Mosquito vector proteins homologous to α1-3 galactosyl transferases of tick vectors in the context of protective immunity against malaria and hypersensitivity to vector bites

Abstract Background An epitope, Galα1-3Galβ1-4GlcNAc-R, termed α-gal, is present in glycoconjugates of New World monkeys (platyrrhines) and other mammals but not in hominoids and Old World monkeys (catarrhines). The difference is due to the inactivation of α1-3 galactosyl transferase (α1-3 GT) genes in catarrhines. Natural antibodies to α-gal are therefore developed in catarrhines but not platyrrhines and other mammals. Hypersensitivity reactions are commonly elicited by mosquito and tick vector bites. IgE antibodies against α-gal cause food allergy to red meat in persons who have been exposed to tick bites. Three enzymes synthesising the terminal α1-3-linked galactose in α-gal, that are homologous to mammalian α and β1-4 GTs but not mammalian α1-3 GTs, were recently identified in the tick vector Ixodes scapularis. IgG and IgM antibodies to α-gal are reported to protect against malaria because mosquito-derived sporozoites of malaria parasites express α-gal on their surface. This article explores the possibility that the α-gal in sporozoites are acquired from glycoconjugates synthesised by mosquitoes rather than through de novo synthesis by sporozoites. Methods The presence of proteins homologous to the three identified tick α1-3 GTs and mammalian α1-3 GTs in two important mosquito vectors, Aedes aegypti and Anopheles gambiae, as well as Plasmodium malaria parasites, was investigated by BLASTp analysis to help clarify the source of the α-gal on sporozoite surfaces. Results Anopheles gambiae and Ae. aegypti possessed several different proteins homologous to the three I. scapularis proteins with α1-3 GT activity, but not mammalian α1-3 GTs. The putative mosquito α1-3 GTs possessed conserved protein domains characteristic of glycosyl transferases. However, the genus Plasmodium lacked proteins homologous to the three I. scapularis proteins with α1-3 GT activity and mammalian α1-3 GTs. Conclusions The putative α1-3 GTs identified in the two mosquito vectors may synthesise glycoconjugates containing α-gal that can be transferred to sporozoite surfaces before they are inoculated into skin during blood feeding. The findings merit further investigation because of their implications for immunity against malaria, hypersensitivity to mosquito bites, primate evolution, and proposals for immunisation against α-gal. Graphic abstract

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The 20-hydroxyecdysone agonist, halofenozide, promotes anti-Plasmodium immunity in Anopheles gambiae via the ecdysone receptor

Scientific Reports ◽

10.1038/s41598-020-78280-8 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Rebekah A. Reynolds ◽

Hyeogsun Kwon ◽

Thiago Luiz Alves e Silva ◽

Janet Olivas ◽

Joel Vega-Rodriguez ◽

...

Keyword(s):

Anopheles Gambiae ◽

Malaria Parasite ◽

Vector Competence ◽

Direct Injection ◽

Blood Feeding ◽

Mosquito Vector ◽

Ecdysone Receptor ◽

Principal Role ◽

Cellular Immune

AbstractMosquito physiology and immunity are integral determinants of malaria vector competence. This includes the principal role of hormonal signaling in Anopheles gambiae initiated shortly after blood-feeding, which stimulates immune induction and promotes vitellogenesis through the function of 20-hydroxyecdysone (20E). Previous studies demonstrated that manipulating 20E signaling through the direct injection of 20E or the application of a 20E agonist can significantly impact Plasmodium infection outcomes, reducing oocyst numbers and the potential for malaria transmission. In support of these findings, we demonstrate that a 20E agonist, halofenozide, is able to induce anti-Plasmodium immune responses that limit Plasmodium ookinetes. We demonstrate that halofenozide requires the function of ultraspiracle (USP), a component of the canonical heterodimeric ecdysone receptor, to induce malaria parasite killing responses. Additional experiments suggest that the effects of halofenozide treatment are temporal, such that its application only limits malaria parasites when applied prior to infection. Unlike 20E, halofenozide does not influence cellular immune function or AMP production. Together, our results further demonstrate the potential of targeting 20E signaling pathways to reduce malaria parasite infection in the mosquito vector and provide new insight into the mechanisms of halofenozide-mediated immune activation that differ from 20E.

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The 20-hydroxyecdysone agonist, halofenozide, promotes anti-Plasmodium immunity in Anopheles gambiae via the ecdysone receptor

10.1101/2020.06.19.162081 ◽

2020 ◽

Author(s):

Rebekah A. Reynolds ◽

Hyeogsun Kwon ◽

Thiago Luiz Alves e Silva ◽

Janet Olivas ◽

Joel Vega-Rodriguez ◽

...

