scholarly journals Barcoded Asaia bacteria enable mosquito in vivo screens and identify novel systemic insecticides and inhibitors of malaria transmission

PLoS Biology ◽  
2021 ◽  
Vol 19 (12) ◽  
pp. e3001426
Author(s):  
Angelika Sturm ◽  
Martijn W. Vos ◽  
Rob Henderson ◽  
Maarten Eldering ◽  
Karin M. J. Koolen ◽  
...  
Keyword(s):  
Small Molecules ◽  
Recombinant Dna ◽  
Blood Feeding ◽  
Microtiter Plate ◽  
Parasite Development ◽  
Mosquito Vector ◽  
Vector Borne Diseases ◽  
Systemic Insecticides ◽  
Vector Borne

This work addresses the need for new chemical matter in product development for control of pest insects and vector-borne diseases. We present a barcoding strategy that enables phenotypic screens of blood-feeding insects against small molecules in microtiter plate-based arrays and apply this to discovery of novel systemic insecticides and compounds that block malaria parasite development in the mosquito vector. Encoding of the blood meals was achieved through recombinant DNA-tagged Asaia bacteria that successfully colonised Aedes and Anopheles mosquitoes. An arrayed screen of a collection of pesticides showed that chemical classes of avermectins, phenylpyrazoles, and neonicotinoids were enriched for compounds with systemic adulticide activity against Anopheles. Using a luminescent Plasmodium falciparum reporter strain, barcoded screens identified 48 drug-like transmission-blocking compounds from a 400-compound antimicrobial library. The approach significantly increases the throughput in phenotypic screening campaigns using adult insects and identifies novel candidate small molecules for disease control.

scholarly journals The use of barcoded Asaia bacteria in mosquito in vivo screens for identification of systemic insecticides and inhibitors of malaria transmission

2021 ◽  
Author(s):  
Sturm Angelika ◽  
Martijn Vos ◽  
Rob Henderson ◽  
Maarten Eldering ◽  
Karin Koolen ◽  
...  
Keyword(s):  
Small Molecules ◽  
Recombinant Dna ◽  
Blood Feeding ◽  
Microtiter Plate ◽  
Parasite Development ◽  
Mosquito Vector ◽  
Vector Borne Diseases ◽  
Anopheles Mosquitoes ◽  
Systemic Insecticides

This work addresses the need for new chemical matter in product development for control of pest insects and vector-borne diseases. We present a barcoding strategy that enables phenotypic screens of blood-feeding insects against small molecules in microtiter plate-based arrays and apply this to discovery of novel systemic insecticides and compounds that block malaria parasite development in the mosquito vector. Encoding of the bloodmeals was achieved through recombinant DNA-tagged Asaia bacteria that successfully colonized Aedes and Anopheles mosquitoes. An arrayed screen of a collection of pesticides showed that chemical classes of avermectins, phenylpyrazoles and neonicotinoids were enriched for compounds with systemic adulticide activity against Anopheles. Using a luminescent Plasmodium falciparum reporter strain, barcoded screens identified 48 drug-like transmission blocking compounds from a 400-compound antimicrobial library. The approach significantly increases the throughput in phenotypic screening campaigns using adult insects, and identifies novel candidate small molecules for disease control.

scholarly journals Inhibition of Plasmodium Liver Infection by Ivermectin

2016 ◽  
Vol 61 (2) ◽  
Author(s):  
António M. Mendes ◽  
Inês S. Albuquerque ◽  
Marta Machado ◽  
Joana Pissarra ◽  
Patrícia Meireles ◽  
...  
Keyword(s):  
Control Strategies ◽  
Parasite Development ◽  
Mammalian Host ◽  
Mosquito Vector ◽  
Content Type ◽  
Vector Borne Diseases ◽  
Host Infection ◽  
Liver Infection

ABSTRACT Avermectins are powerful endectocides with an established potential to reduce the incidence of vector-borne diseases. Here, we show that several avermectins inhibit the hepatic stage of Plasmodium infection in vitro. Notably, ivermectin potently inhibits liver infection in vivo by impairing parasite development inside hepatocytes. This impairment has a clear impact on the ensuing blood stage parasitemia, reducing disease severity and enhancing host survival. Ivermectin has been proposed as a tool to control malaria transmission because of its effects on the mosquito vector. Our study extends the effect of ivermectin to the early stages of mammalian host infection and supports the inclusion of this multipurpose drug in malaria control strategies.

