Deep Insight into the Phosphatomes of Parasitic Protozoa and a Web Resource ProtozPhosDB

Abstract

Phosphorylation dynamically regulates the function of proteins by maintaining a balance between protein kinase and phosphatase activity. A comprehensive understanding of the role phosphatases in cellular signaling is lacking in case of protozoans of medical and veterinary importance worldwide. The drugs used to treat protozoal diseases have many undesired effects and the development of resistance, highlights the need for new effective and safer antiprotozoal agents. In the present study we have analyzed phosphatomes of 15 protozoans of medical significance. We identified ~2000 phosphatases, out of which 21% are uncharacterized proteins. A significant positive correlation between phosphatome and proteome size was observed except for E. histolytica, having highest density of phosphatases irrespective of its proteome size. A difference in the number of phosphatases among different genera shows the variation in the signaling pathways they are involved in. The phosphatome of parasites is dominated by ser/thr phosphatases contrary to the vertebrate host dominated by tyrosine phosphatases. Phosphatases were widely distributed throughout the cell suggesting physiological adaptation of the parasite to regulate its host. 20% to 45% phosphatome of different protozoa consists of ectophosphatases, i.e. crucial for the survival of parasites. A database and a webserver “ProtozPhosDB” can be used to explore the phosphatomes of protozoans of medical significance.

Cooperative Interactions between Trichomonas vaginalis and Associated Bacteria Enhance Paracellular Permeability of the Cervicovaginal Epithelium by Dysregulating Tight Junctions

“…On the other hand, phosphatase activity has been found in various cellular compartments of T. vaginalis, including on its surface and in secreted fractions (50); those findings have been recently supported by proteomics data (51,52). In fact, the T. vaginalis genome has experienced a dramatic expansion of phosphatase gene families displaying the largest repertoire among protozoans (53,54). Therefore, phosphatases should play key roles in various pathophysiological aspects of this parasite and might be implicated in the modulation of the hEC PcP.…”

Protein Phosphatase PP2C Identification in Entamoeba spp

“…A comparative in silico analysis of phosphatases has been carried out in a variety of protozoan parasites, showing that serine/threonine phosphatases constitute the highest proportion of all protein phosphatases as well as among those on the plasma membrane [ 58 ]. Serine phosphatases are known to take part in L-serine biosynthetic pathways in E. histolytica and E. invadens [ 59 ].…”

Cdc42/Rac Interactive Binding Containing Effector Proteins in Unicellular Protozoans With Reference to Human Host: Locks of the Rho Signaling

“…It has been demonstrated the role of cytoskeleton assembly in the Entamoeba and a human macrophage ( Marchat et al, 2020 ). Phagocytosis is a dynamic and regulated process that involved a varsity of proteins ranging from actin-binding protein, motor protein, small GTPases, kinases and phosphatases ( Godbold and Mann, 1998 ; Marquay Markiewicz et al, 2011 ; Anwar and Gourinath, 2016 ; Gautam et al, 2017 ; Agarwal et al, 2019 ; Gautam et al, 2019 ). ∼20 Rho family GTPases and numerous downstream signaling effectors are present in these single-celled trophozoites that coordinate actin dynamics in pathogenesis-related processes.…”