13 results on '"Kelsey L. Adams"'
Search Results
2. Staphylococcus aureus produces pain through pore-forming toxins and neuronal TRPV1 that is silenced by QX-314
- Author
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Kimbria J. Blake, Pankaj Baral, Tiphaine Voisin, Ashira Lubkin, Felipe Almeida Pinho-Ribeiro, Kelsey L. Adams, David P. Roberson, Yuxin C. Ma, Michael Otto, Clifford J. Woolf, Victor J. Torres, and Isaac M. Chiu
- Subjects
Science - Abstract
Bacterial infection can cause pain but the underlying mechanism is unclear. This study shows pain induced in mice by methicillin-resistant Staphylococcus aureus infection is mediated by bacterial pore-forming toxins, and a sodium channel blocker QX-314 can alleviate infection-associated pain.
- Published
- 2018
- Full Text
- View/download PDF
3. Development of circulating isolates of Plasmodium falciparum is accelerated in Anopheles vectors with reduced reproductive output.
- Author
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Kristine Werling, Maurice A Itoe, W Robert Shaw, Raymond Dombagniro Hien, Bali Jean Bazié, Fofana Aminata, Kelsey L Adams, Bienvenu Seydou Ouattara, Mathias Sanou, Duo Peng, Roch K Dabiré, Dari F Da, Rakiswendé Serge Yerbanga, Abdoulaye Diabaté, Thierry Lefèvre, and Flaminia Catteruccia
- Subjects
Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
Anopheles gambiae and its sibling species Anopheles coluzzii are the most efficient vectors of the malaria parasite Plasmodium falciparum. When females of these species feed on an infected human host, oogenesis and parasite development proceed concurrently, but interactions between these processes are not fully understood. Using multiple natural P. falciparum isolates from Burkina Faso, we show that in both vectors, impairing steroid hormone signaling to disrupt oogenesis leads to accelerated oocyst growth and in a manner that appears to depend on both parasite and mosquito genotype. Consistently, we find that egg numbers are negatively linked to oocyst size, a metric for the rate of oocyst development. Oocyst growth rates are also strongly accelerated in females that are in a pre-gravid state, i.e. that fail to develop eggs after an initial blood meal. Overall, these findings advance our understanding of mosquito-parasite interactions that influence P. falciparum development in malaria-endemic regions.
- Published
- 2024
- Full Text
- View/download PDF
4. Selection for insecticide resistance can promote Plasmodium falciparum infection in Anopheles.
- Author
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Kelsey L Adams, Emily K Selland, Bailey C Willett, John W Carew, Charles Vidoudez, Naresh Singh, and Flaminia Catteruccia
- Subjects
Immunologic diseases. Allergy ,RC581-607 ,Biology (General) ,QH301-705.5 - Abstract
Insecticide resistance is under strong selective pressure in Anopheles mosquitoes due to widespread usage of insecticides in vector control strategies. Resistance mechanisms likely cause changes that profoundly affect mosquito physiology, yet it remains poorly understood how selective pressures imposed by insecticides may alter the ability of the mosquito to host and transmit a Plasmodium infection. From pyrethroid-resistant field-derived Anopheles gambiae s.l. mosquitoes, we established resistant (RES) and susceptible (SUS) colonies by either selection for, or loss of insecticide resistance. We show increased oocyst intensity and growth rate as well as increased sporozoite prevalence and intensity in RES compared to SUS females infected with Plasmodium falciparum. The increase in infection intensity in RES females was not associated with the presence of the kdrL1014F mutation and was not impacted by inhibition of Cytochrome P450s. The lipid transporter lipophorin (Lp), which was upregulated in RES compared to SUS, was at least partly implicated in the increased intensity of P. falciparum but not directly involved in the insecticide resistance phenotype. Interestingly, we observed that although P. falciparum infections were not affected when RES females were exposed to permethrin, these females had decreased lipid abundance in the fat body following exposure, pointing to a possible role for lipid mobilization in response to damage caused by insecticide challenge. The finding that selection for insecticide resistance can increase P. falciparum infection intensities and growth rate reinforces the need to assess the overall impact on malaria transmission dynamics caused by selective pressures mosquitoes experience during repeated insecticide challenge.