Keyword(s):

Anopheles Gambiae ◽

Malaria Parasite ◽

Vector Competence ◽

Direct Injection ◽

Blood Feeding ◽

Mosquito Vector ◽

Ecdysone Receptor ◽

Principal Role ◽

Cellular Immune

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Adaptive periodicity in the infectivity of malaria gametocytes to mosquitoes

10.1101/294942 ◽

2018 ◽

Cited By ~ 1

Author(s):

Petra Schneider ◽

Samuel S. C. Rund ◽

Natasha L. Smith ◽

Kimberley F. Prior ◽

Aidan J. O’Donnell ◽

...

Keyword(s):

Blood Feeding ◽

Blood Parasite ◽

Parasite Development ◽

Bed Nets ◽

Mosquito Vectors ◽

Plasmodium Chabaudi ◽

Malaria Parasites ◽

Rodent Malaria

AbstractThat periodicity in the biting activity of mosquito vectors explains why malaria parasites have evolved rhythms in cycles of asexual replication in the host’s blood was proposed almost 50 years ago. Yet, tests of this hypothesis have proved inconclusive. Using the rodent malaria Plasmodium chabaudi, we examine rhythms in the density and infectivity of transmission forms (gametocytes) in the host’s blood, parasite development inside mosquitoes, and onwards transmission.Moreover, we control for the confounding effects of rhythms in mosquito susceptibility. We reveal that at night, gametocytes are twice as infective to mosquitoes, despite being less numerous in the blood. This enhanced infectiousness at night interacts with mosquito rhythms to increase sporozoite burdens by almost four-fold when mosquitoes feed during their day. Thus, daytime blood-feeding (e.g. driven by the use of bed nets) may render gametocytes less infective, but this is compensated for by the greater susceptibility of mosquitoes.

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Development of a host blood meal database: de novo sequencing of hemoglobin from nine small mammals using mass spectrometry

Biological Chemistry ◽

10.1515/hsz-2011-0196 ◽

2012 ◽

Vol 393 (3) ◽

pp. 195-201 ◽

Cited By ~ 14

Author(s):

Ünige A. Laskay ◽

Jennifer Burg ◽

Erin J. Kaleta ◽

Inger-Marie E. Vilcins ◽

Sam R. Telford III ◽

...

Keyword(s):

Mass Spectrometry ◽

Lyme Disease ◽

Blood Meal ◽

De Novo ◽

Ixodes Scapularis ◽

Mammalian Host ◽

Automatic Data ◽

Tick Vector ◽

Host Blood ◽

Β Chain

Abstract We report the successful de novo sequencing of hemoglobin using a mass spectrometry-based approach combined with automatic data processing and manual validation for nine North American species with currently unsequenced genomes. The complete α and β chain of all nine mammalian hemoglobin samples used in this study were successfully sequenced. These sequences will be appended to the existing database containing all known hemoglobins to be used for identification of the mammalian host species that provided the last blood meal for the tick vector of Lyme disease, Ixodes scapularis.

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Immune factor of bacterial origin protects ticks against host skin microbes

10.1101/2020.04.10.036376 ◽

2020 ◽

Author(s):

Beth M. Hayes ◽

Atanas D. Radkov ◽

Fauna Yarza ◽

Sebastian Flores ◽

Jungyun Kim ◽

...

Keyword(s):

Lyme Disease ◽

Ixodes Scapularis ◽

Blood Feeding ◽

Toxin Gene ◽

Opportunistic Pathogens ◽

Tick Vector ◽

Immune Factor ◽

Skin Commensals ◽

Tick Borne Disease ◽

Vertebrate Hosts

SummaryHard ticks are blood-feeding arthropods that carry and transmit microbes to their vertebrate hosts1. Tick-borne disease cases have been on the rise over the last several decades, drawing much-needed attention to the molecular interplay between transmitted pathogens and their human hosts. However, far less is known about how ticks control their own microbes, which is critical for understanding how zoonotic transmission cycles persist. We previously found that ticks horizontally acquired an antimicrobial toxin gene from bacteria known as domesticated amidase effector 2 (dae2)2. Here we show that this effector from the tick vector Ixodes scapularis (Dae2Is) has structurally and biochemically diverged from ancestral bacterial representatives, expanding its antibacterial targeting range to include host skin microbes. Disruption of dae2Is increases the burden of skin-associated staphylococci within I. scapularis and adversely affects tick fitness, suggesting resistance of host microbes may be important for the parasitic blood-feeding lifestyle. In contrast, Dae2Is has no intrinsic ability to kill Borrelia burgdorferi, the tick-borne bacterium of Lyme disease. Our observations suggest that ticks have evolved to tolerate their own symbionts while resisting host skin commensals, which we discover are natural opportunistic pathogens of ticks. This work moves our understanding of vector biology beyond a human-centric view: just as tick commensals are pathogenic to humans, so too do our commensals pose a threat to ticks. These observations illuminate how a complex and mirrored set of interkingdom interactions between blood-feeding vectors, their hosts, and associated microbes can ultimately lead to disease.

