- Author: Kathy Keatley Garvey
Alarm bells went off. Scientists joined forces to target the mosquito and stop it from spreading throughout the state.
Enter the UC Davis laboratory of medical entomologist-geneticist Geoffrey Attardo, associate professor, UC Davis Department of Entomology and Nematology.
And now, enter the exit seminar of doctoral candidate Erin "Taylor" Kelly of the Attardo lab.
She'll present a seminar on "Investigating the Metabolic Underpinnings of Pyrethroid Resistance in California Aedes aegypti" at 3:30 p.m., Thursday, June 8 in 366 Briggs Hall and also on Zoom.
"The world's primary arboviral vector, Aedes aegypti, was reintroduced into California in 2013," Kelly says in her abstract. "Its re-establishment throughout the state appears to be due, in part, to the failure of pyrethroid insecticides applied for adult mosquito control. My dissertation work examines 1) population dynamics within the state 2) how mosquito metabolism is impacted by pyrethroid exposure and 3) how a pyrethroid susceptible reference strain of Aedes aegypti differs physiologically from a wild California Ae. aegypti population. This research describes a successful story of ˆexclusion and generated novel hypotheses about the physiological underpinnings of the fitness costs and tradeoffs observed in insects withthepyrethroid resistance phenotype. Additionally, I explore novel targets for insecticide synergism."
UC Davis medical entomologist Anthony Cornel, who leads the Mosquito Control Research Laboratory in Parlier, works with Taylor on insecticide resistance in mosquitoes. “Taylor's PhD project is challenging as she endeavors to tease apart the biochemical and genetic factors that cause resistance to some commonly used insecticides to control Aedes aegypti," wrote Cornel, a member of the UC Davis Department of Entomology and Nematology faculty. "Ae. aegypti is considered the second most dangerous insect worldwide because of its role in transmission of dengue, yellow fever, Zika and Chikungunya viruses which cause considerable morbidity and mortality. Hence, it is an important organism to study especially to eventually improve measures to control this mosquito."
Active in leadership activities and the Entomological Society of America, Kelly is president of the Entomology Graduate Student Association (EGSA), and served two terms as president of the UC Davis Equity in STEM and Entrepreneurship (ESTEME). She was a member of the UC Davis team that won the national Entomology Games championship in 2022. The UC Davis team included three other doctoral candidates from the Department of Entomology and Nematology: Zachary Griebenow of the Phil Ward lab, captain; Jill Oberski of the Ward laboratory; and Madison “Madi” Hendrick of the Ian Grettenberger lab. The event is a lively question-and-answer, college bowl-style competition on entomological facts played between university-sponsored student teams. The question categories include biological control, behavior and ecology, economic and applied entomology, medical, urban and veterinary entomology, morphology and physiology, biochemistry and toxicology, systematics and evolution integrated pest management and insect/plant interactions.
Other highlights of her years pursuing a doctorate at UC Davis include:
- She was selected the recipient of the 2022 Student Leadership Award from the Pacific Branch of ESA, which encompasses 11 Western states, parts of Canada and Mexico and several U.S. territories. (See news story)
- She won a first-place award at the 2021 Entomological Society of America (ESA) meeting with her poster, “Metabolic Snapshot: Using Metabolomics to Compare Near-Wild and Colonized Aedes aegypti.”
Kelly, who joined the Attardo lab in 2018, holds a bachelor of science degree in biology, with a minor in chemistry, from Santa Clara University, where she served as president of the campuswide Biology Club and led STEM projects, encouraging and guiding underrepresented students to seek careers in science, technology, engineering and mathematics (STEM).
Her future plans? "I'm pursuing vector ecologist positions within California vector control programs!"
(Editor's Note: For the Zoom password, contact associate professor Geoffrey Attardo at gmattardo@ucdavis.edu or Taylor Kelly at etkelly@ucdavis.edu.)
/span>- Author: Kathy Keatley Garvey
"We are working with scientists and public health authorities in STP to establish the conditions that would facilitate an informed societal and government decision about a proposed release of Anopheles mosquitoes engineered to prevent transmission of the malaria parasite Plasmodium falciparum on the islands,” said principal investigator Gregory Lanzaro, director of the Vector Genetics Laboratory and a PMI professor.
This award will be used to extend their ongoing entomological, engagement and capacity building work through 2025.
“We are working in collaboration with the UC Irvine Malaria Initiative (UCIMI), a research consortium including scientists from UC Irvine, San Diego and Berkeley as well as Johns Hopkins University,” Lanzaro said. “We are working toward the application of advanced genetic tools aimed at the mosquito vector. It is our belief that this approach, used in conjunction with early malaria treatment and detection, can provide a cost effective, sustainable, and environmentally responsible program to ultimately eliminate malaria from Africa.”
