Genome-wide dissection of the quorum sensing signalling pathway in Trypanosoma brucei

Nature
Binny M MonyKeith R Matthews

Abstract

The protozoan parasites Trypanosoma brucei spp. cause important human and livestock diseases in sub-Saharan Africa. In mammalian blood, two developmental forms of the parasite exist: proliferative 'slender' forms and arrested 'stumpy' forms that are responsible for transmission to tsetse flies. The slender to stumpy differentiation is a density-dependent response that resembles quorum sensing in microbial systems and is crucial for the parasite life cycle, ensuring both infection chronicity and disease transmission. This response is triggered by an elusive 'stumpy induction factor' (SIF) whose intracellular signalling pathway is also uncharacterized. Laboratory-adapted (monomorphic) trypanosome strains respond inefficiently to SIF but can generate forms with stumpy characteristics when exposed to cell-permeable cAMP and AMP analogues. Exploiting this, we have used a genome-wide RNA interference library screen to identify the signalling components driving stumpy formation. In separate screens, monomorphic parasites were exposed to 8-(4-chlorophenylthio)-cAMP (pCPT-cAMP) or 8-pCPT-2'-O-methyl-5'-AMP to select cells that were unresponsive to these signals and hence remained proliferative. Genome-wide Ion Torrent based RNAi target ...Continue Reading

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Citations

Feb 11, 2014·Research in Microbiology·Veronica Jimenez
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May 1, 2019·Parasites & Vectors·Mathieu CaylaKeith R Matthews

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Methods Mentioned

BETA
PCRs
PCR
flow cytometry

Software Mentioned

FlowJO
Bedtools
bowtie2
RNAit
Minitab
FastQC
samtools
Cutadapt
GenomicFeatures Bioconductor
R

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African trypanosomiasis, also known as sleeping sickness, is an insect-borne parasitic disease of humans and other animals. It is caused by protozoa of the species Trypanosoma brucei and almost invariably progresses to death unless treated. Discover the latest research on African trypanosomiasis here.