Abstract
C-mannosylation was recently identified in the thrombospondin-related anonymous protein (TRAP) from Plasmodium falciparum salivary gland sporozoites. A candidate P. falciparum C-mannosyltransferase (PfDPY-19) was demonstrated to modify thrombospondin type 1 repeat (TSR) domains in vitro, exhibiting a different acceptor specificity than their mammalian counterparts. According to the described minimal acceptor of PfDPY19, several TSR domain-containing proteins of P. falciparum could be C-mannosylated in vivo. However, the relevance of this protein modification for the parasite viability remains unknown. In the present study, we used CRISPR/Cas9 technology to generate a PfDPY19 null mutant, demonstrating that this glycosyltransferase is not essential for the asexual blood development of the parasite. PfDPY19 gene disruption was not associated with a growth phenotype, not even under endoplasmic reticulum-stressing conditions that could impair protein folding. The data presented in this work strongly suggest that PfDPY19 is unlikely to play a critical role in the asexual blood stages of the parasite, at least under in vitro conditions.
Highlights
Malaria remains one of the most serious global infectious diseases
Taking into consideration the proposed roles for some of the putative acceptors of Pf DPY19 in the asexual blood stages, we aimed to describe the relevance of the gene for the viability of P. falciparum by disrupting it and analysing the growth phenotype of ΔPf DPY19 mutant parasites
The recent functional characterization of P. falciparum PoFUT2 suggests a critical role of O-fucosylation during the infection of the mosquito host (Lopaticki et al, 2017), these results could not be replicated in an independent study (Sanz et al, 2019)
Summary
Malaria remains one of the most serious global infectious diseases. Only in 2017, it was responsible for 219 million cases and 435 000 deaths worldwide (World Health Organization, 2018). It is generally accepted that malaria elimination from the remaining endemic countries will not be possible with currently available strategies (Alonso et al, 2011). In this regard, a better understanding of the numerous gaps of knowledge in the complex biology of the parasite would facilitate the rationale design of new interventions. The functional characterization of P. falciparum TSR domain-containing proteins revealed the essential roles that these effectors play in processes involved in cell invasion, egression and transmission of the parasite through the mosquito stages. A secreted protein with altered thrombospondin repeat domain (SPATR) is expressed at multiple stages of the parasite such as sporozoites, asexual blood stages and gametocytes. Antibodies raised against SPATR block hepatocyte invasion by sporozoites; the biological relevance of SPATR during other stages of the parasite has not been addressed (Chattopadhyay et al, 2003)
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