Serine hydroxymethyltransferase controls blood-meal digestion in the midgut of Aedes aegypti mosquitoes

Abstract

Background Female Aedes aegypti mosquitoes are vectors of arboviruses that cause diverse diseases of public health significance. Blood protein digestion by midgut proteases provides anautogenous mosquitoes with the nutrients essential for oocyte maturation and egg production. Midgut-specific miR-1174 affects the functions of the midgut through its target gene serine hydroxymethyltransferase (SHMT). However, less is known about SHMT-regulated processes in blood digestion by mosquitoes. Methods RNAi of SHMT was realized by injection of the double-stranded RNA at 16 h post-eclosion. The expression of SHMT at mRNA level and protein level was assayed by real-time PCR and Western blotting, respectively. Statistical analyses were performed with GraphPad7 using Student’s t-test. Results Here, we confirmed that digestion of blood was inhibited in SHMT RNAi-silenced female A. aegypti mosquitoes. Evidence is also presented that all SHMT-depleted female mosquitoes lost their flight ability and died within 48 h of a blood meal. Furthermore, most examined digestive enzymes responded differently in their transcriptional expression to RNAi depletion of SHMT, with some downregulated, some upregulated and some remaining stable. Phylogenetic analysis showed that transcriptional expression responses to SHMT silence were largely unrelated to the sequence similarity between these enzymes. Conclusions Overall, this research shows that SHMT was expressed at a low level in the midgut of Aedes aegypti mosquitoes, but blood-meal digestion was inhibited when SHMT was silenced. Transcriptional expressions of different digestive enzymes were affected in response to SHMT depletion, suggesting that SHMT is required for the blood-meal digestion in the midgut and targeting SHMT could provide an effective strategy for vector mosquito population control.

The Interplay Between Nutrition and the Dynamics of the Midgut Microbiome of the MosquitoAedes aegyptiReveals Putative Symbionts

“…These pathways have key enzymes for the digestion of blood, which is the case of the glycine and serine utilization pathway, detected in the microbiome of adult mosquitoes. The silencing of one of the pivotal enzymes in the latter pathway (serine transferase, SMHT) caused the formation of clots of non-digested blood in female mosquitoes’ midguts and a phenotype of ovarian underdevelopment (Li et al, 2019), corroborating with our results and strengthening the hypothesis of a nutritional symbiosis between Enterobacteria and A. aegypti .…”

Microbial exposure across life reduces susceptibility ofAedes aegyptito Zika virus by enhancing blood digestion and limiting midgut cell infection

“…Since blood digestion occurs in 2 phases where disparate enzymes dominate each phase (74), it is also possible that the digestive enzymes that have different efficiencies were differentially expressed across antibiotic treatments. We observed late trypsins and serine-type endopeptidases (enzyme types commonly found in the latter phase of digestion) (74–77) in all bloodfed antibiotic groups at 2 dpf; greater resolution of how digestion enzymes change over time is warranted to test this hypothesis. While over 300 serine protease-like proteins have been described in Aedes spp.…”

Molecular signature of domestication in the arboviral vectorAedes aegypti

“…aegypti , a phenomenon that has been also reported in Daphnia (79) and a few other organisms (82–85). By selecting from a rich stock of ancestral and weakly evolving standing variants from African populations, we observe that some of the “Aaa molecular signature” genes such as the odorant receptor gene AAEL000616 found within modules linked to active periods or sleep-like states (86), the chymotrypsin JHA15 (AAEL001703) found to be highly expressed before a blood meal (87), and the immune-related recognition gene AAEL019958 found to be exclusively expressed in ovaries of female mosquitoes (88), and several chemosensory genes have switched to directional selection in several out-of-Africa populations, where the fast emergence of novel adaptations can be easily promoted by the redundant organization of olfaction to cope with novel geographical and anthropogenic evolutionary pressures.…”