Breathprinting Reveals Malaria-Associated Biomarkers and Mosquito Attractants.
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ABSTRACT:
SUBMITTER: Schaber CL
PROVIDER: S-EPMC6279169 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Current evidence suggests that malaria infection could alter patient breath metabolites, a phenomenon that could be exploited to create a breath-based diagnostic test. Indications include the preferential attraction of the Anopheles mosquito vector upon infection and a distinct breath profile with the progression of experimental, sub-microscopic malaria. However, these observations have yet to be extended to the clinic. To investigate whether natural human malaria infection leads to a characteristic breath profile, we performed a field study in Malawi. Breath volatiles from pediatric patients with and without uncomplicated falciparum malaria were analyzed by thermal desorption-gas chromatography/mass spectrometry. Using an unbiased, correlation-based analysis, we find that children with malaria have a distinct shift in overall breath composition. Leveraging these differences, highly accurate classification of infection status was achieved with a suite of six compounds. In addition, we find that malaria-infected children have significantly higher breath levels of two mosquito-attractant terpenes, α-pinene and 3-carene. Thus, our work attests to the viability of breath analysis for malaria diagnosis, identifies candidate compounds for follow-up studies, and identifies biologically plausible chemical mediators for increased mosquito attraction to malaria-infected patients.
2017-10-08 | ST000883 | MetabolomicsWorkbench
Project description:The malaria parasite Plasmodium falciparum contains a nonphotosynthetic plastid organelle that possesses plant-like metabolic pathways. Plants use the plastidial isoprenoid biosynthesis pathway to produce volatile odorants, known as terpenes. In this work, we describe the volatile chemical profile of cultured malaria parasites. Among the identified compounds are several plant-like terpenes and terpene derivatives, including known mosquito attractants. We establish the molecular identity of the odorant receptors of the malaria mosquito vector Anopheles gambiae, which responds to these compounds. The malaria parasite produces volatile signals that are recognized by mosquitoes and may thereby mediate host attraction and facilitate transmission. Malaria is a key global health concern. Mosquitoes that transmit malaria are more attracted to malaria parasite-infected mammalian hosts. These studies aimed to understand the chemical signals produced by malaria parasites; such an understanding may lead to new transmission-blocking strategies or noninvasive malaria diagnostics.
| S-EPMC4453533 | biostudies-literature
Project description:BackgroundBritish mosquito population distribution, abundance, species composition and potential for mosquito disease transmission are intimately linked to the physical environment. The presence of ponds and water storage can significantly increase the density of particular mosquito species in the garden. Culex pipiens is the mosquito most commonly found in UK gardens and a potential vector of West Nile Virus WNV, although the current risk of transmission is low. However any factors that significantly change the distribution and population of C. pipiens are likely to impact subsequent risk of disease transmission. Pond dyes are used to control algal growth and improve aesthetics of still water reflecting surrounding planting. However, it is well documented that females of some species of mosquito prefer to lay eggs in dark water and/or containers of different colours and we predict that dyed ponds will be attractive to Culex mosquitoes.MethodsBlack pond dye was used in oviposition choice tests using wild-caught gravid C. pipiens. Larvae from wild-caught C. pipiens were also reared in the pond dye to determine whether it had any impact on survival. An emergence trap caught any adults that emerged from the water. Water butts (80 L) were positioned around university glasshouses and woodland and treated with black pond dye or left undyed. Weekly sampling over a six month period through summer and autumn was performed to quantified numbers of larvae and pupae in each treatment and habitat.ResultsGravid female Culex mosquitoes preferred to lay eggs in dyed water. This was highly significant in tests conducted under laboratory conditions and in a semi-field choice test. Despite this, survivorship in black dyed water was significantly reduced compared to undyed water. Seasonal analysis of wild larval and pupal numbers in two habitats with and without dye showed no impact of dye but a significant impact of season and habitat. Mosquitoes were more successful, with significantly higher numbers of pupae, in the habitat where they had vegetation cover and shade.DiscussionOur study has raised some interesting possibilities; one is that where used, pond dyes may be encouraging mosquitoes to breed in gardens in close proximity to people. Considering the concerns over potential future spread of disease in urban environments, this as well as shading of ponds and water butts, should inform future advice over reducing mosquito breeding and spread.