Said Ana Kormos, engagement program manager and lead author of the proposal: “These funds provide the UCIMI program with support to strengthen our existing relationship-based approach to the co-development of this technology and ensures that our partners in STP lead the decision-making processes involved in all aspects of the research. This is a huge step forward in advancing a truly collaborative approach to translational research.”
The Vector Genetics Laboratory is engaged in research and training in the areas of population and molecular genetics, genomics and bioinformatics of insect vectors of human and animal disease. The website: “We have developed a program aimed at expanding knowledge that may be applied to improving control of disease vectors and that also addresses problems of interest in the field of evolutionary genetics. We are currently engaged in a range of projects, but our major research focus is on vectors of malaria in Africa."
Directors of the Vector Genetics Laboratory research programs are Lanzaro and Anthony "Anton" Cornel, a research entomologist with the UC Davis Department of Entomology and Nematology and director of the Mosquito Control Research Laboratory, Parlier.
New Tools. "The fight to reduce and possibly eliminate malaria continues and becomes especially challenging as efforts to reduce malaria morbidity have plateaued since 2015,” said Cornel. “Therefore, we must seriously consider new tools. One such tool is genetically modifying the major mosquito vector in the Afrotropics so that it cannot transmit malaria."
"The project aims to use genetically modified (GM) mosquito strategy to reduce and eliminate malaria from the Islands of São Tomé and Príncipe, as proof of concept, before using this technology on larger scales on mainland Africa,” Cornel said, adding that his role, as a field team co-investigator for UCIMI and VGL, is to work with Lanzaro and Pinto “to understand as much as we can about the behavior, population structure and population sizes of Anopheles coluzzi (the malaria vector) on these islands to design the most efficient strategy of releasing the genetically modified mosquitoes to have maximum effect.”
Malaria is an acute illness caused by Plasmodium parasites, which spread to humans through the bites of infected female Anopheles mosquitoes, according to the World Health Organization (WHO). In 2020, nearly half of the world's population was at risk of malaria. An estimated 241 million cases of malaria occurred worldwide in 2020, with 627,000 dying.
Tremendous Burden. Medical entomologist and geneticist Geoffrey Attardo of the UC Davis Department of Entomology and Nematology (who is not involved in this project), noted that “Malaria is a disease which creates a tremendous burden on people living in affected areas. In particular its impacts on the mortality in young children and pregnant women are devastating. Attempts to control this disease using traditional methods have been effective in recent years.”
The island nation of São Tomé and Príncipe, population of 178,700 in 2016, is located about 200 miles west of Gabon on Africa's mainland. It shares maritime borders with Equatorial Guinea, Gabon, and Nigeria. The combined area of the archipelago is about five times the size of Washington, DC. The United States established diplomatic relations with São Tomé and Príncipe in 1976, following its independence from Portugal.
Open Philanthropy's mission, as noted on its website, is to “give as effectively as we can and share our findings openly so that anyone can build on our work. Through research and grant-making, we hope to learn how to make philanthropy go especially far in terms of improving lives. We're passionate about maximizing the impact of our giving, and we're excited to connect with other donors who share our passion.”
Resource:
São Tomé and Príncipe (nationsonline.org)
- Author: Kathy Keatley Garvey
The species has now reached at least 17 California counties and its successful spread may be linked to its resistance to pyrethroids, according to newly published UC Davis research examining genetic markers of resistance at five state locations.
The work, published in the current edition of Parasites & Vectors, a BioMed Central open-access medical journal, focuses on “determining how informative well-established genetic markers of resistance to pyrethroids are in predicting the resistance phenotype of individual mosquitoes of Aedes aegypti within a population,” said Attardo, the lead author.
“Specifically, we generated mosquito colonies from invasive A. aegypti populations from four locations in the Central Valley (Dinuba, Clovis, Sanger and Kingsburg) and from collections in the Greater Los Angeles Area,” he said. “Mosquitoes from these populations have all demonstrated resistance to pyrethroid-type insecticides and we think this may be part of the reason why these mosquitoes have been so successful in spreading throughout California.”
A. aegypti transmits such viruses as dengue, Zika, chikungunya, and yellow fever. Despite California's aggressive surveillance and treatment efforts, this species presents a “significant challenge to local control agencies,” the nine-member team wrote in their research paper, “Frequency of Sodium Channel Genotypes and Association with Pyrethrum Knockdown Time in Populations of Californian Aedes aegypti.“
The paper is online and publicly accessible at https://bit.ly/3vmUxXR.
“What was interesting was that while all the mosquitoes from California show resistance to pyrethroids, there is a lot of variability from one individual to the next in terms of the level of resistance, even when they are carrying genetically identical resistance mutations,” Attardo said. “In particular, there seem to be two levels of resistance in these populations. The two levels seem to represent a resistant group and a super resistant group. However, the proportions of resistant/super-resistant differ in the sampled mosquitoes from population to population.”
