PKAc is not required for the preerythrocytic stages of<i>Plasmodium berghei</i>

Choudhary, Hadi Hasan; Gupta, Roshni; Mishra, Satish

doi:10.26508/lsa.201900352

Cited by 20 publications

(14 citation statements)

References 60 publications

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“…A similar pathway may operate in Plasmodium sporozoites, where a shift from low to high K+ is associated with decreased CT activity, possibly reflecting the downregulation of microneme secretion (Kumar et al, 2007). Using the Flp/FRT‐based conditional mutagenesis system (Carvalho et al, 2004), Choudhary et al reported that the catalytic subunit of PKA (PKAc) is not required for sporozoite motility and hepatocyte infection (Choudhary et al, 2019). However, incomplete PKA depletion due to protein carryover cannot be ruled out, as was observed for PKG using the same genetic system (Falae et al, 2010; Govindasamy et al, 2016).…”

Section: Signal Transduction In Plasmodium Sporozoites During Migration and Invasionmentioning

confidence: 99%

Plasmodium sporozoites on the move: Switching from cell traversal to productive invasion of hepatocytes

Loubens

Vincensini

Fernandes

et al. 2020

Molecular Microbiology

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Parasites of the genus Plasmodium, the etiological agent of malaria, are transmitted through the bite of anopheline mosquitoes, which deposit sporozoites into the host skin. Sporozoites migrate through the dermis, enter the bloodstream, and rapidly traffic to the liver. They cross the liver sinusoidal barrier and traverse several hepatocytes before switching to productive invasion of a final one for replication inside a parasitophorous vacuole. Cell traversal and productive invasion are functionally independent processes that require proteins secreted from specialized secretory organelles known as micronemes. In this review, we summarize the current understanding of how sporozoites traverse through cells and productively invade hepatocytes, and discuss the role of environmental sensing in switching from a migratory to an invasive state. We propose that timely controlled secretion of distinct microneme subsets could play a key role in successful migration and infection of hepatocytes. A better understanding of these essential biological features of the Plasmodium sporozoite may contribute to the development of new strategies to fight against the very first and asymptomatic stage of malaria.

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Section: Signal Transduction In Plasmodium Sporozoites During Migration and Invasionmentioning

confidence: 99%

Plasmodium sporozoites on the move: Switching from cell traversal to productive invasion of hepatocytes

Loubens

Vincensini

Fernandes

et al. 2020

Molecular Microbiology

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“…Western blotting was performed as described previously (Choudhary, Gupta, & Mishra, 2019). Briefly, salivary gland sporozoites and schizonts were obtained as described above and total cell lysates were prepared in SDS sample buffer.…”

Section: Western Blottingmentioning

confidence: 99%

Secreted protein with altered thrombospondin repeat (SPATR) is essential for asexual blood stages but not required for hepatocyte invasion by the malaria parasite Plasmodium berghei

Gupta

Mishra

Choudhary

et al. 2019

Molecular Microbiology

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Upon entering its mammalian host, the malaria parasite productively invades two distinct cell types, that is, hepatocytes and erythrocytes during which several adhesins/invasins are thought to be involved. Many surface‐located proteins containing thrombospondin Type I repeat (TSR) which help establish host–parasite molecular crosstalk have been shown to be essential for mammalian infection. Previous reports indicated that antibodies produced against Plasmodium falciparum secreted protein with altered thrombospondin repeat (SPATR) block hepatocyte invasion by sporozoites but no genetic evidence of its contribution to invasion has been reported. After failing to generate Spatr knockout in Plasmodium berghei blood stages, a conditional mutagenesis system was employed. Here, we show that SPATR plays an essential role during parasite's blood stages. Mutant salivary gland sporozoites exhibit normal motility, hepatocyte invasion, liver stage development and rupture of the parasitophorous vacuole membrane resulting in merosome formation. But these mutant hepatic merozoites failed to establish a blood stage infection in vivo. We provide direct evidence that SPATR is not required for hepatocyte invasion but plays an essential role during the blood stages of P. berghei.

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“…The amplified product was cloned into the pCR 2.1-TOPO vector. For the normalization of transcripts, Hsp70 was used (Choudhary et al , 2019). Total RNA was isolated from blood stage schizonts (Schz), liver stages (LS), midgut (MG), and salivary gland (SG) sporozoites using TRIzol reagent (Takara Bio, Japan) and an RNA isolation kit (Genetix, India) following the manufacturers’ instructions.…”

Section: Methodsmentioning

confidence: 99%

A novel glideosome-associated protein S14 coordinates sporozoite gliding motility and infectivity in mosquito and mammalian hosts

Ghosh,

Varshney,

Narwal

et al. 2023

Preprint

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Plasmodium sporozoites are the infective forms of the malaria parasite in the vertebrate host. Gliding motility allows sporozoites to migrate and invade the salivary gland and hepatocytes. Invasion is powered by an actin-myosin motor complex linked to glideosome. However, the gliding complex and the role of several glideosome-associated proteins (GAPs) are poorly understood. In silico analysis of a novel protein, S14, which is uniquely upregulated in salivary gland sporozoites, suggested its association with glideosome-associated proteins. We confirmed S14 expression in sporozoites using real-time PCR. Further, the S14 gene was endogenously tagged with 3XHA-mCherry to study expression and localization. We found its expression and localization on the inner membrane of sporozoites. By targeted gene deletion, we demonstrate that S14 is essential for sporozoite gliding motility, salivary gland, and hepatocyte invasion. The gliding and invasion-deficient S14 KO sporozoites showed normal expression and organization of IMC and surface proteins. Using in silico and the yeast two-hybrid system, we showed the interaction of S14 with the glideosome-associated proteins GAP45 and MTIP. Together, our data show that S14 is a glideosome-associated protein and plays an essential role in sporozoite gliding motility, which is critical for the invasion of the salivary gland, hepatocyte, and malaria transmission.

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PKAc is not required for the preerythrocytic stages ofPlasmodium berghei

Cited by 20 publications

References 60 publications

Plasmodium sporozoites on the move: Switching from cell traversal to productive invasion of hepatocytes

Plasmodium sporozoites on the move: Switching from cell traversal to productive invasion of hepatocytes

Secreted protein with altered thrombospondin repeat (SPATR) is essential for asexual blood stages but not required for hepatocyte invasion by the malaria parasite Plasmodium berghei

A novel glideosome-associated protein S14 coordinates sporozoite gliding motility and infectivity in mosquito and mammalian hosts

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