Role of Mosquito Microbiota in Reducing Malaria Transmission

Malaria is a life-threatening disease in humans causing chills, fever, and flu-like symptoms. It is caused by the parasite Plasmodium malariae, which is transmitted by the Anopheles mosquito. Following a blood meal of a human infected with P malariae, the parasite reaches sexual maturity in the mosquito, traveling through the mosquito’s gut and salivary glands.

Interestingly, the microbiota within the mosquito’s gut, salivary glands, and reproductive organs play an important role in reducing disease transmission by inhibiting Plasmodium gut colonization. This tripartite interaction—mosquito, microbiota, and Plasmodium—has attracted research attention for several decades and suggests a new approach to reducing malaria transmission.

RELATED:

• Heartworm Incidence on the Rise: What Can Veterinarians Do?
• Brazilian Monkeys Test Positive for Zika

A recent Parasite & Vectors review paper described the Anopheles microbiota, detailed its mechanisms for blocking Plasmodium infection within the mosquito, and highlighted several challenges in studying the microbiota.

Anopheles Microbiota

A developing Anopheles mosquito acquires its microbiota from its mother and external environment. Many other factors, including diet and blood-feeding history, determine the gut microbiota composition. Whether the Anopheles microbiota has a core bacterial community remains unknown, but several gram-negative bacteria families (Enterobacteriaceae, Acetobacteraceae, Flavobacteriaceae) are found within the midgut microbiota. Although the gut microbiota is very dynamic, the overall bacterial diversity of the microbiota is low.

The midgut, where blood is stored after a blood meal, “represents the first and main bottleneck of parasite development,” the authors wrote. The midgut microbiota predominantly inhibits Plasmodium, with antiparasitic activity coming mainly from gram-negative bacteria. This inhibition occurs through several mechanisms:

• Immune response: After a blood meal, rapid bacterial proliferation stimulates an antimicrobial immune response due to activation of the immune deficiency pathway.
• Anti-parasite metabolite production: The microbiota can produce reactive oxygen species, toxins, and other anti-Plasmodium metabolites. Plasmodium, however, can reportedly produce antioxidative enzymes in the gut to fight back.
• Peritrophic matrix formation: This matrix is composed of chitin and proteins that prevent Plasmodium from entering the body cavity from the midgut. Plasmodium, though, can produce chitinase in response.

Interestingly, these mechanisms may actually dampen the mosquito’s immune response against Plasmodium. For example, activation of the immunomodulatory peroxidase and dual oxidase enzymes after a blood meal helps reduce peritrophic matrix permeability, thus protecting Plasmodium from an immune response.

Regarding Plasmodium transmission, results of several studies suggest that the Anopheles gut microbiota can have a composition-dependent, negative effect on mosquito life span and population size, thus negatively affecting Plasmodium transmission.

Current Challenges

In the wild, the variability of factors influencing Anopheles microbiota composition produces highly variable microbiota diversity between individual mosquitoes. For laboratory-bred mosquitoes, differences in insectaries (eg, husbandry) can also produce variable microbiota compositions. Thus, identifying Anopheles mosquitoes with a representative microbiota is both a challenge and a need for exploring the microbiota—Plasmodium interaction.

The lack of knowledge on how nonbacterial microbiota components (viruses, fungi) interact with Plasmodium presents another challenge. Interestingly, parasites themselves may alter microbiota composition to increase their chances of successful infection.

An additional challenge is determining the role of microbiota outside the gut (salivary glands, ovaries) on Plasmodium infection and transmission. For example, salivary gland microbiota may interact with the parasite once the mosquito has become infective, possibly playing a role in parasite transmission.

Given these challenges, the authors noted that “the tripartite interaction between the mosquito, its microbiota, and the parasite is a complex relationship that still needs further investigation.”

Dr. JoAnna Pendergrass received her DVM degree from the Virginia-Maryland College of Veterinary Medicine. Following veterinary school, she completed a postdoctoral fellowship at Emory University’s Yerkes National Primate Research Center. Dr. Pendergrass is the founder and owner of JPen Communications, a medical communications company.