Interspecies quorum-sensing in co-infections can manipulate trypanosome transmission potential

Quorum sensing (QS) is commonly used in microbial communities and some unicellular parasites to coordinate group behaviours1,2. An example is Trypanosoma brucei that causes Human African trypanosomiasis, as well as the livestock disease, nagana. Trypanosomes are spread by tsetse flies, transmission being enabled by cell-cycle arrested ‘stumpy forms’ that are generated in a density-dependent manner in mammalian blood. QS is mediated through a small (<500 Da), non-proteinaceous, stable but unidentified ‘stumpy induction factor’3, whose signal response pathway has been identified. Although QS is characterised in T. brucei, co-infections with other trypanosome species (T. congolense, T. vivax) are common in animals, generating the potential for interspecies interactions. Here, we show that T. congolense exhibits density-dependent growth control in vivo and conserves QS-regulatory genes, of which one can complement a T. brucei QS signal-blind mutant to restore stumpy formation. Thereafter we demonstrate that T. congolense-conditioned culture medium promotes T. brucei stumpy formation in vitro, dependent upon integrity of the QS signalling pathway. Finally, we show that, in vivo, co-infection with T. congolense accelerates differentiation to stumpy forms in T. brucei, this also being QS dependent. These cross-species interactions have important implications for trypanosome virulence, transmission, competition and evolution in the field.