Faced with the rapid spread of mosquitoes worldwide, and particularly the tiger mosquito in France, the use of insecticides has become widespread. An insecticide, unlike a repellent which keeps them away, is a toxic product intended to kill mosquitoes. The insecticides currently on the market are all composed of chemical molecules. Although effective at first, Many limitations are now emerging , due in part to the physiological resistance and changes in the behavior of mosquitoes, as well as the environmental damage they cause.
Today, two insecticides are exceptional and are biological insecticides based on the use of bacteria or compounds of bacterial origin:
- toxins from Bacillus thuringenesis subsp. israelensis (Bti) which are highly toxic to mosquito larvae and cause their death within days.
- infectious bacteria of the genus Wolbachia which can cause mosquito sterility and thus gradually eradicate a mosquito population.
The main advantage of biological insecticides compared to chemical insecticides is their specificity of action . They are active only against their targets, mosquitoes, and would therefore present no toxicity for humans and the environment. 1
Bti Larvicide: Toxic to Mosquito Larvae but Not So Harmless to the Environment
Bacillus thuringenesis subsp. israelensis was discovered in the 1970s. It is a bacterium naturally present in the soil, and capable of producing spores, which contain four toxins highly toxic to certain species of insects, such as mosquito larvae. 2
After ingestion of the spores, the four toxins are modified in the intestine of the larvae. They then assemble to perforate the intestinal cells, leading to the paralysis and then death of the mosquito larvae. Unlike other bacterial toxins of the same genus Bacillus , also marketed as larvicides (Btk and Bs), the mechanism of action of Bti toxins is unique* and would prevent any phenomenon of resistance or adaptation of the larvae . Bti toxins have already proven their effectiveness when sprayed in aquatic areas and are currently used, as an alternative to chemical insecticides, to control mosquito populations in several countries (Germany, Sweden, Switzerland, China and the United States). 3
However, the production costs of Bti larvicides remain high and limit their application in developing countries. In addition, the use of Bti leads to the uncontrolled eradication of all mosquito species by killing their larvae, as well as other flies. Now mosquitoes are a considerable source of food in the larval and adult stages for many species of birds and fish in particular. 4.5 So although Bti toxins specifically target mosquitoes, they have a indirect negative impact on other non-target species. French researchers have shown that the use of the larvicide Bti has disrupted an entire ecosystem in the Camargue. The drastic reduction in its mosquito population has led to a 33% decrease in the population of swallows, spiders and dragonflies and an increase in Camargue flying ants . 6.7
The Infectious Approach with Wolbachia : a bad insecticide but which would reduce the transmission of vector-borne diseases.
Wolbachia is a genus of bacteria, which can be naturally found in the gut cells of many arthropods, including mosquitoes. When infected, the female mosquito transmits the Wolbachia bacteria to her offspring. In the presence of this bacteria, mosquitoes can produce viable offspring in only 56% of crosses** . When a specific cross is imposed, this figure can drop to 0%: a male infected with Wolbachia produces no offspring with an uninfected female. 8

Wolbachia is a genus of bacteria, which can be naturally found in the gut cells of many arthropods, including mosquitoes. When infected, the female mosquito transmits the bacteria Wolbachia to his offspring. In the presence of this bacteria, mosquitoes can have viable offspring in only 56% of crosses** . When a specific cross is imposed, this figure can drop to 0%: a male infected with Wolbachia does not produce any offspring with an uninfected female. 8
Inspired by this natural phenomenon, researchers have developed a strategy, called Wolbachia IIt, by producing infected male mosquitoes in the laboratory and then releasing them into the wild so that they do not produce any offspring with wild female mosquitoes. This strategy has been widely used in the United States, China and Singapore, where it has failed. Indeed, female mosquitoes infected with Wolbachia were accidentally released, due to difficulties in sorting the sex of mosquitoes produced in the laboratory; this led to the dispersal of the bacteria in the mosquito population, cancelling out the sterility effect and without reducing the number of mosquitoes. 8
However, it would seem that the infectious approach by Wolbachia remains interesting, not as a biological insecticide to eradicate mosquitoes, as was considered for many years, but to reduce the risk of transmission of vector-borne diseases to humans. In fact, mosquitoes infected with Wolbachia transmit fewer arboviruses, such as those that cause Dengue, Zika, and Chikungunya, as well as Plasmodiums that cause Malaria, although researchers do not yet know the precise reasons for this. 8 The first attempts at dispersing Wolbachia among disease-carrying mosquito species appear conclusive, since the incidence of Dengue cases has declined sharply 5 years after the first releases of Aedes aegypti infected by Wolbachia in test regions of Australia. 9
This technology therefore seems promising for reducing the risks of infections due to mosquitoes without having to eradicate them. However, some species of mosquitoes are more difficult to produce than others, and this technology could not be applied to Anopheles gambiae , a species that carries malaria. In addition, there is still little hindsight on the stability of this technology: does the Wolbachia bacteria remain stable in mosquitoes? Does it not cause a different evolution of the infected mosquito? What about the virus or parasite carried by the mosquito? Can this lead to the creation of more virulent pathogens?
Claire Grison - Biochemistry Engineer, Doctor of Organic Chemistry and Scientific Editor
Notes:
* Bti toxins are able to interact directly with cell membrane lipids and not via transmembrane protein receptors
** Possible crosses can be numerous: uninfected female/infected male, infected female/uninfected male, infected female strain A/infected male strain B, infected female strain B/infected male strain A
References:
[1] L. Lagadic and T. Caquet, in Encyclopedia of Toxicology (Third Edition) , ed. P. Wexler, Academic Press, Oxford, 2014, pp. 355–359.
[2] Initiatory journey of an anti-mosquito toxin. | INSB, https://www.insb.cnrs.fr/fr/cnrsinfo/parcours-initiatique-dune-toxine-anti-moustique.
[3] N. Becker and P. Lüthy, in Microbial Control of Insect and Mite Pests , ed. LA Lacey, Academic Press, 2017, pp. 379–392.
[4] DAH Peach, The bizarre and ecologically important hidden lives of mosquitoes, http://theconversation.com/the-bizarre-and-ecologically-important-hidden-lives-of-mosquitoes-127599.
[5] J. Fang, Nature , 2010, 466, 432–434.
[6] B. Poulin, Acta Oecologica , 2012, 44, 28–32.
[7] B. Poulin, G. Lefebvre and L. Paz, Journal of Applied Ecology , 2010, 47, 884–889.
[8] G.-H. Wang, S. Gamez, RR Raban, JM Marshall, L. Alphey, M. Li, JL Rasgon and OS Akbari, Nat Commun , 2021, 12, 4388.
[9] PA Ryan, AP Turley, G. Wilson, TP Hurst, K. Retzki, J. Brown-Kenyon, L. Hodgson, N. Kenny, H. Cook, BL Montgomery, CJ Paton, SA Ritchie, AA Hoffmann, NP Jewell, SK Tanamas, KL Anders, CP Simmons and SL O'Neill, Gates Open Res , 2019, 3, 1547.