Discovered more than a century ago in mosquitoes, the bacterial genus Wolbachia is one of the most common parasitic microbes of insects. The bacteria reside in the cytoplasm of host cells and modify their reproductive capabilities, often resulting in sterility. Over the past 100 years, this endosymbiont has captivated researchers’ interest, both due to its interaction with its host and because of its applications in controlling disease vectors.
Dive in to revisit the endosymbiont’s journey, right from its discovery to how researchers leverage it to control vector-borne viruses like dengue, target the obligate bacteria inside parasitic filarial worms, and engage citizen scientists globally to map its vast biological distribution.
A Century of Wolbachia: From Discovery to Controlling Diseases
In the early 1900s, entomologist Marshall Hertig and pathologist Simeon Burt Wolbach brought mosquitoes to their lab to characterize the microbes they harbored. Dissecting insect tissues and examining them under the microscope revealed bacteria in their ovaries, testes, and eggs. Over time, the researchers found these endosymbionts in a number of insect species and identified that infected female insects passed Wolbachia to their offspring. Digging deeper, researchers discovered that Wolbachia manipulated its host reproductive success, turning the bacterium into an unlikely ally in the fight against pathogens.
Wolbachia (red) are known to infect the oocytes (blue and green) of insects such as Drosophila melanogaster.
Yonah Radousky
Wolbitos Help Control Disease Vectors in the Field
A few years ago, vector biologist Luciano Moreira joined forces with University of Queensland biologist and founder and chief executive officer of the World Mosquito Program Scott O’Neill to leverage Wolbachia as a biocontrol agent against mosquito-borne pathogens. Building on previous work indicating that Wolbachia could induce resistance to viral pathogens in their hosts, the duo infected Aedes aegypti mosquitoes with the endosymbiont and exposed them to dengue and chikungunya viruses. Compared to uninfected mosquitoes, Wolbachia-infected mosquitoes had lower levels of viral genetic materials. These insects also had an impaired ability to obtain blood meals, which could reduce their disease transmitting ability. Encouraged by this, Moreira pioneered the use of Wolbachia-infected mosquitoes, later nicknamed “wolbitos,” to control disease spread in Brazil as part of the World Mosquito Program there.
Wolbachia as Filarial Worms’ Achilles Heel
When Institute for Advanced Biosciences chemist Andrés Palencia was developing therapies to target roundworms that cause lymphatic filariasis, a devastating parasitic disease, he knew he needed to get creative. He turned to knowledge from the 1970s, when scientists discovered that microscopic roundworms that spread the disease depend on Wolbachia for their growth and survival. Palencia and his team leveraged this to develop a drug that inhibits Wolbachia’s growth, disrupting its symbiosis with its nematode host and highlighting how targeting a pathogen’s microbiome could be a promising approach to control infections in humans.
Researchers are producing Wolbachia-infected A. aegypti mosquitoes as a strategy to control the spread of dengue virus in many locations around the world.
Flavio Carvalho, World Mosquito Program Brazil
An Animal Biotechnologist Uses Sterile Insect Technique to Control Disease-Causing Vectors
As part of her PhD research, Asha Wijegunawardana, now an animal biotechnologist at the Rajarata University of Sri Lanka, studied population control methods for mosquitoes carrying the dengue virus. She explored both sterilization of male mosquitoes and infecting female insects with Wolbachia, which blocks the insects’ ability to carry the virus. Screening native mosquito species revealed that the majority did not carry Wolbachia, offering a promising approach to leverage this endosymbiont to control dengue virus-transmitting vectors. Her team also uses genetic modification approaches to reduce the reproductive and pathogen-spreading abilities of other insects such as sandflies, which spread the parasite that causes leishmaniasis.
Wolbachia Brings Citizen Scientists Together
Nearly 20 years ago, Pennsylvania State University biologist Seth Bordenstein and his colleagues launched a citizen science project called Discover the Microbes Within! The Wolbachia Project. The goal was to screen insects and help researchers identify new hosts that harbor Wolbachia, which had been challenging given that nearly half of the seven million insect species on Earth carry the Wolbachia endosymbiont. Citizen scientists collect and identify insects, carrying out PCR using reagents and equipment provided by the program to investigate whether the arthropods harbor Wolbachia. They can also send the samples for sequencing. Through this project, participants have assessed the presence of Wolbachia in 1,500 insect species and shared their findings in the project’s user database.
How Wolbachia-Infected Mosquitoes Prevent Dengue Virus Replication
While researchers established that Wolbachia-infected mosquitoes act as biocontrol agents to keep dengue at bay, they did not completely understand the underlying mechanism. Robson Loterio, a microbiologist at the Burnet Institute sought to find out. Subjecting Wolbachia-infected mosquitoes to microscopy revealed that the endosymbionts largely clustered near the host cells’ endoplasmic reticulum. Since this organelle produces molecules used in lipid synthesis, the researchers dug deeper and found that Wolbachia infection—which prevented dengue viral replication—led to lipid accumulation in cells. Inhibiting this lipid buildup allowed dengue virus replication, indicating that Wolbachia’s antiviral mechanism relies on excess lipid aggregation.
Releasing Millions of Mosquitoes to Help Curb West Nile Virus
As part of the Google Debug project, researchers infected West Nile virus-spreading male mosquitoes with a strain of Wolbachia that renders its host sterile. When these mosquitoes mate with an uninfected female mosquito, the mating is incompatible and the eggs do not hatch. By combining automated rearing systems and AI-driven approaches to sort males from females, the Debug project strategy aims to release only Wolbachia-carrying male mosquitoes, which is safer for people since male mosquitoes do not bite.
