TY - JOUR A1 - Schuster, Sarah A1 - Lisack, Jaime A1 - Subota, Ines A1 - Zimmermann, Henriette A1 - Reuter, Christian A1 - Mueller, Tobias A1 - Morriswood, Brooke A1 - Engstler, Markus T1 - Unexpected plasiticty in the life cycle of Trypanosoma brucei JF - eLife N2 - African trypanosomes cause sleeping sickness in humans and nagana in cattle. These unicellular parasites are transmitted by the bloodsucking tsetse fly. In the mammalian host’s circulation, proliferating slender stage cells differentiate into cell cycle-arrested stumpy stage cells when they reach high population densities. This stage transition is thought to fulfil two main functions: first, it auto-regulates the parasite load in the host; second, the stumpy stage is regarded as the only stage capable of successful vector transmission. Here, we show that proliferating slender stage trypanosomes express the mRNA and protein of a known stumpy stage marker, complete the complex life cycle in the fly as successfully as the stumpy stage, and require only a single parasite for productive infection. These findings suggest a reassessment of the traditional view of the trypanosome life cycle. They may also provide a solution to a long-lasting paradox, namely the successful transmission of parasites in chronic infections, despite low parasitemia. KW - trypanosoma KW - sleeping sickness KW - tsetse fly KW - transmission KW - life cycle KW - development Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-261744 VL - 10 ER - TY - JOUR A1 - Reuter, Christian A1 - Hauf, Laura A1 - Imdahl, Fabian A1 - Sen, Rituparno A1 - Vafadarnejad, Ehsan A1 - Fey, Philipp A1 - Finger, Tamara A1 - Jones, Nicola G. A1 - Walles, Heike A1 - Barquist, Lars A1 - Saliba, Antoine-Emmanuel A1 - Groeber-Becker, Florian A1 - Engstler, Markus T1 - Vector-borne Trypanosoma brucei parasites develop in artificial human skin and persist as skin tissue forms JF - Nature Communications N2 - Transmission of Trypanosoma brucei by tsetse flies involves the deposition of the cell cycle-arrested metacyclic life cycle stage into mammalian skin at the site of the fly’s bite. We introduce an advanced human skin equivalent and use tsetse flies to naturally infect the skin with trypanosomes. We detail the chronological order of the parasites’ development in the skin by single-cell RNA sequencing and find a rapid activation of metacyclic trypanosomes and differentiation to proliferative parasites. Here we show that after the establishment of a proliferative population, the parasites enter a reversible quiescent state characterized by slow replication and a strongly reduced metabolism. We term these quiescent trypanosomes skin tissue forms, a parasite population that may play an important role in maintaining the infection over long time periods and in asymptomatic infected individuals. KW - mechanisms of disease KW - parasitology KW - transcriptomics Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-358142 VL - 14 ER -