An infectious duo: The slender – stumpy success story

Abstract text

The unicellular protozoan Trypanosoma brucei brucei, together with T. vivax and T. congolense, causes Animal African Trypanosomiasis (AAT) in livestock and wildlife in sub-Saharan Africa. These diseases are accompanied by a high degree of economic damage, affecting the low-income population severely. Since the parasite has a digenetic life cycle, the mammalian host is not the only organism it infects. Much of the T. brucei life cycle takes place in the arthropod vector, the tsetse fly (Glossina spp.). There are two forms of T. brucei in the circulation of an infected animal: the slender and stumpy bloodstream forms (bsf). The slender form proliferates, while the stumpy form is cell cycle-arrested. It is common knowledge that the stumpy forms rapidly differentiate to the first insect stage once being ingested by the tsetse fly. For more than a century it was assumed that the slender bsf dies in the tsetse midgut. It was only in 2021 that we showed that the slender bsf are perfectly capable of infecting the tsetse fly and going through the entire life cycle. Since quantitative experiments with vector infections are extremely complex, the question remained whether stumpy and slender forms are actually equally effective in colonising the tsetse fly. Therefore, we performed co-infection experiments with two differently fluorescent cell lines of T. brucei, one of which as slender form, the other as stumpy. These experiments were accompanied by in vitro analyses of the developmental transition of slender and stumpy trypanosomes to the insect stage using RNA-Seq. Furthermore, we tested if age of the flies makes a difference. It is thought that tsetse flies are less likely to get infected the older they become. Hence, infections of either slender or stumpy bsf were done with flies after their second or third feed. Altogether, we show that slender and stumpy bsf are equally successful in infecting the vector and going through the entire life cycle. In this process, slender forms do not become stumpy, but turn on specific genes to directly become the first insect stage (procyclic) in the midgut of the fly. Preliminary results also indicate that slender bsf, along with stumpy bsf, can also infect non-teneral flies. It can now be said without a doubt that the slender bsf of T. brucei are also able to infect the tsetse fly vector.