Biology subjects

Elliott, K.

Publications and source records attributed to Elliott, K..

18 recordsLinked to original sources

bioRxiv2025

Nanogram of Arg 1 Delivered by extracellular vesicles restore ARG1 activity in a mouse model of ARG1-D and improve lifespan.

Arginase 1 (ARG1) deficiency (ARG1-D) is a rare genetic disorder due to loss of ARG1, the final enzyme in the urea cycle. ARG1-D hepatocytes are impaired in converting arginine into urea, resulting in elevated peripheral arginine and ammonia, which leads to progressive neurological symptoms. Current therapeutic strategies mainly focus on managing plasma arginine and ammonia level, but long-term outcomes remain poor. While no approved treatment specific for ARG1-D is available in the United States, a recombinant protein based enzyme replacement therapy is available in Europe. Recently, extracellular vesicles (EVs) are emerging as a powerful therapeutic vehicle. By using Capricors StealthX platform, EVs were engineered to express human ARG1 on their surface or encapsulated within. Regardless of its localization on the EV membrane, nanograms of ARG1 carried by EVs were biologically active and able to convert arginine into urea as potent as micrograms of human recombinant ARG1 (rHuArg1). Furthermore, ARG1- encapsulating EVs (STX-Arg1-in) were able to deliver ARG1 intracellularly but not EVs carrying ARG1 on their surface or rHuArg1. STX-Arg1-in EVs were further evaluated in a series of in vivo studies and results showed that STX-Arg1-in EVs were non-toxic and able to restore the arginase activities in the liver of the Arg1-/- mice, which leads to a lowered plasma arginine concentration similar to wildtype mice. Most importantly, Arg1-in expanded the life span of the lethal neonatal Arg1 deficiency mouse model. Taken together, our data suggested StealthX-engineered STX-Arg1-in EVs have a better safety profile due to extreme low dosage and had great potential as a novel enzyme replacement strategy for patients suffering from ARG1-D. Significance statementIntracellular delivery of recombinant protein and improved life span are endpoints of a successful enzyme replacement therapy for the treatment of ARG1-D. Using StealthX platform, a fully functional ARG1 enzyme was engineered to be carried inside of the extracellular vesicles, which allowed intracellular delivery of ARG1 protein in vitro and in vivo, with improvement of life span in a lethal neonatal mouse model of Arg1 deficiency. More importantly, no toxicity was observed, and efficacy was achieved with low dose, setting the base for an improved therapeutic approach.

genetics↗

bioRxiv2025

A Novel In Vitro Potency Assay Demonstrating the Anti-Fibrotic Mechanism of Action of CDCs in Deramiocel

Duchenne muscular dystrophy (DMD) is characterized by progressive skeletal and cardiac muscle degeneration driven by inflammation and fibrosis, ultimately leading to cardiomyopathy and premature death. Deramiocel, an allogeneic cell therapy composed of cardiosphere-derived cells (CDCs), has demonstrated potent anti-fibrotic and immunomodulatory effects in preclinical models and clinical trials, including HOPE-2 and its open-label extension (HOPE-2 OLE), where Deramiocel treatment significantly attenuated progression of skeletal and cardiac muscle dysfunction. Here, we describe the development of a novel in vitro potency assay to quantify the anti-fibrotic activity of Deramiocel. Conditioned media (CM) from multiple Deramiocel manufacturing lots significantly suppressed expression of collagen type I alpha 1 (COL1A1) and collagen type III alpha 1 (COL3A1) in primary human dermal fibroblasts compared with non-conditioned media controls, establishing a robust, reproducible readout of anti-fibrotic activity. The effect was dose-dependent and abrogated by sequential depletion of exosomes and soluble proteins, implicating both as critical mediators of Deramiocels mechanism of action. Importantly, CDCs in deramiocel lots classified as potent by this assay were shown to exert a clinically meaningful benefit in DMD patients in the HOPE-2 and HOPE-2 OLE studies. This assay represents a mechanistically informative, therapeutically relevant, reproducible, scalable, and regulatory-compliant approach for assessing Deramiocel potency, enabling consistent manufacturing and facilitating the continued development of Deramiocel as a disease-modifying therapy for DMD.