Global Warming and Vector-borne Infectious Diseases

2008 ◽  
Vol 3 (2) ◽  
pp. 105-112 ◽  
Author(s):  
Mutsuo Kobayashi ◽  
◽  
Osamu Komagata ◽  
Naoko Nihei
Keyword(s):  
Global Warming ◽  
Infectious Diseases ◽  
Heat Waves ◽  
Blood Feeding ◽  
Mosquito Vector ◽  
Vector Borne Diseases ◽  
Extreme Climate ◽  
Ipcc Report ◽  
Vector Borne ◽  
Global Mean Sea Level

Vector-borne diseases result from infections transmitted to humans by blood-feeding arthropods such as mosquitoes, ticks, and fleas. Such cold-blooded animals are influenced by environmental change. A recent IPCC report clearly showed that the emission of greenhouse gases has already changed world climates. Heat waves in Europe, rises in global mean sea level, summer droughts and wild fires, more intense precipitation, and increasing numbers of large cyclones and hurricanes may be typical example of extreme climate phenomena related to global warming. High temperatures may increase survival among arthropods, depending on their vector, behavior, ecology, and valuable factors, and temperate zone warming may accelerate the spread of mosquitoes such asAedes albopictus. The MIROK (K1) Model clearly shows a northern limit forAe.albopictus, particularly in northern Honshu in 2035 and southern and middle Hokkaido Island in 2100 in Japan. The spread of the mosquito vector through global used-tire trading in recent decades to Africa, the Mideast, Europe, and North and South America caused an outbreak of Chikungunya fever in north Italy in 2007. Global warming, extreme climate change, changing physical distribution, and an increase in oversea travel are also expected to influence the epidemiology of vector-borne infectious diseases.

Current Challenges in the Development of Vaccines and Drugs Against Emerging Vector-borne Diseases

2019 ◽  
Vol 26 (16) ◽  
pp. 2974-2986 ◽  
Author(s):  
Kwang-sun Kim
Keyword(s):  
New Host ◽  
In Vivo Models ◽  
Vector Borne Diseases ◽  
Novel Drugs ◽  
Huge Impact ◽  
Tick Borne Disease ◽  
Vector Borne ◽  
Living Organisms

Vectors are living organisms that transmit infectious diseases from an infected animal to humans or another animal. Biological vectors such as mosquitoes, ticks, and sand flies carry pathogens that multiply within their bodies prior to delivery to a new host. The increased prevalence of Vector-Borne Diseases (VBDs) such as Aedes-borne dengue, Chikungunya (CHIKV), Zika (ZIKV), malaria, Tick-Borne Disease (TBD), and scrub typhus has a huge impact on the health of both humans and livestock worldwide. In particular, zoonotic diseases transmitted by mosquitoes and ticks place a considerable burden on public health. Vaccines, drugs, and vector control methods have been developed to prevent and treat VBDs and have prevented millions of deaths. However, development of such strategies is falling behind the rapid emergence of VBDs. Therefore, a comprehensive approach to fighting VBDs must be considered immediately. In this review, I focus on the challenges posed by emerging outbreaks of VBDs and discuss available drugs and vaccines designed to overcome this burden. Research into promising drugs needs to be upgraded and fast-tracked, and novel drugs or vaccines being tested in in vitro and in vivo models need to be moved into human clinical trials. Active preventive tactics, as well as new and upgraded diagnostics, surveillance, treatments, and vaccination strategies, need to be monitored constantly if we are to manage VBDs of medical importance.

scholarly journals Drug Resistance in Filarial Parasites Does Not Affect Mosquito Vectorial Capacity

Pathogens ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 2
Author(s):  
Erik Neff ◽  
Christopher C. Evans ◽  
Pablo D. Jimenez Castro ◽  
Ray M. Kaplan ◽  
Guha Dharmarajan
Keyword(s):  
Drug Resistance ◽  
Transmission Efficiency ◽  
Vectorial Capacity ◽  
Vertebrate Host ◽  
Mosquito Vector ◽  
Drug Resistant ◽  
Vector Borne Diseases ◽  
Asian Tiger ◽  
Significant Difference ◽  
Vector Borne

