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

Abstract

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.

A Leap Into the Unknown – Early Events in African Trypanosome Transmission

“…Nonetheless, mitochondrial activity is greater in T. congolense and T. vivax bloodstream forms than in T. brucei slender forms [76], and evidence suggests that T. congolense has a different strategy to T. brucei to prepare for transmission. Thus, T. congolense parasites accumulate in G1/G0 of the cell cycle [77], similar to T. brucei and T. vivax [78], but gene expression changes accompanying the transition from ascending to peak parasitemia in T. congolense do not mirror the slender-to-stumpy transition in T. brucei [79]. Indeed, T. congolense transcripts upregulated at peak parasitemia frequently belong to T. congolense-specific groups, such as surface phylome family 22 members [79].…”

Extracellular Vesicles Could Carry an Evolutionary Footprint in Interkingdom Communication

“…In infections caused by protozoan parasites, the release of EVs can be observed throughout most of the parasite's life cycle, suggesting that EVs are a fundamental component of parasitic infection. As previously reported, EVs are involved in the host-parasite interaction and in communication between parasites, inducing dysfunction in the immune responses or manipulating the physiology and metabolism of the host (Silvester et al, 2017). EVs have been identified in some of the most pathogenic protozoans, those responsible for some of the most widespread, lethal and disabling vector-borne diseases, such as Chagas disease, African trypanosomiasis, and leishmaniasis.…”

Infections With Extracellular Trypanosomes Require Control by Efficient Innate Immune Mechanisms and Can Result in the Destruction of the Mammalian Humoral Immune System

“…The results of combined experiments showed the systems are indeed similar as the T. congolense genes can complement the pathway in T. brucei. In addition, conditioned culture medium from T. congolense promotes stumpy formation of T. brucei in vitro, and T. congolense co-infection accelerates differentiation to stumpy forms in T. brucei (47).…”