Cellular barcoding of protozoan pathogens reveals the within-host population dynamics of Toxoplasma gondii host colonization.

Autor:	Wincott CJ; Department of Life Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, UK., Sritharan G; Department of Life Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, UK.; Department of Biological Sciences, Birkbeck, University of London, Mallet Street, Bloomsbury, London WC1E 7HX, UK., Benns HJ; Department of Life Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, UK.; Department of Chemistry, Imperial College London, White City Campus, London W12 0BZ, UK., May D; Department of Microbiology, Immunology and Cancer Biology at the Carter Immunology Center, University of Virginia School of Medicine, Charlottesville, VA 22908, USA., Gilabert-Carbajo C; Department of Life Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, UK., Bunyan M; Host-Toxoplasma Interaction Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1BF, UK., Fairweather AR; Department of Life Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, UK., Alves E; Department of Life Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, UK., Andrew I; UKRI London Institute of Medical Sciences Genomics Laboratory, Shepherd's Bush, London W12 0NN, UK., Game L; UKRI London Institute of Medical Sciences Genomics Laboratory, Shepherd's Bush, London W12 0NN, UK., Frickel EM; Host-Toxoplasma Interaction Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1BF, UK.; Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Edgbaston B15 2TT, UK., Tiengwe C; Department of Life Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, UK., Ewald SE; Department of Microbiology, Immunology and Cancer Biology at the Carter Immunology Center, University of Virginia School of Medicine, Charlottesville, VA 22908, USA., Child MA; Department of Life Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, UK.
Jazyk:	angličtina
Zdroj:	Cell reports methods [Cell Rep Methods] 2022 Aug 22; Vol. 2 (8), pp. 100274. Date of Electronic Publication: 2022 Aug 22 (Print Publication: 2022).
DOI:	10.1016/j.crmeth.2022.100274
Abstrakt:	Cellular barcoding techniques are powerful tools to understand microbial pathogenesis. However, barcoding strategies have not been broadly applied to protozoan parasites, which have unique genomic structures and virulence strategies compared with viral and bacterial pathogens. Here, we present a CRISPR-based method to barcode protozoa, which we successfully apply to Toxoplasma gondii and Trypanosoma brucei . Using libraries of barcoded T. gondii , we evaluate shifts in the population structure from acute to chronic infection of mice. Contrary to expectation, most barcodes were present in the brain one month post-intraperitoneal infection in both inbred CBA/J and outbred Swiss mice. Although parasite cyst number and barcode diversity declined over time, barcodes representing a minor fraction of the inoculum could become a dominant population in the brain by three months post-infection. These data establish a cellular barcoding approach for protozoa and evidence that the blood-brain barrier is not a major bottleneck to colonization by T. gondii . Competing Interests: The authors declare no competing interests. (© 2022 The Author(s).)
Databáze:	MEDLINE
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