cell biology↗

bioRxiv2025

Using wingbeat frequency to estimate mass gained by seabirds

1. Energy intake is a fundamental currency in ecology that is critical to reproductive success, survival and lifetime fitness. Measuring foraging success in wild animals via biologgers has been a long-standing challenge. 2. Flying animals gain mass during foraging, and they must counteract the associated increased gravitational force by creating additional lift. Pennycuick (1996) proposed that wingbeat frequency (w) should vary with the square root of body mass [Formula], when other variables influencing wingbeat frequency are held constant. 3. We present a state-space model that estimates instantaneous changes in body mass by modelling this relationship with wingbeat frequency using animal-borne accelerometer and depth data. To demonstrate the usefulness of our proposed method, we applied it to biologging data from 55 thick-billed murres (Uria lomvia) during the incubation period. 4. Our mass estimates allowed us to identify areas associated with higher gains, and to demonstrate that foraging success was generally higher farther from the colony. However, 79% of foraging trips were associated with mass deficits. We performed simulation studies to assess the sensitivity of our method to parameter misspecification and the increase in accuracy gained from including the known mass at recapture. As estimates of energy intake allow for testing of long-standing hypotheses in foraging ecology, our method provides a new tool to help answer these questions with any animal that engages in flapping flight.

ecology↗

bioRxiv2024

A distinct circuit for biasing visual perceptual decisions and modulating superior colliculus activity through the mouse posterior striatum

The basal ganglia play a key role in visual perceptual decisions. Despite being the primary target in the basal ganglia for inputs from the visual cortex, the posterior striatums (PS) involvement in visual perceptual behavior remains unknown in rodents. We reveal that the PS direct pathway is largely segregated from the dorsomedial striatum (DMS) direct pathway, the other major striatal target for visual cortex. We investigated the role of the PS in visual perceptual decisions by optogenetically stimulating striatal medium spiny neurons in the direct pathway (D1-MSNs) of mice performing a visual change-detection task. PS D1-MSN activation robustly biased visual decisions in a manner dependent on visual context, timing, and reward expectation. We examined the effects of PS and DMS direct pathway activation on neuronal activity in the superior colliculus (SC), a major output target of the basal ganglia. Activation of either direct pathway rapidly modulated SC neurons, but mostly targeted different SC neurons and had opposite effects. These results demonstrate that the PS in rodents provides an important route for controlling visual decisions, in parallel with the better known DMS, and with distinct anatomical and functional properties. Significance StatementThe rodent posterior striatum (PS) is strongly innervated by visual cortex and thalamus, but its functional role in visual behavior has not been explored. We show that the PS initiates a direct pathway through the basal ganglia that is anatomically distinct from the more commonly studied dorsomedial striatum (DMS). Activating the PS direct pathway selectively biases decisions for expected, valued visual events. We also show that both DMS and PS direct pathways modulate neuronal activity in the superior colliculus, a structure critical for visual processing and sensorimotor function, and preferentially modulate collicular units with properties relevant in the visual detection task. These findings identify a distinct and novel circuit through the basal ganglia for controlling visually guided perceptual decisions.

neuroscience↗

bioRxiv2023

Multivalent Exosome based protein vaccine: a "mix and match" approach to epidemic viruses' challenges.

Endemic viruses are becoming increasingly the norm, and the development of a rapid and effective vaccine is emergent. Here, we used our StealthX exosome platform to express either Influenza H3 (Stealth X-Hemagglutinin, STX-H3) or SARS-CoV-2 Delta spike (Stealth X-Spike, STX-S) protein on the surface and facilitate their trafficking to the exosomes. When administered as single product, both STX-H3 and STX-S induced a strong immunization with the production of a potent humoral and cellular immune response in mice. Interestingly, these effects were obtained with administration of nanograms of protein and without adjuvant. Therefore, we tested the possibility of a multivalent vaccine: STX-H3 and STX-S exosomes were formulated together in a "mix and match" approach and the immune response was further evaluated. We showed that our STX-H3+S cocktail vaccine is as effective as the single components administered separately, resulting in a strong antibody and T-cell response. Our data show that our exosome platform has an enormous potential to revolutionize vaccinology by rapidly facilitating antigen presentation, and for therapeutics by enabling cell and tissue specific targeting.

immunology↗

bioRxiv2023

CRISPR/Cas9 generated MeSWEET10a mutants show reduced susceptibility to cassava bacterial blight and produce viable seed