Of particular interest was that mosquitoes carrying the resistance mutations at all five genetic locations were very resistant, he said. “However, there was also a large amount of unexplained variability in terms of the knockdown phenotypes demonstrated by mosquitoes of the same age and rearing conditions. We compared the knockdown times of mosquitoes positive for all five resistance mutations from different populations and found that these mutations account for only a proportion of the observed level of resistance. We believe that the unexplained variability is likely being mediated by the presence or absence of an undefined resistance mechanism.”
Although A. aegypti was first detected in California in 2013, researchers believe that its arrival involved multiple introductions. Populations in Southern California are thought to have crossed the border from Mexico, while Central Valley populations may have been introduced, in part, from the southeastern United States.
“Upon detection in 2013, the Consolidated Mosquito Abatement District implemented an integrated vector control management strategy which involved extensive public education, thorough property inspections, sanitation, insecticide treatment at larval sources and residual barrier spraying with pyrethroids,” the authors wrote. Despite their efforts, the species successfully overwintered and continued to spread, implicating that it arrived in California with genetic mutations “conferring resistance to the type I pyrethroid insecticides applied for vector control in California.”
The co-authors include former UC Davis mosquito researcher Yoosook Lee, now at the University of Florida-Florida Medical Entomology Laboratory, Vero Beach; research entomologist Anthony Cornel and staff research associate Katherine Brisco of the Mosquito Control Research Laboratory, Kearney Agriculture and Extension Center and UC Davis Department of Entomology and Nematology; and Lindsey Mack, Erin Taylor Kelly, Katherine Brisco, Kaiyuan Victoria Shen, Aamina Zahid, and Tess van Schoor, all with the UC Davis Department of Entomology and Nematology.
For more information and photos, see news story on "UC Davis Researches Examine Pyrethroid Reistance in Spread of Aedes aegypti," on the UC Davis Department of Entomology and Nematology's website.
- Author: Kathy Keatley Garvey
The work, published in the current edition of Parasites & Vectors, a BioMed Central open-access medical journal, focuses on “determining how informative well-established genetic markers of resistance to pyrethroids are in predicting the resistance phenotype of individual mosquitoes of Aedes aegypti within a population,” said lead author Geoffrey Attardo, medical entomologist-geneticist in the UC Davis Department of Entomology and Nematology.
“Specifically, we generated mosquito colonies from invasive A. aegypti populations from four locations in the Central Valley (Dinuba, Clovis, Sanger and Kingsburg) and from collections in the Greater Los Angeles Area,” he said. “Mosquitoes from these populations have all demonstrated resistance to pyrethroid-type insecticides and we think this may be part of the reason why these mosquitoes have been so successful in spreading throughout California.”
A. aegypti transmits such viruses as dengue, Zika, chikungunya, and yellow fever. Despite California's aggressive surveillance and treatment efforts, this species presents a “significant challenge to local control agencies,” the nine-member team wrote in their research paper, “Frequency of Sodium Channel Genotypes and Association with Pyrethrum Knockdown Time in Populations of Californian Aedes aegypti.“
The paper is online and publicly accessible at https://bit.ly/3vmUxXR.
“What was interesting was that while all the mosquitoes from California show resistance to pyrethroids, there is a lot of variability from one individual to the next in terms of the level of resistance, even when they are carrying genetically identical resistance mutations,” Attardo said. “In particular, there seem to be two levels of resistance in these populations. The two levels seem to represent a resistant group and a super resistant group. However, the proportions of resistant/super-resistant differ in the sampled mosquitoes from population to population.”
Of particular interest was that mosquitoes carrying the resistance mutations at all five genetic locations were very resistant, he said. “However, there was also a large amount of unexplained variability in terms of the knockdown phenotypes demonstrated by mosquitoes of the same age and rearing conditions. We compared the knockdown times of mosquitoes positive for all five resistance mutations from different populations and found that these mutations account for only a proportion of the observed level of resistance. We believe that the unexplained variability is likely being mediated by the presence or absence of an undefined resistance mechanism.”
In launching the project, the researchers designed an assay “to test for the presence of mutations in the gene coding for the pyrethroid target protein, the voltage gated sodium channel (the para gene),” Attardo explained. “Detection of these mutations is used to monitor the level or resistance in populations. However, the actual link between the effect the genotype has on the phenotype of individual mosquitoes has not been looked at in detail. “
The scientists identified mutations from genetic sequences of Californian mosquitoes provided by co-author Yoosook Lee, a former UC Davis mosquito researcher now at the University of Florida-Florida Medical Entomology Laboratory, Vero Beach.
