Vector-borne agents have complex life cycles that depend on 2 different organisms, usually an insect vector, and a vertebrate host. This complexity is further compounded by the fact that many of these pathogens are zoonotic agents, meaning they can be “transmitted” from animals to humans (the most likely scenario) and vice versa. Therefore, to effectively control vector-borne diseases, we need to integrate multiple strategies. This means focusing not only on the individuals who are already sick, but also on people who are at risk of developing the disease, the animals that carry it, and the insects that spread it.

However, the implementation of such integrated strategies for the control of many vector-borne diseases, particularly the most neglected ones, may be quite challenging. Leishmaniasis, a spectrum of diseases caused by sand fly-transmitted Leishmania spp. parasites (more than 20 different species), with a total of more than 1 million estimated cases occurring per year globally, is a good example. There is only a handful of molecules we can use to treat sick individuals, most with worrisome side effects and associated with emerging resistance, and there is yet no vaccine available to protect the individuals at risk. Additionally, many reservoirs are wild animals, making reservoir control extremely challenging. Therefore, vector-targeted control assumes great importance in this context.

Most vector control strategies currently implemented in the field, including in the context of leishmaniasis, aim to reduce the contact between insects and humans. These include those that do not impact insect populations, such as the use of physical barriers (e.g. bed nets) or repellents, and those that aim to decrease insect numbers, for instance baited traps, or insecticides. Of note, the widespread use of insecticides has imposed an evolutionary pressure on insect populations, leading to the emergence of resistant insects. Interestingly, there are still no vector control strategies available that target the development of Leishmania parasites within sand flies; that, in other words, would make sand flies refractory to infection without exerting a major evolutive pressure on the insect. Our recently published article at Nature Communications (https://www.nature.com/articles/s41467-025-58769-4), addresses this limitation.

We had isolated a bacterial strain that we knew promoted the refractoriness of Anopheles mosquitoes to Plasmodium spp. infection. We knew that it could be a long shot… Other bacterial isolates known to promote mosquito refractoriness to infection, including Wolbachia and Asaia strains, were not effective as sand fly refractoriness promoting agents. Still, we decided to test it. And we are glad we did it! Overall, in our work we show that this bacterial agent not only is able to colonize the sand fly midgut, but also negatively impacts the development of Leishmania parasites within sand flies, diminishing their ability to transmit these parasites to hosts and cause disease. Of note, the fitness of colonized sand flies is not impacted, unless they are infected with Leishmania parasites. All in all, we report the first-ever potential refractoriness-promoting agent for sand flies!

Importantly, in this study, more than to try to dissect the mechanism behind our phenotype, which is likely due to both direct effects of D. tsuruhatensis TC1 excreted/secreted products on Leishmania parasites, and indirect effects of this bacterial agent via the induction of sand fly gut dysbiosis, we focused on applicability. For instance, we show that this bacterial agent works regardless of the timing of colonization (both when given before or after infection), something essential in the wild, since we don’t have a way to deliver such an agent at a specific timing of the adult sand fly life span.

We obviously also thought about translatability. To understand if a D. tsuruhatensis TC1 intervention would work in the field, we did modelling. Using real epidemiologic studies, we asked to what extent the transmission dynamics of Leishmania reported in these studies would change if we applied the parameters obtained in laboratory with D. tsuruhatensis TC1-colonized, Leishmania-infected sand flies. Long story short, our modelling revealed that the effect of D. tsuruhatensis TC1 on the sand fly infection burden, and on the sand fly infection prevalence would be enough to break Leishmania transmission cycles in the wild, disrupting the endemicity of leishmaniasis in endemic countries.

Altogether, our data strongly suggests that D. tsuruhatensis TC1 is an effective sand fly refractoriness-promoting agent that merits to be developed for implementation in the field as a vector-based strategy for the control of leishmaniasis. On its own, our data has relevant public health implications. Looking at the bigger picture, these implications may be huge. We now have an agent, D. tsuruhatensis TC1, that can potentially be used not only to disrupt the transmission of malaria by mosquitoes but also of leishmaniasis by sand flies. Of note, these diseases are co-endemic in many countries, meaning that with a single intervention, we could simultaneously control the transmission dynamics of two of the most relevant parasitic diseases worldwide. Given the significance of D. tsuruhatensis TC1 as a potential vector-based, multi vector-borne disease control intervention, we will continue to develop it toward its implementation in the field!

 Written with Janneth Rodrigues and Fabiano Oliveira.