Wolbachia pipientis is an α-proteobacterium endosymbiont, an intracellular gram-negative bacteria, which was first identified in 1924 by Hertig and Wolbach1,2. These microbes are widespread among nematodes and arthropods. They are predominantly transmitted vertically from mother to the offsprings but also occasionally transmitted horizontally between species. In doing so, they infect a huge range of arthropod species worldwide. It is estimated that the proportion of W. pipientis-infected arthropod species is around 40%, indicating that Wolbachia is the most abundant endosymbionts among Arthropoda3.
The most unique ability of W. pipientis is that once it infects a host, it manipulates the reproductive system of the infected host. Hosts infected with W. pipientis regulate its reproduction by producing females only without fertilization by sperm, feminizing infected males into females, and killing male embryos which increases the rate of infected females. The most representative effect of W. pipientis is Cytoplasmic Incompatibility(CI). Simply put, when infected males cross uninfected females, they result in embryo death, and in more complex CIs, crossings between males and females infected with different W. pipientis strains, result in reciprocally bidirectional incompatibility. Their uniqueness in altering the reproduction has led many scientists to test the possibility of using W. pipientis to control pests and pathogens4.
In 2011, a study that brought this potential use of W. pipientis to reality was carried out in Australia to effectively prevent dengue fever, which is transmitted through mosquitoes5,6. Dengue fever is a major viral disease that is widespread throughout the tropics, and there are no vaccines or treatments available today. Traditional methods such as pesticides have been used to inhibit the main transmission vector, the mosquito Aedes aegypti, but it hasn’t been very successful. Now that W. pipientis is able to be spread among wild mosquitoes and disrupt the dengue transmission cycle, the tool has attracted the attention of relevant researchers.
Using the cellular incompatibility method described earlier, W. pipientis was able to spread quickly through the uninfected mosquitoes. The mother-to-progeny strain causes uninfected females to cross with infected males, which causes eggs to die and rapidly invade insect host populations by inducing only the progeny of infected females to thrive. Not only this, an interesting feature of W. pipientis is the prevention of dengue viruses from replicating in the tissues of mosquitoes. Because the virus cannot replicate, it cannot transmit the dengue virus to humans and the disease is not spread. It has already been shown that W. pipientis prevents the growth of the Drosophila C virus from other studies. The Australian research team repeated the same experiment several times and found the virus suppression results were consistent.
There were concerns with the release of mosquitoes infected with W. pipientis into the world as it has no detrimental effect on the community. The team found that W. pipientis is too large to penetrate through the mosquito’s salivary glands and thus cannot be passed to humans. For three years, volunteers tracked people who were bitten by mosquitoes infected with W. pipientis and showed they are not able to observe related microbial infections in humans. In fact, as W. pipientis is already infected with many arthropods in nature, including mosquitoes, it is considered these risks are low. Before the first W. pipientis mosquitoes were released in 2011, an independent risk assessment was commissioned by the Australian National Scientific Research Institute, CSIRO. A team of experts scrutinized the community’s awareness of changes in mosquito density, the possibility of dengue fever, and the risks associated with dengue fever. We carefully examined the challenges, including changes. CSIRO’s final report concluded that the release of W. pipientis mosquitoes would represent the lowest level of risk that could be ignored by people and the environment.
The study of W. pipientis is conducted around the world and the approaches vary7. A study published in 2019 showed that W. pipientis was used to nearly exterminate white lined mosquitoes in two islands in Guangzhou, China, where the highest rates of dengue infections exist8. This is due to the bidirectional cellular inconsistency, which is one of the characteristics of W. pipientis. After spraying mosquitoes infected with W. pipientis, the adult population of wild-type females decreased 83% in 2016 and 94% in 2017.
The accomplishments with the use of W. pipientis and the attempts of applying W. pipientis to dengue fever as well as yellow fever and Zika virus continues. In the future, it will be ideal to conduct this study on a more extensive scale, leading to effective public health strategies.
References
- 1.Hertig M, Wolbach S. Studies on Rickettsia-Like Micro-Organisms in Insects. J Med Res. 1924;44(3):329-374.7. https://www.ncbi.nlm.nih.gov/pubmed/19972605.
- 2.Hertig M. The Rickettsia, Wolbachia pipientis (gen. et sp.n.) and Associated Inclusions of the Mosquito, Culex pipiens. Parasitology. October 1936:453-486. doi:10.1017/s0031182000022666
- 3.Zug R, Hammerstein P. Still a Host of Hosts for Wolbachia: Analysis of Recent Data Suggests That 40% of Terrestrial Arthropod Species Are Infected. Cordaux R, ed. PLoS ONE. June 2012:e38544. doi:10.1371/journal.pone.0038544
- 4.Stouthamer R, Breeuwer JAJ, Hurst GDD. Wolbachia Pipientis: Microbial Manipulator of Arthropod Reproduction. Annu Rev Microbiol. October 1999:71-102. doi:10.1146/annurev.micro.53.1.71
- 5.Hoffmann AA, Montgomery BL, Popovici J, et al. Successful establishment of Wolbachia in Aedes populations to suppress dengue transmission. Nature. August 2011:454-457. doi:10.1038/nature10356
- 6.O’Neill Scott. How a Tiny Bacterium Called Wolbachia Could Defeat Dengue. SCIENTIFIC AMERICAN. https://www.scientificamerican.com/article/how-a-tiny-bacterium-called-wolbachia-could-defeat-dengue/. Published June 1, 2015.
- 7.WORLD MOSQUITO PROGRAM. . https://www.worldmosquitoprogram.org/.
- 8.Zheng X, Zhang D, Li Y, et al. Incompatible and sterile insect techniques combined eliminate mosquitoes. Nature. July 2019:56-61. doi:10.1038/s41586-019-1407-9