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Zwiebel, L.

Publications and source records attributed to Zwiebel, L..

5 recordsLinked to original sources

Transcriptome Profiles of Anopheles gambiae Harboring Natural Low-Level Plasmodium Infection Reveal Adaptive Advantages for the Mosquito

Anopheline mosquitoes are the sole vectors for the Plasmodium pathogens responsible for malaria, which is among the oldest and most devastating of human diseases. The continuing global impact of malaria reflects the evolutionary success of a complex vector-pathogen relationship that accordingly has been the long-term focus of both debate and study. An open question in the biology of malaria transmission is the impact of naturally occurring low-level Plasmodium infections of the vector on the mosquitos health and longevity as well as critical behaviors such as host- preference/seeking. To begin to answer this, we have completed a comparative RNAseq-based transcriptome profile study examining the effect of biologically salient, salivary gland transmission- stage Plasmodium infection on the molecular physiology of Anopheles gambiae s.s. head, sensory appendage, and salivary glands. When compared with their uninfected counterparts, Plasmodium infected mosquitoes exhibit increased transcript abundance of genes associated with olfactory acuity as well as a range of synergistic processes that align with increased fitness based on both anti-aging and reproductive advantages. Taken together, these data argue against the long-held paradigm that malaria infection is pathogenic for anophelines and, instead, suggests there are biological and evolutionary advantages for the mosquito that drive the preservation of its high vectorial capacity.

molecular biology

Discrete Roles of the Ir76b Ionotropic Co-Receptor Impact Olfaction, Blood Feeding, and Mating in the Malaria Vector Mosquito Anopheles coluzzii

Anopheline mosquitoes rely on their highly sensitive chemosensory apparatus to detect diverse chemical stimuli that drive the host-seeking and blood-feeding behaviors required to vector pathogens for malaria and other diseases. This process incorporates a variety of chemosensory receptors and transduction pathways. We have used advanced in vivo gene-editing and -labelling approaches to localize and functionally characterize the ionotropic co-receptor AcIr76b in the malaria mosquito Anopheles coluzzii, where it impacts both olfactory and gustatory systems. AcIr76b has a broad expression pattern in female adult antennal grooved pegs, T1 and T2 sensilla on the labellum, stylets, and tarsi, as well as the larval sensory peg. AcIr76b is co-localized with the Orco odorant receptor (OR) co-receptor in a subset of cells across the female antennae and labella. In contrast to Orco and Ir8a, chemosensory co-receptors that appear essential for the activity of their respective sets of chemosensory neurons in mosquitoes, AcIr76b-/- mutants maintain wild-type peripheral responses to volatile amines on the adult palps, labellum, and the larval sensory cone. Interestingly, AcIr76b-/- mutants display significantly increased responses to amines in antennal grooved peg sensilla while coeloconic sensilla reveal significant deficits in responses to several acids and amines. Behaviorally, AcIr76b mutants manifest significantly female-specific insemination deficits and, although AcIr76b-/- mutant females are able to locate, alight, and probe artificial blood hosts, they are incapable of blood feeding successfully. Taken together, our study reveals a multi-dimensional functionality of Ir76b in Anopheline olfactory and gustatory pathways that directly impacts the vectorial capacity of these mosquitoes. SummaryChemosensory receptors play crucial roles across mosquito lifecycles where they often form functional complexes that require cognate co-receptors. To better understand mosquito chemosensory pathways in the malaria vector mosquito An. coluzzii we have utilized advanced gene editing approaches to localize and functionally characterize the ionotropic receptor co-receptor AcIr76b. Expression of AcIr76b was observed in antennal grooved pegs and other accessory olfactory appendages. Mutagenesis of AcIr76b uncovers both reduced and elevated neuronal responses to amines, which suggests a role in response modulation. In addition to olfactory phenotypes, AcIr76b mutants display significantly impaired mating and blood feeding capabilities. Our data reveals discrete roles of AcIr76b across olfactory and gustatory pathways and shed lights on the potential molecular target for vector control strategies.

neuroscience

Mutagenesis of the Ammonium Transporter AcAmt Reveals a Reproductive Role and a Novel Ammonia-Sensing Mechanism in the Malaria Vector Mosquito Anopheles coluzzii