Bacteria from the genus Xanthomonas are prolific phytopathogens that elicit disease in over 400 plant species. Xanthomonads carry a repertoire of specialized proteins called transcription activator-like (TAL) effectors that promote disease and pathogen virulence by inducing expression of host susceptibility (S) genes. Xanthomonas phaseoli pv. manihotis (Xpm) causes bacterial blight on the staple food crop, cassava. The Xpm effector, TAL20, induces ectopic expression of the S gene, MeSWEET10a, a sugar transporter that contributes to cassava bacterial blight susceptibility. We used CRISPR/Cas9 to generate multiple cassava lines with edits to the MeSWEET10a TAL20 effector binding site and/or coding sequence. In several of the regenerated lines, MeSWEET10a expression was no longer induced by Xpm and in these cases, we observed reduced cassava bacterial blight disease symptoms post Xpm infection. MeSWEET10a is expressed in cassava flowers. Therefore, we investigated flower development and reproductive function in an MeSWEET10a mutant line. We found that the MeSWEET10a mutant produced phenotypically wildtype cassava flowers and viable F1 seed. Thus, blocking MeSWEET10a induction is a viable strategy for decreasing cassava susceptibility to CBB.

plant biology↗

bioRxiv2023

Nanograms of SARS-CoV-2 Spike Protein Delivered by Exosomes Induce Potent Neutralization of Both Delta and Omicron Variants.

Exosomes are emerging as potent and safe delivery carriers for use in vaccinology and therapeutics. A better vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is needed to provide improved, broader, longer lasting neutralization of SARS-CoV-2, a more robust T cell response, enable widespread global usage, and further enhance the safety profile of vaccines given the likelihood of repeated booster vaccinations. Here, we use Capricors StealthX platform to engineer exosomes to express native SARS-CoV-2 spike Delta variant (STX-S) protein on the surface for the delivery of a protein-based vaccine for immunization against SARS-CoV-2 infection. The STX-S vaccine induced a strong immunization with the production of a potent humoral immune response as demonstrated by high levels of neutralizing antibody not only against the delta SARS-CoV-2 virus but also two Omicron variants (BA.1 and BA.5), providing broader protection than current mRNA vaccines. Additionally, both CD4+ and CD8+ T cell responses were increased significantly after treatment. Quantification of spike protein by ELISA showed that only nanograms of protein were needed to induce a potent immune response. This is a significantly lower dose than traditional recombinant protein vaccines with no adjuvant required, which makes the StealthX exosome platform ideal for the development of multivalent vaccines with a better safety profile. Importantly, our exosome platform allows novel proteins, or variants in the case of SARS-CoV-2, to be engineered onto the surface of exosomes in a matter of weeks, comparable with mRNA vaccine technology, but without the cold storage requirements. The ability to utilize exosomes for cellular delivery of proteins, as demonstrated by STX-S, has enormous potential to revolutionize vaccinology by rapidly facilitating antigen presentation at an extremely low dose resulting in a potent, broad antibody response.

immunology↗

bioRxiv2023

Exosome based multivalent vaccine: achieving potent immunization, broaden reactivity and T cell response with nanograms of proteins without any adjuvant.

Current approved vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have focused solely on the spike protein to provide immunity. The first vaccines were developed rapidly using spike mRNA delivered by lipid nanoparticles but required ultra-low storage and have had limited immunity against variations in spike. Subsequently, protein-based vaccines were developed which offer broader immunity but require significant time for development and use of an adjuvant to boost immune response. Here, exosomes were used to deliver a bi-valent protein-based vaccine, in which two independent viral proteins were used. Exosomes were engineered to express either SARS-CoV-2 Delta spike (Stealth X-Spike, STX-S) or the more conserved nucleocapsid (Stealth X-Nucleocapsid, STX-N) protein on the surface. When administered as single product (STX-S or STX-N) or in combination (STX-S+N), both STX-S and STX-N induced a strong immunization with the production of a potent humoral and cellular immune response. Interestingly, these results were obtained with administration of only nanograms of protein and without adjuvant. In two independent animal models (mouse and rabbit), administration of nanograms of the STX-S+N vaccine resulted in increased antibody production, potent neutralizing antibodies with cross-reactivity to other variants of spike and strong T-cell responses. Importantly, no competition in immune response was observed, allowing for delivery of nucleocapsid with spike to offer improved SARS-CoV-2 immunity. These data show that the StealthXTM exosome platform has an enormous potential to revolutionize vaccinology by combining the advantages of mRNA and recombinant protein vaccines into a superior, rapidly generated, low dose vaccine resulting in potent, broader immunity.

immunology↗

bioRxiv2022

A comparison of ImageJ and machine learning based image analysis methods to measure cassava bacterial blight disease severity

