Biology subjects

Szoor, B.

Publications and source records attributed to Szoor, B..

3 recordsLinked to original sources

bioRxiv2023

A conserved trypanosomatid differentiation regulator controls substrate attachment and morphological development in Trypanosoma congolense

Trypanosomatid parasites undergo developmental regulation to adapt to the different environments encountered during their life cycle. In Trypanosoma brucei, a genome wide selectional screen previously identified a regulator of the protein family ESAG9, which is highly expressed in stumpy forms, a morphologically distinct bloodstream stage adapted for tsetse transmission. This regulator, TbREG9.1, has an orthologue in Trypanosoma congolense, despite the absence of a stumpy morphotype in that parasite species, which is an important cause of livestock trypanosomosis. RNAi mediated gene silencing of TcREG9.1 in Trypanosoma congolense caused a loss of attachment of the parasites to a surface substrate in vitro, a key feature of the biology of these parasites that is distinct from T. brucei. This detachment was phenocopied by treatment of the parasites with a phosphodiesterase inhibitor, which also promotes detachment in the insect trypanosomatid Crithidia fasciculata. RNAseq analysis revealed that TcREG9.1 silencing caused the upregulation of mRNAs for several classes of surface molecules, including transferrin receptor-like molecules, immunodominant proteins, and molecules related to those associated with stumpy development in T. brucei. Depletion of TcREG9.1 in vivo also generated an enhanced level of parasites in the blood circulation consistent with reduced parasite attachment to the microvasculature. The morphological progression to insect forms of the parasite was also perturbed. We propose a model whereby TcREG9.1 acts as a regulator of attachment and development, with detached parasites being adapted for transmission. Author summaryTrypanosoma congolense is a major cause of livestock trypanosomosis in sub-Saharan Africa where it contributes to lost economic productivity and poverty. These parasites differ in two key respects from the better-studied African trypanosomes, Trypanosoma brucei. Firstly, T. congolense adheres to surfaces in vitro and in the vaculature in vivo. Secondly, they lack a morphologically distinct transmission stage equivalent to the stumpy form of T. brucei. In the current work we identify a T congolense orthologue of a key developmental regulator in T. brucei, REG9.1, previously identified by a genome-wide RNAi screen. By RNA interference in transgenic T. congolense we demonstrate that TcREG9.1 functions both in parasite adherence in vitro and in vivo, and also in parasite development. The work provides a first insight into the unusual adherence and developmental biology of T. congolense and also suggests a possible model for how these characteristics interact to promote disease spread.

microbiology↗

bioRxiv2023

When is a slender not a slender? The cell-cycle arrest and scarcity of slender parasites challenges the role of bloodstream trypanosomes in infection maintenance

The development of Trypanosoma brucei in its mammalian host is marked by a distinct morphological change as replicative "slender" forms differentiate into cell-cycle arrested "stumpy" forms in a quorum-sensing dependent manner. Although stumpy forms dominate chronic infections at the population level, the proportion of replicative parasites at the individual cell level and the irreversibility of arrest in the bloodstream is unclear. Here, we experimentally demonstrate that developmental cell cycle arrest is definitively irreversible in acute and chronic infections in mice. Furthermore, analysis of replicative capacity and single-cell transcriptome profiling reveals a temporal hierarchy, whereby cell-cycle arrest and appearance of a stumpy-like transcriptome precedes irreversible commitment and morphological change. Unexpectedly, we show that proliferating parasites are exceptionally scarce in the blood after infections are established. This challenges the ability of bloodstream trypanosomes to sustain infection by proliferation or antigenic variation, these parasites instead being overwhelmingly adapted for transmission.

microbiology↗

bioRxiv2019

Positional dynamics and glycosomal recruitment of developmental regulators during trypanosome differentiation

Glycosomes are peroxisome-related organelles that compartmentalise the glycolytic enzymes in kinetoplastid parasites. These organelles are developmentally regulated in their number and composition, allowing metabolic adaptation to the parasites needs in the blood of mammalian hosts or within their arthropod vector. A protein phosphatase cascade regulates differentiation between parasite developmental forms, comprising a tyrosine phosphatase, TbPTP1, that dephosphorylates and inhibits a serine threonine phosphatase TbPIP39 that promotes differentiation. When TbPTP1 is inactivated, TbPIP39 is activated and during differentiation becomes located in glycosomes. Here we have tracked TbPIP39 recruitment to glycosomes during differentiation from bloodstream stumpy forms to procyclic forms. Detailed microscopy and live cell imaging during the synchronous transition between life cycle stages revealed that in stumpy forms, TbPIP39 is located at a periflagellar pocket site closely associated with TbVAP, that defines the flagellar pocket endoplasmic reticulum. TbPTP1 is also located at the same site in stumpy forms, as is REG9.1, a regulator of stumpy-enriched mRNAs. This site provides a molecular node for the interaction between TbPTP1 and TbPIP39. Within 30 minutes of the initiation of differentiation TbPIP39 relocates to glycosomes whereas TbPTP1 disperses to the cytosol. Overall, the study identifies a stumpy regulatory nexus (STuRN) that co-ordinates the molecular components of life cycle signalling and glycosomal development during transmission of Trypanosoma brucei.\n\nImportanceAfrican trypanosomes are parasites of sub-Saharan Africa responsible for both human and animal disease. The parasites are transmitted by tsetse flies and completion of their life cycle involves progression through several development steps. The initiation of differentiation between blood and tsetse forms is signalled by a phosphatase cascade, ultimately trafficked into peroxisome-related organelles called glycosomes that are unique to this group of organisms. Glycosomes undergo substantial remodelling of their composition and function during the differentiation step but how this is regulated is not understood. Here we identify a cytological site where the signalling molecules controlling differentiation converge before the dispersal of one of them into glycosomes. This coincides with a specialised ER site that may contribute to glycosome developmental biogenesis or regeneration. In combination, the study provides the first insight into the spatial co-ordination of signalling pathway components in trypanosomes as they undergo cell-type differentiation.

microbiology↗