

microbiology↗