Parasite drug resistance presents a major obstacle to controlling and eliminating vector-borne diseases affecting humans and animals. While vector-borne disease dynamics are affected by factors related to parasite, vertebrate host and vector, research on drug resistance in filarial parasites has primarily focused on the parasite and vertebrate host, rather than the mosquito. However, we expect that the physiological costs associated with drug resistance would reduce the fitness of drug-resistant vs. drug-susceptible parasites in the mosquito wherein parasites are not exposed to drugs. Here we test this hypothesis using four isolates of the dog heartworm (Dirofilaria immitis)—two drug susceptible and two drug resistant—and two vectors—the yellow fever mosquito (Aedes aegypti) and the Asian tiger mosquito (Ae. albopictus)—as our model system. Our data indicated that while vector species had a significant effect on vectorial capacity, there was no significant difference in the vectorial capacity of mosquitoes infected with drug-resistant vs. drug-susceptible parasites. Consequently, contrary to expectations, our data indicate that drug resistance in D. immitis does not appear to reduce the transmission efficiency of these parasites, and thus the spread of drug-resistant parasites in the vertebrate population is unlikely to be mitigated by reduced fitness in the mosquito vector.

scholarly journals Time to Micromanage the Pathogen-Host-Vector Interface: Considerations for Vaccine Development

Vaccines ◽  
2019 ◽  
Vol 7 (1) ◽  
pp. 10 ◽  
Author(s):  
Jessica E. Manning ◽  
Tineke Cantaert
Keyword(s):  
Vaccine Development ◽  
Blood Feeding ◽  
Adaptive Responses ◽  
Host Pathogen Interactions ◽  
Current Increase ◽  
Vector Borne Diseases ◽  
Vector Borne Disease ◽  
Host Pathogen ◽  
Added Benefit ◽  
Vector Borne

The current increase in vector-borne disease worldwide necessitates novel approaches to vaccine development targeted to pathogens delivered by blood-feeding arthropod vectors into the host skin. A concept that is gaining traction in recent years is the contribution of the vector or vector-derived components, like salivary proteins, to host-pathogen interactions. Indeed, the triad of vector-host-pathogen interactions in the skin microenvironment can influence host innate and adaptive responses alike, providing an advantage to the pathogen to establish infection. A better understanding of this “bite site” microenvironment, along with how host and vector local microbiomes immunomodulate responses to pathogens, is required for future vaccines for vector-borne diseases. Microneedle administration of such vaccines may more closely mimic vector deposition of pathogen and saliva into the skin with the added benefit of near painless vaccine delivery. Focusing on the ‘micro’–from microenvironments to microbiomes to microneedles–may yield an improved generation of vector-borne disease vaccines in today’s increasingly complex world.

Investigation on the virologic vector-borne diseases by mosquito vector in Yeongnam, Korea

2011 ◽  
Vol 41 (6) ◽  
pp. 286-286
Author(s):  
Heeju Hwang ◽  
SeWon Kang ◽  
ByungUn No ◽  
Dongkyu Lee ◽  
WookGyo Lee ◽  
...  
Keyword(s):  
Mosquito Vector ◽  
Vector Borne Diseases ◽  
Vector Borne

scholarly journals Modulating CRISPR gene drive activity through nucleocytoplasmic localization of Cas9 in S. cerevisiae

2018 ◽  
Author(s):  
Megan E. Goeckel ◽  
Erianna M. Basgall ◽  
Isabel C. Lewis ◽  
Samantha C. Goetting ◽  
Yao Yan ◽  
...  
Keyword(s):  
Nuclease Activity ◽  
Gene Drive ◽  
Wild Populations ◽  
Vector Borne Diseases ◽  
Vector Borne ◽  
Mendelian Laws ◽  
Artificial Gene ◽  
Nuclear Localization Sequences ◽  
Gene Drives

