Unexpected plasticity in the life cycle of Trypanosoma brucei
- University of Würzburg, Germany
- University of Wuerzburg, Germany
Abstract
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.
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Funding
Deutsche Forschungsgemeinschaft (EN305)
- Markus Engstler
Deutsche Forschungsgemeinschaft (SPP1726)
- Markus Engstler
German-Israeli Foundation for Scientific Research and Development (ant I-473-416.13/2018)
- Markus Engstler
Deutsche Forschungsgemeinschaft (GRK2157)
- Markus Engstler
Deutsche Forschungsgemeinschaft (396187369)
- Brooke Morriswood
Bundesministerium für Bildung und Forschung (NUM Organostrat)
- Markus Engstler
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2021, Schuster et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Unexpected plasticity in the life cycle of Trypanosoma brucei
eLife 10:e66028.
https://doi.org/10.7554/eLife.66028
Further reading
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- Microbiology and Infectious Disease
The parasite that causes African sleeping sickness can be transmitted from mammals to tsetse flies in two stages of its lifecycle, rather than one as was previously thought.
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- Immunology and Inflammation
- Microbiology and Infectious Disease
Pseudomonas aeruginosa (PA) is an opportunistic, frequently multidrug-resistant pathogen that can cause severe infections in hospitalized patients. Antibodies against the PA virulence factor, PcrV, protect from death and disease in a variety of animal models. However, clinical trials of PcrV-binding antibody-based products have thus far failed to demonstrate benefit. Prior candidates were derivations of antibodies identified using protein-immunized animal systems and required extensive engineering to optimize binding and/or reduce immunogenicity. Of note, PA infections are common in people with cystic fibrosis (pwCF), who are generally believed to mount normal adaptive immune responses. Here, we utilized a tetramer reagent to detect and isolate PcrV-specific B cells in pwCF and, via single-cell sorting and paired-chain sequencing, identified the B cell receptor (BCR) variable region sequences that confer PcrV-specificity. We derived multiple high affinity anti-PcrV monoclonal antibodies (mAbs) from PcrV-specific B cells across three donors, including mAbs that exhibit potent anti-PA activity in a murine pneumonia model. This robust strategy for mAb discovery expands what is known about PA-specific B cells in pwCF and yields novel mAbs with potential for future clinical use.
