scholarly journals Bacterial Toxins Active against Mosquitoes: Mode of Action and Resistance

Toxins ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 523
Author(s):  
Maria Helena Neves Lobo Silva-Filha ◽  
Tatiany Patricia Romão ◽  
Tatiana Maria Teodoro Rezende ◽  
Karine da Silva Carvalho ◽  
Heverly Suzany Gouveia de Menezes ◽  
...  

Larvicides based on the bacteria Bacillus thuringiensis svar. israelensis (Bti) and Lysinibacillus sphaericus are effective and environmentally safe compounds for the control of dipteran insects of medical importance. They produce crystals that display specific and potent insecticidal activity against larvae. Bti crystals are composed of multiple protoxins: three from the three-domain Cry type family, which bind to different cell receptors in the midgut, and one cytolytic (Cyt1Aa) protoxin that can insert itself into the cell membrane and act as surrogate receptor of the Cry toxins. Together, those toxins display a complex mode of action that shows a low risk of resistance selection. L. sphaericus crystals contain one major binary toxin that display an outstanding persistence in field conditions, which is superior to Bti. However, the action of the Bin toxin based on its interaction with a single receptor is vulnerable for resistance selection in insects. In this review we present the most recent data on the mode of action and synergism of these toxins, resistance issues, and examples of their use worldwide. Data reported in recent years improved our understanding of the mechanism of action of these toxins, showed that their combined use can enhance their activity and counteract resistance, and reinforced their relevance for mosquito control programs in the future years.

2021 ◽  
Vol 2 ◽  
Author(s):  
Anastasia Accoti ◽  
Cecilia Springer Engdahl ◽  
George Dimopoulos

The increased application of chemical control programs has led to the emergence and spread of insecticide resistance in mosquitoes. Novel environmentally safe control strategies are currently needed for the control of disease vectors. The use of entomopathogenic fungi could be a suitable alternative to chemical insecticides. Currently, Beauveria spp. and Metarhizium spp. are the most widely used entomopathogenic fungi for mosquito control, but increasing the arsenal with additional fungi is necessary to mitigate the emergence of resistance. Entomopathogenic fungi are distributed in a wide range of habitats. We have performed a comprehensive screen for candidate mosquitocidal fungi from diverse outdoor environments in Maryland and Puerto Rico. An initial screening of 22 fungi involving exposure of adult Anopheles gambiae to 2-weeks-old fungal cultures identified five potent pathogenic fungi, one of which is unidentified and the remaining four belonging to the three genera Galactomyces sp., Isaria sp. and Mucor sp. These fungi were then screened against Aedes aegypti, revealing Isaria sp. as a potent mosquito killer. The entomopathogenic effects were confirmed through spore-dipping assays. We also probed further into the killing mechanisms of these fungi and investigated whether the mosquitocidal activities were the result of potential toxic fungus-produced metabolites. Preliminary assays involving the exposure of mosquitoes to sterile filtered fungal liquid cultures showed that Galactomyces sp., Isaria sp. and the unidentified isolate 1 were the strongest producers of factors showing lethality against An. gambiae. We have identified five fungi that was pathogenic for An. gambiae and one for Ae. aegypti, among these fungi, four of them (two strains of Galactomyces sp., Mucor sp., and the unidentified isolate 1) have never previously been described as lethal to insects. Further characterization of these entomopathogenic fungi and their metabolites needs to be done to confirm their potential use in biologic control against mosquitoes.


2020 ◽  
Vol 86 (7) ◽  
Author(s):  
Nathaly Alexandre Nascimento ◽  
Mary Carmen Torres-Quintero ◽  
Samira López Molina ◽  
Sabino Pacheco ◽  
Tatiany Patrícia Romão ◽  
...  

