Evaluating the Potential of Paratransgenesisas a Leishmaniasis Disease Control Strategy in the Mediterranean Basin. A Critical Review

Leishmaniasis, caused by the protozoan parasite Leishmania, impacts the lives of an estimated 700,000 people worldwide. With the geographic spread of the disease on the rise and effective treatments slow to develop, novel research into infection control is in high demand. The Mediterranean Basin is largely affected by visceral and cutaneous leishmaniasis, infecting both humans and canine reservoirs. Predictions of worsening incidence due to climate change highlight the importance of research in this region. Leishmania parasite development in the sandfly midgut indicates a potential transmission control target: the gut microbiome of the sandfly vector. The dynamic nature of the microbiome is susceptible to manipulation, allowing possible breakthroughs in preventing Leishmania transmission through paratransgenesis.Paratransgenic engineering produces transgenic bacteria that express effector molecules to inhibit parasite development and control disease transmission to human and animal reservoirs. The identification of candidate bacteria for manipulation has already begun for controlling mosquito-borne diseases. As a highly researched disease model, malaria highlights opportunities for leishmaniasis research. Combining past and current studies suggests that the microbiome, in conjunction with therapy drugs, could reduce human leishmaniasis incidence. Although promising, there are significant knowledge gaps and limitations in past research, indicating that this concept requires extensive further study.This review emphasizes the importance of basic microbiome research, which must be conducted before paratransgenesis can become a successful strategy for leishmaniasis control.