The interaction and survival of pathogens in hostile environments and in confrontation with host immune responses are important mechanisms for the establishment of infection. Ectophosphatases are enzymes localized at the plasma membrane of cells, and their active sites face the external medium rather than the cytoplasm. Once activated, these enzymes are able to hydrolyze phosphorylated substrates in the extracellular milieu. Several studies demonstrated the presence of surface-located ecto-phosphatases in a vast number of pathogenic organisms, including bacteria, protozoa, and fungi. Little is known about the role of ecto-phosphatases in host-pathogen interactions. The present paper provides an overview of recent findings related to the virulence induced by these surface molecules in protozoa and fungi. 1. Introduction Cells are exposed to diverse environmental stimuli throughout their cycles in all biological systems. Protein phosphorylation and dephosphorylation are central events in cell recognition of external and internal signals, leading to specific responses. While protein kinases transfer a phosphate group from ATP to a protein (i.e., phosphorylate), protein phosphatases catalyze the removal of phosphate groups from specific residues of proteins (i.e., dephosphorylate) [1, 2]. The balance between the antagonistic activities of protein kinases and phosphatases are responsible for many cellular functions, including metabolic pathways, cell-cell communication, proliferation, and gene transcription [3]. The complete genome sequencing of various microorganisms made it possible to assemble the kinome and phosphatome of a few trypanosomatids [4, 5]. These strategies have brought new perspectives of researches in the areas of biochemistry, physiology, and genetics, providing knowledge about the microorganisms’ life cycles, as well as predicting diagnostic biomarkers, novel drug targets and vaccine candidates against parasitic infections. Parasites engage a plethora of surface and secreted molecules in order to attach and enter mammalian cells. Some of these molecules are involved in triggering specific signaling pathways both in the parasite and the host cell, which are critical for parasite entry and survival [6]. Plasma membranes of cells contain enzymes that are oriented with their active sites facing the external medium rather than the cytoplasm, which are important for host-parasite interactions [7, 8]. In the case of an ectoenzyme other criteria can be included as: (1) the enzyme has to act on extracellular substrate, (2) cellular integrity is
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