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Tsetse flies ( Glossina  spp.) vector pathogenic trypanosomes ( Trypanosoma  spp.) in sub-Saharan Africa. These parasites cause human and animal African trypanosomiases, which are debilitating diseases that inflict an enormous socio-economic burden on inhabitants of endemic regions. Current disease control strategies rely primarily on treating infected animals and reducing tsetse population densities. However, relevant programs are costly, labor intensive and difficult to sustain. As such, novel strategies aimed at reducing tsetse vector competence require development. Herein we investigated whether  Kosakonia cowanii  Zambiae ( Kco_Z ), which confers  Anopheles gambiae  with resistance to  Plasmodium , is able to colonize tsetse and induce a trypanosome refractory phenotype in the fly.  Kco_Z  established stable infections in tsetse’s gut and exhibited no adverse effect on the fly’s survival. Flies with established  Kco_Z  infections in their gut were significantly more refractory to infection with two distinct trypanosome species ( T .  congolense , 6% infection;  T .  brucei , 32% infection) than were age-matched flies that did not house the exogenous bacterium ( T .  congolense , 36% infected;  T .  brucei , 70% infected). Additionally, 52% of  Kco_Z  colonized tsetse survived infection with entomopathogenic  Serratia  marcescens, compared with only 9% of their wild-type counterparts. These parasite and pathogen refractory phenotypes result from the fact that  Kco_Z  acidifies tsetse’s midgut environment, which inhibits trypanosome and  Serratia  growth and thus infection establishment. Finally, we determined that  Kco_Z  infection does not impact the fecundity of male or female tsetse, nor the ability of male flies to compete with their wild-type counterparts for mates. We propose that  Kco_Z  could be used as one component of an integrated strategy aimed at reducing the ability of tsetse to transmit pathogenic trypanosomes.

Colonization of the tsetse fly midgut with commensal Kosakonia cowanii Zambiae inhibits trypanosome infection establishment