- Published
- 2023
- Full Text
- View/download PDF
5. Using an antimalarial in mosquitoes overcomes Anopheles and Plasmodium resistance to malaria control strategies.
- Author
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Douglas G Paton, Alexandra S Probst, Erica Ma, Kelsey L Adams, W Robert Shaw, Naresh Singh, Selina Bopp, Sarah K Volkman, Domombele F S Hien, Prislaure S L Paré, Rakiswendé S Yerbanga, Abdoullaye Diabaté, Roch K Dabiré, Thierry Lefèvre, Dyann F Wirth, and Flaminia Catteruccia
- Subjects
Immunologic diseases. Allergy ,RC581-607 ,Biology (General) ,QH301-705.5 - Abstract
The spread of insecticide resistance in Anopheles mosquitoes and drug resistance in Plasmodium parasites is contributing to a global resurgence of malaria, making the generation of control tools that can overcome these roadblocks an urgent public health priority. We recently showed that the transmission of Plasmodium falciparum parasites can be efficiently blocked when exposing Anopheles gambiae females to antimalarials deposited on a treated surface, with no negative consequences on major components of mosquito fitness. Here, we demonstrate this approach can overcome the hurdles of insecticide resistance in mosquitoes and drug resistant in parasites. We show that the transmission-blocking efficacy of mosquito-targeted antimalarials is maintained when field-derived, insecticide resistant Anopheles are exposed to the potent cytochrome b inhibitor atovaquone, demonstrating that this drug escapes insecticide resistance mechanisms that could potentially interfere with its function. Moreover, this approach prevents transmission of field-derived, artemisinin resistant P. falciparum parasites (Kelch13 C580Y mutant), proving that this strategy could be used to prevent the spread of parasite mutations that induce resistance to front-line antimalarials. Atovaquone is also highly effective at limiting parasite development when ingested by mosquitoes in sugar solutions, including in ongoing infections. These data support the use of mosquito-targeted antimalarials as a promising tool to complement and extend the efficacy of current malaria control interventions.
- Published
- 2022
- Full Text
- View/download PDF
6. Selection for insecticide resistance can promotePlasmodium falciparuminfection inAnopheles
- Author
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Kelsey L. Adams, Emily K. Selland, Bailey C. Willett, John W. Carew, Charles Vidoudez, Naresh Singh, and Flaminia Catteruccia
- Abstract
Insecticide resistance is under strong selective pressure inAnophelesmosquitoes due to widespread usage of insecticides in vector control strategies. Resistance mechanisms likely cause changes that profoundly affect mosquito physiology, yet it remains poorly understood how selective pressures imposed by insecticides may alter the ability of the mosquito to host and transmit aPlasmodiuminfection. From pyrethroid-resistant field-derivedAnopheles gambiae s.l. mosquitoes, we performed selection experiments to establish resistant (RES) and susceptible (SUS) colonies by either selection for, or loss of, insecticide resistance. We show increased prevalence, intensity, and oocyst growth rate ofPlasmodium falciparuminfection in RES females compared to SUS. The increase in infection intensity in RES females was not associated with the presence of thekdrL1014F mutation, and was not impacted by inhibition of Cytochrome P450s. The lipid transporter lipophorin (Lp), which was upregulated in RES compared to SUS, was at least partly implicated in the increased intensity ofP. falciparumbut not directly in the insecticide resistance phenotype. Interestingly, we observed that althoughP. falciparuminfections were not affected when RES females were exposed to permethrin, these females had decreased lipid abundance in the fat body following exposure, pointing to a possible role for lipid mobilization in response to damage caused by insecticide challenge. The finding that selection for insecticide resistance can increaseP. falciparuminfection intensities and growth rate reinforces the need to assess the overall impact on malaria transmission dynamics of selective pressures mosquitoes experience during repeated insecticide challenge.Significance StatementInsecticide resistance poses a severe threat for malaria control. Resistance to pyrethroid insecticides, the active component of most insecticide-treated nets, is now widespread in sub-Saharan Africa, reducing the efficacy of these crucial tools. Despite significant research characterizing insecticide resistance mechanisms, it remains unknown how these traits influencePlasmodium falciparuminfections in malaria-transmittingAnophelesmosquitoes. We established a pyrethroid-resistant and pyrethroid-susceptible population ofAnopheles gambiaederived from the same genetic background and performed experimental infections withP. falciparum. We found that the pyrethroid-resistant population was more supportive of malaria parasites compared to the susceptible population. This was not caused by well-known insecticide resistance mechanisms, but linked with a lipid transporter, lipophorin, which may play an indirect role in resistance.
