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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, which causes human African trypanosomiasis, as well as the livestock disease, nagana. Trypanosomes are spread by tsetse flies, their 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 characterized in T. brucei, co-infections with other trypanosome species (Trypanosoma congolense and Trypanosoma 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, which is dependent on the 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, which is also QS dependent. These cross-species interactions have important implications for trypanosome virulence, transmission, competition and evolution in the field.

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Fig. 1: T. congolense cell-cycle analysis reveals a reduction in proliferating cells at the peak of parasitaemia.
Fig. 2: A T. congolense orthologue of a T. brucei QS response pathway component, TbHYP2, can restore stumpy formation in a T. brucei TbHYP2 null mutant in murine infections.
Fig. 3: Treatment with TbCM or TcCM inhibits growth of pleomorphic T. brucei via QS signalling.
Fig. 4: Pleomorphic T. brucei introduced into an established T. congolense infection differentiate prematurely to stumpy forms in an effect mediated by QS signalling.


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This work was supported by a Wellcome Trust Investigator award (103740/Z/14/Z) and Royal Society Wolfson Research merit award (WM140045) to K.M. and a Biotechnology and Biological Sciences Research Council studentship to E.S. The Centre for Immunity, Infection and Evolution is supported by a Strategic Award from the Wellcome Trust (095831). We thank M. Chase-Topping for assistance with the statistical analysis, M. Waterfall for assistance with the flow cytometry and J. Matthews for comments on the manuscript.

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K.R.M. conceived and supervised the study. E.S. and K.R.M. devised the experiments. E.S. and J.Y. planned and carried out the experiments. E.S., K.R.M. and A.I. collated, analysed and interpreted the data. K.R.M. and E.S. wrote the manuscript.

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Correspondence to Keith R. Matthews.

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Silvester, E., Young, J., Ivens, A. et al. Interspecies quorum sensing in co-infections can manipulate trypanosome transmission potential. Nat Microbiol 2, 1471–1479 (2017).

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