Anopheline mosquitoes are the sole vectors of malaria and rely on olfactory cues for host seeking in which ammonia derived from human sweat plays an essential role. To investigate the function of the Anopheles coluzzii ammonium transporter (AcAmt) in the mosquito olfactory system, we generated an AcAmt null mutant line using CRISPR/Cas9. AcAmt-/- mutants displayed a series of novel phenotypes compared with wild-type mosquitoes including significantly lower insemination rates during mating and increased mortality during eclosion. Furthermore, AcAmt-/- males showed significantly lower sugar consumption while AcAmt-/- females and pupae displayed significantly higher ammonia levels than their wild-type counterparts. Surprisingly, in contrast to previous studies in Drosophila that revealed that the mutation of the ammonium transporter (DmAmt) induces a dramatic reduction of ammonia responses in antennal coeloconic sensilla, no significant differences were observed across a range of peripheral sensory neuron responses to ammonia and other odorants between wild-type and AcAmt-/- females. Taken together, these data support the existence of a unique ammonia-sensing mechanism in mosquitoes and that the ammonium transporter may be an important molecular target for vector control. Key MessagesO_LIMutagenesis of An. coluzzii ammonium transporter AcAmt followed by comprehensive electrophysiological investigation suggest a novel ammonia-sensing pathway in Anopheles mosquitoes. C_LIO_LIAcAmt-/- mutants displayed significant deficiencies in reproduction and eclosion, which are likely due to elevated ammonia levels and reduced ability of sugar feeding. C_LIO_LIAn. coluzzii coeloconic sensilla primarily detect amines and acids. C_LI

neuroscience

Neuronal Odor Coding in the Larval Sensory Cone of Anopheles coluzzii: Complex Responses from a Simple System

Anopheles mosquitoes are the sole vectors of malaria and other diseases that represent significant threats to global public health. While adult female mosquitoes are responsible for disease transmission, the pre-adult larval stages of the malaria vector Anopheles coluzzii and other mosquitoes rely on a broad spectrum of sensory cues to navigate their aquatic habitats efficiently to avoid predators and search for food. Of these, mosquito larvae rely heavily on volatile chemical signals that directly activate their olfactory apparatus. Because most studies on mosquito olfaction focus on adults, a paucity of attention has been given to the larval olfactory system, in which the peripheral components are associated with the sensory cone of the larval antennae. To address this, we have investigated the electrophysiological response profile of the larval sensory cone in Anopheles mosquitoes. We found that the larval sensory cone is particularly tuned to alcohols, thiazoles and heterocyclics. Furthermore, these responses can be assigned to discrete groups of sensory cone neurons with distinctive, dose-dependent odorant-response profiles that also provide larvae with the ability to discriminate among compounds with similar chemical structures. A correlation analysis was conducted to determine the relationship between specific larval chemosensory receptors and the response profiles of sensory cone neuron groups. These studies reveal that the larval sensory cone is a highly sophisticated organ that is sensitive to a broad range of compounds and is capable of a remarkable degree of chemical discrimination. Taken together, this study presents critical insights into olfactory coding processes in An. coluzzii larvae that further our understanding of larval chemical ecology and will contribute to the development of novel larval-based strategies and tools for mosquito control and the reduction of vector-borne disease transmission.

neuroscience

Gene Editing Reveals Obligate and Modulatory Components of the CO2 Receptor Complex in the Malaria Vector Mosquito, Anopheles coluzzii

The sensitivity to volatile carbon dioxide (CO2) produced by humans and other animals is a critical component in the host preference behaviors of the malaria vector mosquito Anopheles coluzzii. The molecular receptors responsible for the ability to sense CO2 are encoded by three putative gustatory receptor (Gr) genes (Gr22,23,24) which are expressed in a distinctive array of sensory neurons housed in maxillary palp capitate peg sensilla of An. coluzzii. Despite the identification of these components and subsequent studies, there is a paucity of understanding regarding the respective roles of these three GRs in the mosquitos CO2 transduction process. To address this, we have used CRISPR/Cas9-based gene editing techniques combined with in vivo electrophysiological recordings to directly examine the role of Gr22,23,24 in detecting CO2 in An. coluzzii. These studies reveal that both Gr23 and Gr24 are absolutely required to maintain in vivo CO2 sensitivity while, in contrast, Gr22 knock out mutants are still able to respond to CO2 stimuli albeit with significantly weaker sensitivity. Our data supports a model in which Gr22 plays a modulatory role to enhance the functionality of Gr23/24 complexes that are responsible for CO2 sensitivity of mosquitoes.

neuroscience