- Published
- 2022
7. Cuticular hydrocarbons are associated with mating success and insecticide resistance in malaria vectors
- Author
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Abdoulaye Niang, Adam South, Roch K. Dabiré, Jennifer P. Wang, Kristine Werling, Maurice A. Itoe, W. Robert Shaw, Kelsey L. Adams, Douglas G. Paton, Flaminia Catteruccia, Abdoulaye Diabaté, Simon P. Sawadogo, and Charles Nignan
- Subjects
0106 biological sciences ,0301 basic medicine ,Insecticides ,Behavioural ecology ,QH301-705.5 ,Population ,Medicine (miscellaneous) ,Zoology ,Mosquito Vectors ,Biology ,010603 evolutionary biology ,01 natural sciences ,Article ,Pheromones ,General Biochemistry, Genetics and Molecular Biology ,Insecticide Resistance ,Sexual Behavior, Animal ,03 medical and health sciences ,chemistry.chemical_compound ,Anopheles ,Burkina Faso ,Pyrethrins ,parasitic diseases ,Animals ,Biology (General) ,Mating ,education ,Malaria vector ,reproductive and urinary physiology ,education.field_of_study ,Pyrethroid ,Resistance (ecology) ,Reproduction ,fungi ,Hydrocarbons ,Malaria ,030104 developmental biology ,Mate choice ,Sexual selection ,chemistry ,Insecticide resistance ,behavior and behavior mechanisms ,Anopheles coluzzii ,Insecticide resistance management ,Epidermis ,General Agricultural and Biological Sciences ,Entomology - Abstract
Anopheles coluzzii females, important malaria vectors in Africa, mate only once in their lifetime. Mating occurs in aerial swarms with a high male-to-female ratio, where traits underlying male mating success are largely unknown. Here, we investigated whether cuticular hydrocarbons (CHCs) influence mating success in natural mating swarms in Burkina Faso. As insecticides are widely used in this area for malaria control, we also determined whether CHCs affect insecticide resistance levels. We find that mated males have higher CHC abundance than unmated controls, suggesting CHCs could be determinants of mating success. Additionally, mated males have higher insecticide resistance under pyrethroid challenge, and we show a link between resistance intensity and CHC abundance. Taken together, our results suggest that CHC abundance may be subject to sexual selection in addition to selection by insecticide pressure. This has implications for insecticide resistance management, as these traits may be sustained in the population due to their benefits in mating even in the absence of insecticides., In this study, Adams et al. investigate the effect of cuticular hydrocarbons on mating success in natural mosquito mating swarms. These hydrocarbons confer both higher mating success and increased resistance to pyrethroid, suggesting sexual selection for insecticide resistance in this population secondary to mating success.