BackgroundMethods to accurately quantify disease severity are fundamental to plant pathogen interaction studies. Commonly used methods include visual scoring of disease symptoms, tracking pathogen growth in planta over time, and various assays that detect plant defense responses. Several image-based methods for phenotyping of plant disease symptoms have also been developed. Each of these methods has different advantages and limitations which should be carefully considered when choosing an approach and interpreting the results. ResultsIn this paper, we developed two image analysis methods and tested their ability to quantify different aspects of disease lesions in the cassava-Xanthomonas pathosystem. The first method uses ImageJ, an open-source platform widely used in the biological sciences. The second method is a few-shot support vector machine learning tool that uses a classifier file trained with five representative infected leaf images for lesion recognition. Cassava leaves were syringe infiltrated with wildtype Xanthomonas, a Xanthomonas mutant with decreased virulence, and mock treatments. Digital images of infected leaves were captured overtime using a Raspberry Pi camera. The image analysis methods were analyzed and compared for the ability to segment the lesion from the background and accurately capture and measure differences between the treatment types. ConclusionsBoth image analysis methods presented in this paper allow for accurate segmentation of disease lesions from the non-infected plant. Specifically, at 4-, 6-, and 9-days post inoculation (DPI), both methods provided quantitative differences in disease symptoms between different treatment types. Thus, either method could be applied to extract information about disease severity. Strengths and weaknesses of each approach are discussed.

plant biology↗

bioRxiv2022

A clinically annotated post-mortem approach to study multi-organ somatic mutational clonality in histologically healthy tissues.

Recent research on histologically healthy human tissues identified omnipresent mutational microclones, driven by somatic mutations known to be responsible for carcinogenesis (e.g., in TP53 or NOTCH1). These new insights are fundamentally changing current tumour evolution models, with broad oncological implications. Most studies are based on surgical remnant tissues, which are not available for many organs and rarely in a pan-organ setting (multiple organs from the same individual). Here, we describe an approach based on clinically annotated post-mortem tissues, derived from whole-body donors that are routinely used for educational purposes at human anatomy units. We validated this post-mortem approach using UV-exposed and unexposed epidermal skin tissues and confirm the presence of positively selected NOTCH1/2-, TP53- and FAT1-driven clones. No selection signals were detected in a set of immune genes or housekeeping genes. Additionally, we provide the first evidence for smoking-induced clonal changes in oral epithelia, likely underlying the origin of head and neck carcinogenesis. In conclusion, the whole-body donor-based approach provides a nearly unlimited healthy tissue resource to study mutational clonality and gain fundamental mutagenic insights in the presumed earliest stages of tumour evolution.

genomics↗

bioRxiv2022

Improving disease resistance in plants by editing the epigenome

Pathogens rely on expression of host susceptibility (S) genes to promote infection and disease. As DNA methylation is an epigenetic modification that affects gene expression, blocking access to S genes through targeted methylation could increase disease resistance. Xanthomonas phaseoli pv. manihotis, the causal agent of cassava bacterial blight (CBB), uses transcription activator-like20 (TAL20) to induce expression of the S gene MeSWEET10a. In this work, we direct methylation to the TAL20 effector binding element within the MeSWEET10a promoter using a synthetic zinc-finger DNA binding domain fused to a component of the RNA-directed DNA methylation pathway. We demonstrate that this methylation prevents TAL20 binding, blocks transcriptional activation of MeSWEET10a in vivo and that these plants display decreased CBB symptoms while maintaining normal growth and development. This work therefore presents an epigenome editing approach useful for crop improvement.

plant biology↗

bioRxiv2020

A new Spirodela polyrhiza genome and proteome reveal a conserved chromosomal structure with high abundances of proteins favoring energy production

Duckweeds are a monophyletic group of rapidly reproducing aquatic monocots in the Lemnaceae family. Spirodela polyrhiza, the Greater Duckweed, has the largest body plan yet the smallest genome size in the family (1C = 150 Mb). Given their clonal, exponentially fast reproduction, a key question is whether genome structure is conserved across the species in the absence of meiotic recombination. We generated a highly contiguous, chromosome-scale assembly of Spirodela polyrhiza line Sp7498 using Oxford Nanopore plus Hi-C scaffolding (Sp7498_HiC) which is highly syntenic with a related line (Sp9509). Both the Sp7498_HiC and Sp9509 genome assemblies reveal large chromosomal misorientations in a recent PacBio assembly of Sp7498, highlighting the necessity of orthogonal long-range scaffolding techniques like Hi-C and BioNano optical mapping. Shotgun proteomics of Sp7498 verified the expression of [~]2,250 proteins and revealed a high abundance of proteins involved in photosynthesis and carbohydrate metabolism among other functions. In addition, a strong increase in chloroplast proteins was observed that correlated to chloroplast density. This Sp7498_HiC genome was generated cheaply and quickly with a single Oxford Nanopore MinION flow cell and one Hi-C library in a classroom setting. Combining these data with a mass spectrometry-generated proteome illustrates the utility of duckweed as a model for genomics- and proteomics-based education.