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Project description:Sampling for adult mosquito populations is a means of evaluating the efficacy of vector control operations. The goal of this study was to evaluate and identify the most efficacious mosquito traps and combinations of attractants for malaria vector surveillance along the Thai-Myanmar border.In the first part of the study, the BG-Sentinel™ Trap (BGS Trap) and Centers for Disease Control and Prevention miniature light trap (CDC LT) baited with different attractants (BG-lure® and CO2) were evaluated using a Latin square experimental design. The six configurations were BGS Trap with BG-lure, BGS Trap with BG-lure plus CO2, BGS Trap with CO2, CDC LT with BG-lure, CDC LT with BG lure plus CO2, and CDC LT with CO2. The second half of the study evaluated the impact of light color on malaria vector collections. Colors included the incandescent bulb, ultraviolet (UV) light-emitting diode (LED), green light stick, red light stick, green LED, and red LED.A total of 8638 mosquitoes consisting of 42 species were captured over 708 trap-nights. The trap types, attractants, and colored lights affected numbers of female anopheline and Anopheles minimus collected (GLM, P < 0.01). Results revealed that BGS Trap captured many anophelines but was significantly less than the CDC LT. The CDC LT, when baited with BG-lure plus CO2 captured the greatest number of anopheline females with a catch rate significantly higher than the CDC LT baited with BG-lure or CO2 alone (P < 0.05). The number of anopheline females collected from the CDC LT baited with CO2 was greater than the CDC LT baited with BG-lure (646 vs 409 females). None of the alternative lights evaluated exceeded the performance of the incandescent light bulb in terms of the numbers of anopheline and An. minimus collected.We conclude that the CDC LT augmented with an incandescent light shows high potential for malaria vector surveillance when baited with CO2 and the BG-lure in combination and can be effectively used as the new gold standard technique for collecting malaria vectors in Thailand.
| S-EPMC5547504 | biostudies-other
Project description:In addition to its primary function as an insect repellent, DEET has many "off-label" properties, including a deterrent effect on the attraction of gravid female mosquitoes. DEET negatively affects oviposition sites. While deorphanizing odorant receptors (ORs) using the Xenopus oocyte recording system, we have previously observed that DEET generated outward (inhibitory) currents on ORs sensitive to oviposition attractants. Here, we systematically investigated these inhibitory currents. We recorded dose-dependent outward currents elicited by DEET and other repellents on ORs from Culex quinquefasciatus, Aedes aegypti, and Anopheles gambiae. Similar responses were observed with other plant-derived and plant-inspired compounds, including methyl jasmonate and methyl dihydrojasmolate. Inward (regular) currents elicited by skatole upon activation of CquiOR21 were modulated when this oviposition attractant was coapplied with a repellent. Compounds that generate outward currents in ORs sensitive to oviposition attractants elicited inward currents in a DEET-sensitive receptor, CquiOR136. The best ligand for this receptor, methyl dihydrojasmolate, showed repellency activity but was not as strong as DEET in our test protocol.
| S-EPMC6752049 | biostudies-literature
Project description:Insect odorant receptors (ORs) are heteromers comprised of highly variable odorant-binding subunits associated with one conserved co-receptor. They are potential molecular targets for the development of novel mosquito attractants and repellents. ORs have been identified in the malaria mosquito, Anopheles gambiae, and in the yellow fever mosquito, Aedes aegypti. However, they are still unknown in the Southern house mosquito, Culex quinquefasciatus, which transmits pathogens that cause human diseases throughout the world, including West Nile Virus in the United States.We have employed a combination of bioinformatics, molecular cloning and electrophysiology approaches to identify and characterize the response profile of an OR in Cx. quinquefasciatus. First, we have unveiled a large multigenic family of one-hundred-fifty-eight putative ORs in this species, including a subgroup of conserved ORs in three mosquito species. Using the Xenopus oocytes expression system, we have determined the response profile of CquiOR2, an antennae-specific OR, which shares high identity with putative orthologs in Anopheles gambiae (AgamOR2) and Aedes aegypti (AaegOR2).We show that CquiOR2 is highly sensitive to indole, an oviposition attractant for Cx. quinquefasciatus. The response profile of CquiOR2 expressed in Xenopus oocytes resembles that of an olfactory receptor neuron housed in the antennal short blunt-tipped sensilla (A2) of Cx. quinquefasciatus, which are natural detectors for oviposition attractants. This first Culex OR de-orphanized is, therefore, a potential molecular target for screening oviposition attractants.