- Published
- 2021
8. Wolbachia cifBinduces cytoplasmic incompatibility in the malaria mosquito
- Author
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Flaminia Catteruccia, Daniel G. Abernathy, Maurice A. Itoe, Kelsey L. Adams, Bailey C. Willett, and Emily K. Selland
- Subjects
Genetics ,biology ,Sterility ,Anopheles gambiae ,Anopheles ,medicine ,Parasitism ,Wolbachia ,biology.organism_classification ,medicine.disease ,Phenotype ,Cytoplasmic incompatibility ,Malaria - Abstract
Wolbachiainfections are a fascinating example of reproductive parasitism with strong potential to combat vector-borne diseases, due to their combined ability to spread in insect populations and block pathogen replication. Though theWolbachiafactors mediating the notable reproductive manipulation cytoplasmic incompatibility (CI) have now been identified as prophage WO genescifAandcifB, the relative role of these genes is still intensely debated, with different models claiming that CI requires either both factors orcifBalone. Here we investigated whethercifAandcifBare sufficient to induce conditional sterility in the major malaria vectorAnopheles gambiae, a species that appears to have limited susceptibility to invasion byWolbachia. We report that CI can be fully recapitulated in these mosquitoes, and thatcifBis sufficient to cause this reproductive manipulation.cifB-induced sterility is fully rescued by high levels ofcifAexpression in females. Surprisingly, however, whencifAis highly expressed in males alongsidecifB, the CI phenotype is attenuated.cifBstrongly impairs fertility also when expressed in the female germline, again mitigated bycifA. These data support a system wherebycifBandcifAmust be fine-tuned to exercise CI and rescue, respectively, possibly explaining the limited success ofWolbachiaat invadingAnopheles. Our findings pave the way towards facilitatingWolbachiainfections in anopheline vectors, for use in malaria control strategies.
- Published
- 2021
9. Wolbachia cifB induces cytoplasmic incompatibility in the malaria mosquito vector
- Author
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Bailey C. Willett, Kelsey L. Adams, Flaminia Catteruccia, Daniel G. Abernathy, Maurice A. Itoe, and Emily K. Selland
- Subjects
Microbiology (medical) ,Male ,Aedes albopictus ,Molecular biology ,Sterility ,Anopheles gambiae ,Immunology ,Extrachromosomal Inheritance ,Mosquito Vectors ,Applied Microbiology and Biotechnology ,Microbiology ,Article ,03 medical and health sciences ,Sterile insect technique ,0302 clinical medicine ,Bacterial Proteins ,Aedes ,parasitic diseases ,Anopheles ,Genetics ,medicine ,Animals ,Infertility, Male ,030304 developmental biology ,0303 health sciences ,biology ,fungi ,Cell Biology ,biology.organism_classification ,medicine.disease ,Virology ,3. Good health ,Malaria ,Vector (epidemiology) ,Wolbachia ,Female ,Microbial genetics ,030217 neurology & neurosurgery ,Cytoplasmic incompatibility - Abstract
Wolbachia, a maternally inherited intracellular bacterial species, can manipulate host insect reproduction by cytoplasmic incompatibility (CI), which results in embryo lethality in crosses between infected males and uninfected females. CI is encoded by two prophage genes, cifA and cifB. Wolbachia, coupled with the sterile insect technique, has been used in field trials to control populations of the dengue vector Aedes albopictus, but CI-inducing strains are not known to infect the malaria vector Anopheles gambiae. Here we show that cifA and cifB can induce conditional sterility in the malaria vector An. gambiae. We used transgenic expression of these Wolbachia-derived genes in the An. gambiae germline to show that cifB is sufficient to cause embryonic lethality and that cifB-induced sterility is rescued by cifA expression in females. When we co-expressed cifA and cifB in male mosquitoes, the CI phenotype was attenuated. In female mosquitoes, cifB impaired fertility, which was overcome by co-expression of cifA. Our findings pave the way towards using CI to control malaria mosquito vectors., Wolbachia cifB expression in Anopheles gambiae males is sufficient to induce cytoplasmic incompatibility that is sensitive to the expression level of the factors involved.