ABSTRACTThe bacterial CRISPR/Cas genome editing system has provided a major breakthrough in molecular biology. One use of this technology is within a nuclease-based gene drive. This type of system can install a genetic element within a population at unnatural rates. Combatting of vector-borne diseases carried by metazoans could benefit from a delivery system that bypasses traditional Mendelian laws of segregation. Recently, laboratory studies in fungi, insects, and even mice, have demonstrated successful propagation of CRISPR gene drives and the potential utility of this type of mechanism. However, current gene drives still face challenges including evolved resistance, containment, and the consequences of application in wild populations. In this study, we use an artificial gene drive system in budding yeast to explore mechanisms to modulate nuclease activity of Cas9 through its nucleocytoplasmic localization. We examine non-native nuclear localization sequences on Cas9 fusion proteins in vivo and demonstrate that appended signals can titrate gene drive activity and serve as a potential molecular safeguard.

scholarly journals Borrelia infection in rodent host has dramatic effects on the microbiome of ticks

2021 ◽  
Author(s):  
Phineas T. Hamilton ◽  
Elodie Maluenda ◽  
Anouk Sarr ◽  
Alessandro Belli ◽  
Georgia Hurry ◽  
...  
Keyword(s):  
Large Scale ◽  
Vector Competence ◽  
Bacterial Community Composition ◽  
Blood Feeding ◽  
Rodent Host ◽  
Vector Borne Diseases ◽  
Bacterial Microbiome ◽  
Vector Borne ◽  
Scale Experiment ◽  
Tick Microbiome

AbstractBackgroundVector-borne diseases remain major causes of human morbidity and mortality. It is increasingly recognized that the community of microbes inhabiting arthropods can strongly affect their vector competence, but the role of the tick microbiome in Borrelia transmission – the cause of Lyme disease – remains unclear.ResultsHere, we use a large-scale experiment to clarify the reciprocal interactions between Borrelia afzelii and the microbiome of Ixodes ricinus, its primary vector. In contrast to other reports, we find that depletion of the bacterial microbiome in larval ticks has no effect on their subsequent acquisition of B. afzelii during blood feeding on infected mice. Rather, exposure to B. afzelii-infected hosts drives pervasive changes to the tick microbiome, decreasing overall bacterial abundance, shifting bacterial community composition, and increasing bacterial diversity. These effects appear to be independent of the acquisition of B. afzelii by ticks, suggesting they are mediated by physiological or immunological aspects of B. afzelii infection in the rodent host.ConclusionsManipulation of the microbiome of I. ricinus larvae had no effect on their ability to acquire B. afzelii. In contrast, B. afzelii infection in the mouse had dramatic effects on the composition of the gut microbiome in I. ricinus nymphs. Our study demonstrates that vector-borne infections in the vertebrate host shape the microbiome of the arthropod vector.

Community Perception Regarding Mosquito-Borne Diseases in Some Selected Areas of Ganjam District of Odisha State, India

2021 ◽  
pp. 0272684X2110049
Author(s):  
Sisir K Nayak ◽  
Surya N Swain ◽  
T Sarita Achari ◽  
Tapan K Barik
Keyword(s):  
Disease Incidence ◽  
Basic Knowledge ◽  
Health Concern ◽  
Mosquito Vector ◽  
College Level ◽  
Community Perception ◽  
Vector Borne Diseases ◽  
Vector Population ◽  
Vector Borne ◽  
Ganjam District

Mosquito-borne diseases are a major public health concern. Because of absence of effective therapy and vaccination to treat and prevent such vector-borne diseases, these initial cases have triggered strong concerns within medical communities, turning a bad dream into reality. To date, reducing the mosquito vector population remains the main strategy to control the transmission of mosquito borne diseases. In this connection, community-based perception recognized as an essential tool for long-term vector control management. In this study, a community perception survey was carried out in six selected study areas of Ganjam district of Odisha. A total of 3257 inhabitants from randomly chosen 600 no. of houses from 06 selected study areas were interviewed using a pre-tested structured questionnaire about various mosquito vector-borne diseases. As an outcome, we found that only 36% of people have basic knowledge and idea about vector-borne diseases, out of which only 14% know Anopheles as a causative agent whereas Aedes and Culex were very least concern. Regarding the source of knowledge, electronic media was the principal source of information, while the involvements of health personnel were least mentioned. Results of the current study indicates the necessity to plan health education program to bring important perceptions regarding vector-borne diseases at school and college level because the infrequent source of knowledge is the main cause of an increase in the disease incidence.

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