plant biology↗

bioRxiv2019

Microsatellite instability as a tool to diagnose genome instability in CHO cell culture

As bioprocess intensification has increased over the last 30 years, yields from mammalian cell processes have increased from 10s of milligrams to over 10s of grams per liter. Most of these gains in productivity have been due to increasing cell numbers in the bioreactors, and with those increases in cell numbers, strategies have been developed to minimize metabolite waste accumulation, such as lactate and ammonia. Unfortunately, cell growth cannot occur without some waste metabolite accumulation, as central metabolism is required to produce the biopharmaceutical. Inevitably, metabolic waste accumulation leads to decline and termination of the culture. While it is understood that the accumulation of these unwanted compounds imparts a less than optimal culture environment, little is known about the genotoxic properties and the influence of these compounds on global genome instability. In this study, we examined the effects on Chinese hamster ovary (CHO) cells genome sequences and physiology due to exposure to elevated ammonia levels. We identified genome-wide de novo mutations, in addition to variants in functional regions of certain genes involved in the mismatch repair (MMR) pathway, such as DNA2, BRCA1 and RAD52, which led to loss-of-function and eventual genome instability. Additionally, we characterized the presence of microsatellites against the most recent Chinese Hamster genome assembly and discovered certain loci are not replicated faithfully in the presence of elevated ammonia, which represents microsatellite instability (MSI). Furthermore, we found 124 candidate loci that may be suitable biomarkers to gauge genome stability in CHO cultures.

genomics↗

bioRxiv2019

Metabolic Profiling of Aortic Stenosis and Hypertrophic Cardiomyopathy Identifies Mechanistic Contrasts in Substrate Utilisation

BackgroundAortic stenosis (AS) and hypertrophic cardiomyopathy (HCM) are highly distinct disorders leading to left ventricular hypertrophy (LVH), but whether cardiac metabolism substantially differs between these in humans remains to be elucidated.\n\nMethodWe undertook a detailed invasive (aortic root and coronary sinus) metabolic profiling in patients with severe AS and HCM in comparison to non-LVH controls, to investigate cardiac fuel selection and metabolic remodelling. These patients were assessed under different physiological states (at rest and during stress induced by pacing). The identified changes in the metabolome were further validated by metabolomic and orthogonal transcriptomic analysis, in separately recruited patient cohorts.\n\nResultsWe identified a highly discriminant metabolomic signature in severe AS characterised by striking accumulation of long-chain acylcarnitines, intermediates of long-chain transport and fatty acid metabolism, and validated this in a separate cohort. Mechanistically, we identify a down-regulation in the PPAR- transcriptional network, including expression of genes regulating FAO.\n\nConclusionsWe present a comprehensive analysis of changes in the metabolic pathways (transcriptome to metabolome) in severe AS, and its comparison to HCM. Our results demonstrate fundamental distinctions in substrate preference between AS and HCM, highlighting insufficient long-chain FAO, and the PPAR- signalling network as a specific metabolic therapeutic target in AS.

systems biology↗

bioRxiv2019

Intragenomic variability and extended sequence patterns in the mutational signature of ultraviolet light

Mutational signatures can reveal properties of underlying mutational processes and are important when assessing signals of selection in cancer. Here we describe the sequence characteristics of mutations induced by ultraviolet (UV) light, a major mutagen in several human cancers, in terms of extended (longer than trinucleotide) patterns as well as variability of the signature across chromatin states. Promoter regions display a distinct UV signature with reduced TCG>TTG transitions, and genome-wide mapping of UVB-induced DNA photoproducts (pyrimidine dimers) showed that this may be explained by decreased damage formation at hypomethylated promoter CpG sites. Further, an extended signature model encompassing additional information from longer patterns improves modeling of UV mutation rate, which may enhance discrimination between drivers and passenger events. Our study presents a refined picture of the UV signature and underscores that the characteristics of a single mutational process may vary across the genome.

