Tsetse flies transmit pathogenic African trypanosomes, which are the causative agents of African trypanosomiases. Current disease control strategies are aimed at controlling the size of tsetse populations, and novel strategies under development focus on reducing the ability of the flies to transmit trypanosomes. Weiss et al. stably colonized the gut of tsetse flies with the bacterium Kosakonia cowanii Zambiae (Kco_Z), which was isolated from Anopheles gambiae and has been shown to confer resistance against malaria parasites to the mosquitoes. In the presence of Kco_Z in the gut, tsetse flies were more refractory to infection with parasitic African trypanosomes compared with flies that did not harbour the bacterium. Next, the authors showed that Kco_Z acidifies the tsetse midgut, which inhibits trypanosome growth and establishment of infection. Finally, colonization of tsetse with Kco_Z conferred only a modest fitness cost to the fly, and thus this strategy could be used to reduce disease transmission.