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Project description:Acquisition of Elizabethkingia infections in intensive care units (ICUs) has risen in the past decade. Treatment of Elizabethkingia infections is challenging due to the lack of effective therapeutic regimens, leading to a high mortality rate. Elizabethkingia infections have long been attributed to Elizabethkingia meningoseptica. Recently, we used whole-genome sequencing to reveal that E. anophelis is the pathogenic agent for an Elizabethkingia outbreak at two ICUs. We performed comparative genomic analysis of seven hospital-isolated E. anophelis strains with five available Elizabethkingia spp. genomes deposited in the National Center for Biotechnology Information Database. A pan-genomic approach was applied to identify the core- and pan-genome for the Elizabethkingia genus. We showed that unlike the hospital-isolated pathogen E. meningoseptica ATCC 12535 strain, the hospital-isolated E. anophelis strains have genome content and organization similar to the E. anophelis Ag1 and R26 strains isolated from the midgut microbiota of the malaria mosquito vector Anopheles gambiae. Both the core- and accessory genomes of Elizabethkingia spp. possess genes conferring antibiotic resistance and virulence. Our study highlights that E. anophelis is an emerging bacterial pathogen for hospital environments.
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Project description:Blood feeding, or hematophagy, is a behavior exhibited by female mosquitoes required both for reproduction and for transmission of pathogens. We determined the expression patterns of 3,068 ESTs, representing ~2,000 unique gene transcripts using cDNA microarrays in adult female Anopheles gambiae at selected times during the first two days following blood ingestion, at 5 and 30 min during a 40 minute blood meal and at 0, 1, 3, 5, 12, 16, 24 and 48 hours after completion of the blood meal and compared their expression to transcript levels in mosquitoes with access only to a sugar solution.In blood-fed mosquitoes, 413 unique transcripts, approximately 25% of the total, were expressed at least two-fold above or below their levels in the sugar-fed mosquitoes, at one or more time points. These differentially expressed gene products were clustered using k-means clustering into Early Genes, Middle Genes, and Late Genes, containing 144, 130, and 139 unique transcripts, respectively. Several genes from each group were analyzed by quantitative real-time PCR in order to validate the microarray results.The expression patterns and annotation of the genes in these three groups (Early, Middle, and Late genes) are discussed in the context of female mosquitoes' physiological responses to blood feeding, including blood digestion, peritrophic matrix formation, egg development, and immunity.
| S-EPMC546002 | biostudies-literature
Project description:Malaria mortality rates in sub-Saharan Africa have declined significantly in recent years as a result of increased insecticide-treated bed net (ITN) usage. A major challenge to further progress is the emergence and spread of insecticide resistance alleles in the Anopheles mosquito vectors, like An. coluzzii. A non-synonymous mutation in the para voltage-gated sodium channel gene reduces pyrethroid-binding affinity, resulting in knockdown resistance (kdr). Metabolic mechanisms of insecticide resistance involving detoxification genes like cytochrome P450 genes, carboxylesterases, and glutathione S-transferases are also important. As some gene activity is tissue-specific and/or environmentally induced, gene regulatory variation may be overlooked when comparing expression from whole mosquito bodies under standard rearing conditions.We detected complex insecticide resistance in a 2014 An. coluzzii colony from southern Mali using bottle bioassays. Additional bioassays involving recombinant genotypes from a cross with a relatively susceptible 1995 An. coluzzii colony from Mali confirmed the importance of kdr and associated increased permethrin resistance to the CYP9K1 locus on the X chromosome. Significant differential expression of CYP9K1 was not observed among these colonies in Malpighian tubules. However, the P450 gene CYP6Z1 was overexpressed in resistant individuals following sublethal permethrin exposure and the carboxylesterase gene COEAE5G was constitutively overexpressed.The significant P450-related insecticide resistance observed in the 2014 An. coluzzii colony indicates that ITNs treated with the P450 inhibitor piperonyl butoxide (PBO) would be more effective in this region. The known insecticide resistance gene CYP6Z1 was differentially expressed exclusively in the context of sublethal permethrin exposure, highlighting the importance of tissue-specificity and environmental conditions in gene expression studies. The increased activity of the carboxylesterase COEAE5G in the resistant An. coluzzii colony suggests resistance to other insecticides like organophosphates. Additional gene expression studies involving other tissues (e.g. fat body) would provide a more comprehensive view of genes underlying metabolic insecticide resistance in An. coluzzii from Mali. Identifying genetic markers linked to these regulatory alleles is an important next step that would substantially improve insecticide resistance surveillance and population genetic studies in this important vector species.
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