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Last-come, best served? Mosquito biting order and Plasmodium transmission

10.1101/2020.04.08.031625 ◽

2020 ◽

Cited By ~ 1

Author(s):

J. Isaïa ◽

A. Rivero ◽

O. Glaizot ◽

P. Christe ◽

R. Pigeault

Keyword(s):

Malaria Transmission ◽

Malaria Parasite ◽

Blood Feeding ◽

Transmission Dynamics ◽

Vertebrate Host ◽

Mosquito Vector ◽

Temporal Heterogeneity ◽

Mosquito Vectors ◽

Temporal Fluctuations ◽

New Approaches

AbstractA pervasive characteristic of malaria parasite infection in mosquito vector populations is their tendency to be overdispersed. Understanding the mechanisms underlying the overdispersed distribution of parasites is of key importance as it may drastically impact the transmission dynamics of the pathogen. The small fraction of heavily infected individuals might serve as superspreaders and cause a disproportionate number of subsequent infections. Although multiple factors ranging from environmental stochasticity to inter-individual heterogeneity may explain parasite overdispersion, Plasmodium infection has also been observed to be highly overdispersed in inbred mosquito population maintained under standardized laboratory conditions, suggesting that other mechanisms may be at play. Here, we show that the aggregated distribution of Plasmodium within mosquito vectors is partially explained by a temporal heterogeneity in parasite infectivity triggered by the bites of blood-feeding mosquitoes. Several experimental blocks carried out with three different Plasmodium isolates have consistently shown that the transmission of the parasite increases progressively with the order of mosquito bites. Surprisingly the increase in transmission is not associated with an increase in Plasmodium replication rate or higher investment in the production of the transmissible stage (gametocyte). Adjustment of the physiological state of the gametocytes could be, however, an adaptive strategy to respond promptly to mosquito bites. Overall our data show that malaria parasite appears to be able to respond to the bites of mosquitoes to increase its own transmission at a much faster pace than initially thought (hours rather than days). Further work needs to be carried out to elucidate whether these two strategies are complementary and, particularly, what are their respective underlaying mechanisms. Understanding the processes underlying the temporal fluctuations in Plasmodium infectivity throughout vertebrate host-to-mosquito transmission is essential and could lead to the development of new approaches to control malaria transmission.Author summaryPlasmodium parasites are known for being the etiological agents of malaria and for the devastating effects they cause on human populations. A pervasive characteristic of Plasmodium infection is their tendency to be overdispersed in mosquito vector populations: the majority of mosquitoes tend to harbour few or no parasites while a few individuals harbor the vast majority of the parasite population. Understanding the mechanisms underlying Plasmodium overdispersed distribution is of key importance as it may drastically impact the transmission dynamics of the pathogen. Here, we show that the aggregated distribution of Plasmodium parasites within mosquito vectors is partially explained by a temporal heterogeneity in Plasmodium infectivity triggered by the bites of blood-feeding mosquitoes. In other words, mosquitoes that bite at the beginning of a 3h feeding session have significantly fewer parasites than those that bite towards the end. Malaria parasite is therefore capable of responding to the bites of mosquitoes to increase its own transmission at a much faster pace than thought (hours rather than days). Understanding the processes underlying the temporal fluctuations in Plasmodium infectivity throughout vertebrate host-to-mosquito transmission is essential and could lead to the development of new approaches to control malaria transmission.

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Mosquito Vector Production across Socio-Economic Divides in Baton Rouge, Louisiana

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18041420 ◽

2021 ◽

Vol 18 (4) ◽

pp. 1420

Author(s):

Rebeca de Jesús Crespo ◽

Madison Harrison ◽

Rachel Rogers ◽

Randy Vaeth

Keyword(s):

Low Income ◽

Baton Rouge ◽

Habitat Preferences ◽

Abundant Species ◽

Mosquito Larvae ◽

Mosquito Vector ◽

Mosquito Vectors ◽

Low Income Groups ◽

Socio Economic Factors

We investigated the role of socio-economic factors in the proliferation of mosquito vectors in two adjacent but socio-economically contrasting neighborhoods in Baton Rouge, LA, USA. We surveyed mosquito larvae habitat, mosquito larvae, and adult mosquitoes during the summer of 2020. We also evaluated the number of requests for mosquito abatement services in the years preceding the study for each area. While we did not find differences in terms of the most abundant species, Culex quinquefasicatus (F1,30 = 0.329, p = 0.57), we did find a higher abundance of mosquito habitats, particularly discarded tires, as well as larvae (z = 13.83, p < 0.001) and adults (F1,30 = 4.207, p = 0.049) of the species Aedes albopictus in the low-income neighborhood. In contrast, mosquito abatement requests were significantly higher in the high socio-economic neighborhood (z = −8.561, p < 0.001). This study shows how factors such as adjudicated properties, discarded tires and pest abatement requests can influence the abundance of mosquito vectors, disproportionately affecting low-income groups. This study also highlights how Aedes spp. may be better indicators than Culex spp. of socio-economic differences between nearby neighborhoods, due to their short flight range and habitat preferences, and this should be considered in future studies attempting to detect such disparities in the future.