ABSTRACT The binary (Bin) toxin from Lysinibacillus sphaericus is effective to mosquito larvae, but its utilization is threatened by the development of insect resistance. Bin toxin is composed of the BinB subunit required for binding to midgut receptors and the BinA subunit that causes toxicity after cell internalization, mediated by BinB. Culex quinquefasciatus resistance to this toxin is caused by mutations that prevent expression of Bin toxin receptors in the midgut. Previously, it was shown that the Cyt1Aa toxin from Bacillus thuringiensis subsp. israelensis restores Bin toxicity to Bin-resistant C. quinquefasciatus and to Aedes aegypti larvae, which are naturally devoid of functional Bin receptors. Our goal was to elucidate the mechanism involved in Cyt1Aa synergism with Bin in such larvae. In vivo assays showed that the mixture of Bin toxin, or its BinA subunit, with Cyt1Aa was effective to kill resistant larvae. However, no specific binding interaction between Cyt1Aa and the Bin toxin, or its subunits, was observed. The synergy between Cyt1Aa and Bin toxins is dependent on functional Cyt1Aa, as demonstrated by using the nontoxic Cyt1AaV122E mutant toxin affected in oligomerization and membrane insertion, which was unable to synergize Bin toxicity in resistant larvae. The synergism correlated with the internalization of Bin or BinA into anterior and medium midgut epithelial cells, which occurred only in larvae treated with wild-type Cyt1Aa toxin. This toxin is able to overcome failures in the binding step involving BinB receptor by allowing the internalization of Bin toxin, or its BinA subunit, into the midgut cells. IMPORTANCE One promising management strategy for mosquito control is the utilization of a mixture of L. sphaericus and B. thuringiensis subsp. israelensis insecticidal toxins. From this set, Bin and Cyt1Aa toxins synergize and display toxicity to resistant C. quinquefasciatus and to A. aegypti larvae, whose midgut cells lack Bin toxin receptors. Our data set provides evidence that functional Cyt1Aa is essential for internalization of Bin or its BinA subunit into such cells, but binding interaction between Bin and Cyt1Aa is not observed. Thus, this mechanism contrasts with that for the synergy between Cyt1Aa and the B. thuringiensis subsp. israelensis Cry toxins, where active Cyt1Aa is not necessary but a specific binding between Cry and Cyt1Aa is required. Our study established the initial molecular basis of the synergy between Bin and Cyt1Aa, and these findings enlarge our knowledge of their mode of action, which could help to develop improved strategies to cope with insect resistance.


2020 ◽  
Vol 227 ◽  
pp. 103918
Author(s):  
Muhammad Asam Riaz ◽  
Michael J. Adang ◽  
Gang Hua ◽  
Tatiana Maria Teodoro Rezende ◽  
Antonio Mauro Rezende ◽  
...  

Toxins ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 288
Author(s):  
Simab Kanwal ◽  
Shalini Abeysinghe ◽  
Monrudee Srisaisup ◽  
Panadda Boonserm

Binary toxin (Bin toxin), BinA and BinB, produced by Lysinibacillus sphaericus has been used as a mosquito-control agent due to its high toxicity against the mosquito larvae. The crystal structures of Bin toxin and non-insecticidal but cytotoxic parasporin-2 toxin share some common structural features with those of the aerolysin-like toxin family, thus suggesting a common mechanism of pore formation of these toxins. Here we explored the possible cytotoxicity of Bin proteins (BinA, BinB and BinA + BinB) against Hs68 and HepG2 cell lines. The cytotoxicity of Bin proteins was evaluated using the trypan blue exclusion assay, MTT assay, morphological analysis and LDH efflux assay. The intracellular localization of Bin toxin in HepG2 cells was assessed by confocal laser scanning microscope. HepG2 cells treated with BinA and BinB (50 µg/mL) showed modified cell morphological features and reduced cell viability. Bin toxin showed no toxicity against Hs68 cells. The EC50 values against HepG2 at 24 h were 24 ng/mL for PS2 and 46.56 and 39.72 µg/mL for BinA and BinB, respectively. The induction of apoptosis in treated HepG2 cells was confirmed by upregulation of caspase levels. The results indicated that BinB mediates the translocation of BinA in HepG2 cells and subsequently associates with mitochondria. The study supports the possible development of Bin toxin as either an anticancer agent or a selective delivery vehicle of anticancer agents to target mitochondria of human cancer cells in the future.