- Published
- 2021
10. Antimalarials in mosquitoes overcome Anopheles and Plasmodium resistance to malaria control strategies
- Author
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Douglas G. Paton, Alexandra S. Probst, Erica Ma, Kelsey L. Adams, W. Robert Shaw, Naresh Singh, Selina Bopp, Sarah K. Volkman, Domombele F. S. Hien, Prislaure S. L. Paré, Rakiswendé S. Yerbanga, Abdoullaye Diabaté, Roch K. Dabiré, Thierry Lefèvre, Dyann F. Wirth, and Flaminia Catteruccia
- Subjects
Anopheles gambiae ,Anopheles ,Plasmodium falciparum ,Drug resistance ,Biology ,medicine.disease ,biology.organism_classification ,Virology ,Plasmodium ,parasitic diseases ,medicine ,Artemisinin ,Malaria ,Atovaquone ,medicine.drug - Abstract
The spread of insecticide resistance in Anopheles mosquitoes and drug resistance in Plasmodium parasites is contributing to a global resurgence of malaria, making the generation of control tools that can overcome these issues an urgent public health priority. We recently showed that the transmission of Plasmodium falciparum parasites can be efficiently blocked when exposing Anopheles gambiae females to antimalarials deposited on a treated surface, with no negative consequences on mosquito fitness. Here, we demonstrate this approach can overcome the hurdles of insecticide resistance in mosquitoes and drug resistant in parasites. We show that the transmission-blocking efficacy of mosquito-targeted antimalarials is maintained when field-derived, insecticide resistant Anopheles are exposed to the potent cytochrome b inhibitor atovaquone, demonstrating that this drug escapes insecticide resistance mechanisms that could potentially interfere with its function. Moreover, this approach prevents transmission of field-derived, artemisinin resistant P. falciparum parasites (Kelch13 C580Y mutant), proving that this strategy could be used to prevent the spread of parasite mutations that induce resistance to front-line antimalarials. Atovaquone is also highly effective at limiting parasite development when ingested by mosquitoes in sugar solutions, including in ongoing infections. These data support the use of mosquito-targeted antimalarials as a promising tool to complement and extend the efficacy of current malaria control interventions.Significance StatementEffective control of malaria is hampered by resistance to vector-targeted insecticides and parasite-targeted drugs. This situation is exacerbated by a critical lack of chemical diversity in both interventions and, as such, new interventions are badly needed. Recent laboratory studies have shown that an alternative approach based on treating Anopheles mosquitoes directly with antimalarial compounds can render the vector incapable of transmitting the Plasmodium parasites that cause malaria. While promising, showing that mosquito-targeted antimalarials remain effective against wild parasites and mosquitoes, including drug- and insecticide-resistant populations, respectively, is crucial to the future viability of this approach. In this study, carried out in the US and Burkina Faso, we show that antimalarial exposure is highly effective, even against extremely resistant mosquitoes, and can block transmission of drug-resistant parasites. By combining lab, and field-based studies in this way we have demonstrated that this novel approach can be effective in areas where conventional control measures are no longer as effective.