genomics↗

bioRxiv2019

Elevated risk of invasive group A streptococcal disease and host genetic variation in the human leukocyte antigen locus

Invasive group A streptococcal (GAS) disease is uncommon but carries a high case-fatality rate relative to other infectious diseases. Given the ubiquity of mild GAS infections, it remains unclear why healthy individuals will occasionally develop life-threatening infections, raising the possibility of host genetic predisposition. Here, we present the results of a case-control study including 43 invasive GAS cases and 1,540 controls. Using HLA imputation and linear mixed-models, we find each copy of the HLA-DQA1*01:03 allele associates with a two-fold increased risk of disease (odds ratio 2.3, 95% confidence interval 1.3-4.4, P=0.009), an association which persists with classical HLA typing of a subset of cases and analysis with an alternative large control dataset with validated HLA data. Moreover, we propose the association is driven by the allele itself rather than the background haplotype. Overall this finding provides impetus for further investigation of the immunogenetic basis of this devastating bacterial disease.

genetics↗

bioRxiv2018

Elevated pyrimidine dimer formation at distinct genomic bases underlie promoter mutation hotspots in UV-exposed cancers

Sequencing of whole cancer genomes has revealed an abundance of recurrent mutations in gene-regulatory promoter regions, in particular in melanoma where strong mutation hotspots are observed adjacent to ETS-family transcription factor (TF) binding sites. While sometimes interpreted as functional driver events, these mutations have also been suggested to be due to locally inhibited DNA repair or, alternatively, locally increased propensity for UV damage. Here, we provide evidence that base-specific elevations in the efficacy of UV lesion formation underlie these mutations. First, we find that low-dose UV light induces mutations preferably at a known ETS promoter hotspot in cultured cells even in the absence of global or transcription-coupled nucleotide excision repair (NER), ruling out inhibited repair. Further, by genome-wide mapping of cyclobutane pyrimidine dimers (CPDs) shortly after UV exposure and thus before DNA repair, we find that ETS-related mutation hotspots exhibit a strong base-specific increase in CPD formation frequency. Analysis of a large whole genome cohort illustrates the widespread contribution of this effect to recurrent mutations in melanoma. While inhibited NER underlies a general increase in somatic mutation burden in regulatory regions, we conclude that the most recurrently mutated individual DNA bases arise instead due to locally favorable conditions for UV damage formation, thus explaining a key phenomenon in whole-genome cancer analyses.

cancer biology↗

bioRxiv2017

Dehydration Bouts Prompt Increased Activity And Blood Feeding By Mosquitoes

Mosquitoes are prone to dehydration and respond to this stress through multiple mechanisms, but previous studies have examined very specific responses and fail to provide an encompassing view of the role that dehydration has on mosquito biology. This study examined underlying changes in biology of the northern house mosquito, Culex pipiens, associated with short bouts of dehydration. We show that dehydration increased blood feeding propensity of mosquitoes, which was the result of both enhanced activity and a higher tendency to land on a host. Mosquitoes exposed to dehydrating conditions with access to water or rehydrated individuals experience no water loss and failed to display behavioral changes. RNA-seq and metabolome analyses following dehydration indicated that factors associated with energy metabolism are altered, specifically the breakdown of trehalose to yield glucose, which likely underlies changes in mosquito activity. Suppression of trehalose breakdown by RNA interference reduced phenotypes associated with dehydration. Comparable results were noted for two other mosquito species, suggesting this is a general response among mosquitoes. Lastly, field-based mesocosm studies using C. pipiens revealed that dehydrated mosquitoes were more likely to host feed, and disease modeling indicates dehydration bouts may increase transmission of West Nile virus. These results suggest that periods of dehydration prompt mosquitoes to utilize blood feeding as a mechanism to obtain water. This dehydration-induced increase in blood feeding is likely to intensify disease transmission during periods of low water availability.\n\nSignificanceDehydration stress has substantial impacts on the biology of terrestrial invertebrates. To date, no studies have elucidated the difference between dehydration exposure and realized water loss in relation to mosquito behavior and physiology. Our experiments show that direct dehydration stress increases mosquito activity and subsequent blood feeding, likely as a mechanism to locate and utilize a bloodmeal for rehydration. These dehydration-induced phenotypes were linked to altered carbohydrate metabolism that acts as a source of energy. This study provides important insight into the impact of mosquito-dehydration dynamics on disease transmission that is likely general among mosquitoes.

physiology↗