Pathogens ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1251
Author(s):  
Keshava Mysore ◽  
Longhua Sun ◽  
Limb K. Hapairai ◽  
Chien-Wei Wang ◽  
Joseph B. Roethele ◽  
...  

Prevention of mosquito-borne infectious diseases will require new classes of environmentally safe insecticides and novel mosquito control technologies. Saccharomyces cerevisiae was engineered to express short hairpin RNA (shRNA) corresponding to mosquito Rbfox1 genes. The yeast induced target gene silencing, resulting in larval death that was observed in both laboratory and outdoor semi-field trials conducted on Aedes aegypti. High levels of mortality were also observed during simulated field trials in which adult females consumed yeast delivered through a sugar bait. Mortality correlated with defects in the mosquito brain, in which a role for Rbfox1 as a positive regulator of Notch signaling was identified. The larvicidal and adulticidal activities of the yeast were subsequently confirmed in trials conducted on Aedes albopictus, Anopheles gambiae, and Culex quinquefasciatus, yet the yeast had no impact on survival of select non-target arthropods. These studies indicate that yeast RNAi pesticides targeting Rbfox1 could be further developed as broad-based mosquito larvicides and adulticides for deployment in integrated biorational mosquito control programs. These findings also suggest that the species-specificity of attractive targeted sugar baits, a new paradigm for vector control, could potentially be enhanced through RNAi technology, and specifically through the use of yeast-based interfering RNA pesticides.


Pathogens ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 947
Author(s):  
Rishi Kondapaneni ◽  
Ashley N. Malcolm ◽  
Brian M. Vazquez ◽  
Eric Zeng ◽  
Tse-Yu Chen ◽  
...  

Florida lies within a subtropical region where the climate allows diverse mosquito species including invasive species to thrive year-round. As of 2021, there are currently 66 state-approved Florida Mosquito Control Districts, which are major stakeholders for Florida public universities engaged in mosquito research. Florida is one of the few states with extensive organized mosquito control programs. The Florida State Government and Florida Mosquito Control Districts have long histories of collaboration with research institutions. During fall 2020, we carried out a survey to collect baseline data on the current control priorities from Florida Mosquito Control Districts relating to (1) priority control species, (2) common adult and larval control methods, and (3) major research questions to address that will improve their control and surveillance programs. The survey data showed that a total of 17 distinct mosquito species were considered to be priority control targets, with many of these species being understudied. The most common control approaches included truck-mounted ultra-low-volume adulticiding and biopesticide-based larviciding. The districts held interest in diverse research questions, with many prioritizing studies on basic science questions to help develop evidence-based control strategies. Our data highlight the fact that mosquito control approaches and priorities differ greatly between districts and provide an important point of comparison for other regions investing in mosquito control, particularly those with similar ecological settings, and great diversity of potential mosquito vectors, such as in Florida. Our findings highlight a need for greater alignment of research priorities between mosquito control and mosquito research. In particular, we note a need to prioritize filling knowledge gaps relating to understudied mosquito species that have been implicated in arbovirus transmission.


Insects ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 71
Author(s):  
Tse-Yu Chen ◽  
Chelsea T. Smartt ◽  
Dongyoung Shin

Aedes aegypti, as one of the vectors transmitting several arboviruses, is the main target in mosquito control programs. Permethrin is used to control mosquitoes and Aedes aegypti get exposed due to its overuse and are now resistant. The increasing percentage of permethrin resistant Aedes aegypti has become an important issue around the world and the potential influence on vectorial capacity needs to be studied. Here we selected a permethrin resistant (p-s) Aedes aegypti population from a wild Florida population and confirmed the resistance ratio to its parental population. We used allele-specific PCR genotyping of the V1016I and F1534C sites in the sodium channel gene to map mutations responsible for the resistance. Two important factors, survival rate and vector competence, that impact vectorial capacity were checked. Results indicated the p-s population had 20 times more resistance to permethrin based on LD50 compared to the parental population. In the genotyping study, the p-s population had more homozygous mutations in both mutant sites of the sodium channel gene. The p-s adults survived longer and had a higher dissemination rate for dengue virus than the parental population. These results suggest that highly permethrin resistant Aedes aegypti populations might affect the vectorial capacity, moreover, resistance increased the survival time and vector competence, which should be of concern in areas where permethrin is applied.