The authors also include research entomologist Anthony Cornel and staff research associate Katherine Brisco of the Mosquito Control Research Laboratory, Kearney Agriculture and Extension Center and UC Davis Department of Entomology and Nematology; and Lindsey Mack, Erin Taylor Kelly, Katherine Brisco, Kaiyuan Victoria Shen, Aamina Zahid, and Tess van Schoor, all with the UC Davis Department of Entomology and Nematology.
First, they tested the individual resistance phenotype of mosquitoes by placing them into bottles coated with the pyrethroid insecticide permethrin, and observed them to determine how long it takes for them to respond to the insecticide. Said Attardo: “This is a modified version of the assay used by the Center for Disease Control and Prevention to evaluate phenotypic resistance in groups of mosquitoes.”
Then they isolated the DNA from and performed a high-throughput genetic analysis on each individual to determine the composition of the five mutations in each individual. Next they looked at the resulting data to see how well knockdown time correlates with individual genotypes of mosquitoes.
Although A. aegypti was first detected in California in 2013, researchers believe that its arrival involved multiple introductions. Populations in Southern California are thought to have crossed the border from Mexico, while Central Valley populations may have been introduced, in part, from the southeastern United States.
“Upon detection in 2013, the Consolidated Mosquito Abatement District implemented an integrated vector control management strategy which involved extensive public education, thorough property inspections, sanitation, insecticide treatment at larval sources and residual barrier spraying with pyrethroids,” the authors wrote. Despite their efforts, the species successfully overwintered and continued to spread, implicating that it arrived in California with genetic mutations “conferring resistance to the type I pyrethroid insecticides applied for vector control in California.”
The project drew financial support from the Pacific Southwest Regional Center of Excellence for Vector-Borne Diseases, funded by the U.S. Centers for Disease Control and Prevention.
- Author: Kathy Keatley Garvey
And well it should.
Research led by UC Davis medical entomologists and published in the Sept. 15 edition of PLOS Genetics, indicates "a genetic component" to the blood-feeding behavior and host choice of Anopheles arabiensis.
The research was done in Kilombero Valley in Tanzania.
"We know that blood feeding preference among mosquitoes can be species specific,” said co-author and professor Greg Lanzaro, who leads the Vector Genetics Laboratory, UC Davis Department of Pathology, Microbiology and Immunology and is an affiliate of the UC Davis Department of Entomology and Nematology. “For example, there are mosquito species that specialize in feeding on amphibians or reptiles. We also know that many species are more catholic when choosing a meal and this can have important implications to human health—it's how some disease agents move between animals and humans.”
The publication, titled "The Genetic Basis of Host Preference and Resting Behavior in the Major African Malaria Vector, Anopheles arabiensis, is the work of a 13-member international team.
Medical entomologist and co-author Anthony Cornel of the UC Davis Department of Entomology and Nematology faculty--his lab is based at the Kearney Agricultural Research and Extension Center in Parlier--had this to say about the significance of the research: "From my perspective I would state that environmental anthropogenic influences by replacing natural habitats for human dwelling, need for more food and water by creating more agricultural lands and changing local water patterns, increasing domestic animal rangeland and use of insecticides can have quite dramatic influences of disease vector behavior and their genetic diversity. These changes should be monitored in the overall context of how these mosquito adaptations influence disease transmission dynamics.”
Other co-authors are researchers Yoosook Lee, Heather Ferguson, Travis Collier, Catelyn Nieman, Allison Weakley, all of the Vector Genetics Lab; Katharina Kreppel, Nicodem Govella and Anicet Kihonda of the Ifakara Health Institute, Ifakara, United Republic of Tanzania; and computer scientists Eleazar Eskin and Eun Yong Kang of UCLA.
Their summary?
“Malaria transmission is driven by the propensity for mosquito vectors to bite people, while its control depends on the tendency of mosquitoes to bite and rest in places where they will come into contact with insecticides. In many parts of Africa, where coverage with Long Lasting Insecticide Treated Nets is high, Anopheles arabiensis is the only remaining malaria vector. We sought to assess the potential for An. arabiensis to adapt its behavior to avoid control measures by investigating the genetic basis for its host choice and resting behavior. Blood-fed An. arabiensis were collected resting indoors and outdoors in the Kilombero Valley, Tanzania. We sequenced a total of 48 genomes representing 4 phenotypes (human or cow fed, resting in or outdoors) and tested for genetic associations with each phenotype. Genomic analysis followed up by application of a novel molecular karyotyping assay which revealed a relationship between An. arabiensis that fed on cattle and the standard arrangement of the 3Ra inversion. This is strong support that An. arabiensis blood-feeding behavior has a substantial genetic component. Controlled host choice assays are needed to confirm a direct link between allelic variation within the 3Ra inversion and host preference.”
You can read the paper online in PLOS Genetics.