- Published
- 2021
11. Author Correction: Wolbachia cifB induces cytoplasmic incompatibility in the malaria mosquito vector
- Author
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Kelsey L. Adams, Daniel G. Abernathy, Bailey C. Willett, Emily K. Selland, Maurice A. Itoe, and Flaminia Catteruccia
- Subjects
Microbiology (medical) ,Immunology ,Genetics ,Cell Biology ,Applied Microbiology and Biotechnology ,Microbiology - Published
- 2022
12. Staphylococcus aureus produces pain through pore-forming toxins and neuronal TRPV1 that is silenced by QX-314
- Author
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Michael Otto, Kelsey L. Adams, Ashira Lubkin, Victor J. Torres, David Roberson, Kimbria J. Blake, Clifford J. Woolf, Tiphaine Voisin, Yuxin C. Ma, Isaac M. Chiu, Felipe A. Pinho-Ribeiro, and Pankaj Baral
- Subjects
Methicillin-Resistant Staphylococcus aureus ,0301 basic medicine ,Science ,Bacterial Toxins ,Analgesic ,TRPV1 ,Leukocidin ,Pain ,TRPV Cation Channels ,General Physics and Astronomy ,Pharmacology ,medicine.disease_cause ,Article ,General Biochemistry, Genetics and Molecular Biology ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Sodium channel blocker ,medicine ,Animals ,Anesthetics, Local ,lcsh:Science ,Pathogen ,Neurons ,Multidisciplinary ,business.industry ,fungi ,Lidocaine ,food and beverages ,General Chemistry ,Staphylococcal Infections ,Ibuprofen ,3. Good health ,Mice, Inbred C57BL ,030104 developmental biology ,Staphylococcus aureus ,Gene Knockdown Techniques ,Nociceptor ,lcsh:Q ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
The hallmark of many bacterial infections is pain. The underlying mechanisms of pain during live pathogen invasion are not well understood. Here, we elucidate key molecular mechanisms of pain produced during live methicillin-resistant Staphylococcus aureus (MRSA) infection. We show that spontaneous pain is dependent on the virulence determinant agr and bacterial pore-forming toxins (PFTs). The cation channel, TRPV1, mediated heat hyperalgesia as a distinct pain modality. Three classes of PFTs—alpha-hemolysin (Hla), phenol-soluble modulins (PSMs), and the leukocidin HlgAB—directly induced neuronal firing and produced spontaneous pain. From these mechanisms, we hypothesized that pores formed in neurons would allow entry of the membrane-impermeable sodium channel blocker QX-314 into nociceptors to silence pain during infection. QX-314 induced immediate and long-lasting blockade of pain caused by MRSA infection, significantly more than lidocaine or ibuprofen, two widely used clinical analgesic treatments., Bacterial infection can cause pain but the underlying mechanism is unclear. This study shows pain induced in mice by methicillin-resistant Staphylococcus aureus infection is mediated by bacterial pore-forming toxins, and a sodium channel blocker QX-314 can alleviate infection-associated pain.
- Published
- 2018
13. The Effect of Transient Location on the Resolution of Bistable Visual and Audiovisual Motion Sequences
- Author
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Philip M. Grove and Kelsey L Adams
- Subjects
Adult ,Male ,Bistability ,Computer science ,Speech recognition ,Motion Perception ,Inference ,Experimental and Cognitive Psychology ,Stimulus (physiology) ,050105 experimental psychology ,Coincidence ,03 medical and health sciences ,0302 clinical medicine ,Artificial Intelligence ,Humans ,0501 psychology and cognitive sciences ,Attention ,Zoom lens ,05 social sciences ,Cognition ,Response bias ,Sensory Systems ,Ophthalmology ,Space Perception ,Auditory Perception ,Female ,Percept ,030217 neurology & neurosurgery - Abstract
We examined the attention and inference accounts of audiovisual perception using the stream/bounce display, a visual stimulus wherein two identical objects move toward each other, completely superimpose, then move apart. This display has two candidate percepts: stream past each other or bounce off each other. Presented without additional visual or auditory transients, the motion sequence tends to yield the streaming percept, but when coupled with a tone or flash at the point of coincidence, the response bias flips toward bouncing. We explored two competing accounts of this effect: the attentional hypothesis and the inference hypothesis. Participants watched a series of motion sequences where a transient, when present, occurred at the moment of coincidence either colocalised with the motion sequence (congruent presentation) or on the opposite side of the display (incongruent presentation). Assuming the spotlight or zoom lens metaphor, an attentional account predicts that incongruent presentations should be associated with a higher percentage of bouncing responses than congruent presentations, while the inferential account predicts the opposite effect. No effect was found for tone-only trials. However, in trials containing a visual transient, results showed higher proportions of bounce responses within congruent over incongruent presentations, favouring the inference hypothesis over a spotlight or zoom lens attentional account.
- Published
- 2018
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