2019 ◽  
Vol 57 (3) ◽  
pp. 957-961
Author(s):  
Kyran M Staunton ◽  
Barukh B Rohde ◽  
Michael Townsend ◽  
Jianyi Liu ◽  
Mark Desnoyer ◽  
...  

Abstract Aedes aegypti (Linnaeus), the primary vectors of the arboviruses dengue virus and Zika virus, continue to expand their global distributions. In efforts to better control such species, several mosquito control programs are investigating the efficacy of rearing and releasing millions of altered male Aedes throughout landscapes to reduce populations and disease transmission risk. Unfortunately, little is known about Ae. aegypti, especially male, dispersal behaviors within urban habitats. We deployed Sound-producing Gravid Aedes Traps (SGATs) in Cairns, northern Australia, to investigate male Ae. aegypti attraction to various oviposition container configurations. The traps were arranged to include: 1) water only, 2) organically infused water, 3) infused water and L3 larvae, 4) infused water and a human-scented lure, and lastly 5) no water or olfactory attractant (dry). Our data suggest that males were more attracted to SGATs representing active larval sites than potential larval sites, but were equally attracted to dry SGATs relative to those containing water and/or infusion. Additionally, we found that female Ae. aegypti were equally attracted to wet SGATs, with or without infusion, but not dry ones. These results suggest that male Ae. aegypti within northern Australia are more attracted to active larval sites and equally attracted to dry containers as wet or infused ones. Additionally, female Ae. aegypti are unlikely to enter dry containers. Such findings contribute to our understanding of potentially attractive features for local and released Ae. aegypti throughout the northern Australian urban landscape.


Health Policy ◽  
2007 ◽  
Vol 83 (2-3) ◽  
pp. 196-212 ◽  
Author(s):  
Daniel E. Impoinvil ◽  
Sajjad Ahmad ◽  
Adriana Troyo ◽  
Joseph Keating ◽  
Andrew K. Githeko ◽  
...  

2018 ◽  
Vol 6 (1) ◽  
pp. 52-62 ◽  
Author(s):  
Roopa Rani Samal ◽  
Sarita Kumar

Background: Mosquito control is a major concern throughout the world because of rising cases of mosquito-borne diseases. The outbreak of Zika, Dengue and Chikungunya has caused grave situations raising urgent need to control Aedes aegypti. Moreover, extensive use of synthetic insecticides in mosquito control programs has resulted in high levels of insecticide resistance leading to the use of magnified concentrations, impacting human health and environment adversely. The knowledge about current status of the insecticide susceptibility against Ae. aegypti could help to devise mosquito control strategy. Objective: Present study evaluates the larvicidal potential of thirteen insecticides belonging to seven different classes; organochlorines, organophosphates, carbamates, pyrethroids, neonicotinoids, avermectins and secondary metabolites; against early fourth instars of Ae. aegypti. Materials and Methods: The insecticide susceptibility was evaluated as per WHO protocol. Fatality counts were made after 24h of exposure; and the LC50, LC90 and other statistical parameters were computed by probit-regression analysis. Results: The data reveals the maximum efficacy of pyrethroids and fenitrothion, with lethal values less than 0.001 ppm. Avermectins, organochlorines and carbamates were moderately toxic, while neonicotinoid posed appreciable toxicity. In contrast, berberine, a secondary plant metabolite was found inefficient. The larvicidal efficacy of tested insecticides against Ae. aegypti was found in the decreasing order of pyrethroids > organophosphates > avermectins > organochlorines > carbamates > neonicotinoids > secondary metabolites. Conclusion: Present investigations explore various toxicants as Dengue vector control agents in order to devise a suitable control strategy for mosquito control in fields.


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