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The regulatory genome of the malaria vector Anopheles gambiae: integrating chromatin accessibility and gene expression

NAR Genomics and Bioinformatics ◽

10.1093/nargab/lqaa113 ◽

2021 ◽

Vol 3 (1) ◽

Author(s):

José L Ruiz ◽

Lisa C Ranford-Cartwright ◽

Elena Gómez-Díaz

Keyword(s):

Gene Expression ◽

Transcriptional Regulation ◽

Anopheles Gambiae ◽

Mosquito Control ◽

Regulatory Elements ◽

Chromatin Accessibility ◽

Malaria Vectors ◽

Specific Gene ◽

Mosquito Vector ◽

Human Malaria

Abstract Anopheles gambiae mosquitoes are primary human malaria vectors, but we know very little about their mechanisms of transcriptional regulation. We profiled chromatin accessibility by the assay for transposase-accessible chromatin by sequencing (ATAC-seq) in laboratory-reared A. gambiae mosquitoes experimentally infected with the human malaria parasite Plasmodium falciparum. By integrating ATAC-seq, RNA-seq and ChIP-seq data, we showed a positive correlation between accessibility at promoters and introns, gene expression and active histone marks. By comparing expression and chromatin structure patterns in different tissues, we were able to infer cis-regulatory elements controlling tissue-specific gene expression and to predict the in vivo binding sites of relevant transcription factors. The ATAC-seq assay also allowed the precise mapping of active regulatory regions, including novel transcription start sites and enhancers that were annotated to mosquito immune-related genes. Not only is this study important for advancing our understanding of mechanisms of transcriptional regulation in the mosquito vector of human malaria, but the information we produced also has great potential for developing new mosquito-control and anti-malaria strategies.

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Genome sequence, transcriptome, and annotation of rodent malaria parasite Plasmodium yoelii nigeriensis N67

BMC Genomics ◽

10.1186/s12864-021-07555-9 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Cui Zhang ◽

Cihan Oguz ◽

Sue Huse ◽

Lu Xia ◽

Jian Wu ◽

...

Keyword(s):

Dna Sequences ◽

Malaria Parasite ◽

Vaccine Development ◽

De Novo ◽

Gene Families ◽

Plasmodium Yoelii ◽

Control Measures ◽

Effective Control ◽

Malaria Parasites ◽

Rodent Malaria

Abstract Background Rodent malaria parasites are important models for studying host-malaria parasite interactions such as host immune response, mechanisms of parasite evasion of host killing, and vaccine development. One of the rodent malaria parasites is Plasmodium yoelii, and multiple P. yoelii strains or subspecies that cause different disease phenotypes have been widely employed in various studies. The genomes and transcriptomes of several P. yoelii strains have been analyzed and annotated, including the lethal strains of P. y. yoelii YM (or 17XL) and non-lethal strains of P. y. yoelii 17XNL/17X. Genomic DNA sequences and cDNA reads from another subspecies P. y. nigeriensis N67 have been reported for studies of genetic polymorphisms and parasite response to drugs, but its genome has not been assembled and annotated. Results We performed genome sequencing of the N67 parasite using the PacBio long-read sequencing technology, de novo assembled its genome and transcriptome, and predicted 5383 genes with high overall annotation quality. Comparison of the annotated genome of the N67 parasite with those of YM and 17X parasites revealed a set of genes with N67-specific orthology, expansion of gene families, particularly the homologs of the Plasmodium chabaudi erythrocyte membrane antigen, large numbers of SNPs and indels, and proteins predicted to interact with host immune responses based on their functional domains. Conclusions The genomes of N67 and 17X parasites are highly diverse, having approximately one polymorphic site per 50 base pairs of DNA. The annotated N67 genome and transcriptome provide searchable databases for fast retrieval of genes and proteins, which will greatly facilitate our efforts in studying the parasite biology and gene function and in developing effective control measures against malaria.

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Avian Malaria Parasites Share Congeneric Mosquito Vectors

Journal of Parasitology ◽

10.1645/ge-2060.1 ◽

2010 ◽

Vol 96 (1) ◽

pp. 144-151 ◽

Cited By ~ 87

Author(s):

M. Kimura ◽

J. M. Darbro ◽

L. C. Harrington

Keyword(s):

Avian Malaria ◽

Mosquito Vectors ◽

Malaria Parasites ◽

Avian Malaria Parasites

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