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There are important challenges when investigating individual post-translational modifications (PTMs) or protein interaction network and delineating if PTMs or their changes and cross-talks are involved during infection, disease initiation or as a result of disease progression. Proteomics and in silico approaches now offer the possibility to complement each other to further understand the regulatory involvement of these modifications in parasites and infection biology. Accordingly, the current review highlights key expressed or altered proteins and PTMs are invisible switches that turn on and off the function of most of the proteins. PTMs include phosphorylation, glycosylation, ubiquitylation, palmitoylation, myristoylation, prenylation, acetylation, methylation, and epigenetic PTMs in P. falciparum which have been recently identified. But also other low-abundant or overlooked PTMs that might be important for the parasite's survival, infectivity, antigenicity, immunomodulation and pathogenesis. We here emphasize the PTMs as regulatory pathways playing major roles in the biology, pathogenicity, metabolic pathways, survival, host-parasite interactions and the life cycle of P. falciparum. Further validations and functional characterizations of such proteins might confirm the discovery of therapeutic targets and might most likely provide valuable data for the treatment of P. falciparum, the main cause of severe malaria in human.

The mechanistic (or mammalian) target of rapamycin (mTOR) is considered as a critical regulatory enzyme involved in essential signaling pathways affecting cell growth, cell proliferation, protein translation, regulation of cellular metabolism, and cytoskeletal structure. Also, mTOR signaling has crucial roles in cell homeostasis via processes such as autophagy. Autophagy prevents many pathogen infections and is involved on immunosurveillance and pathogenesis. Immune responses and autophagy are therefore key host responses and both are linked by complex mTOR regulatory mechanisms. In recent years, the mTOR pathway has been highlighted in different diseases such as diabetes, cancer, and infectious and parasitic diseases including leishmaniasis, toxoplasmosis, and malaria. The current review underlines the implications of mTOR signals and intricate networks on pathogen infections and the modulation of this master regulator by parasites. Parasitic infections are able to induce dynamic metabolic reprogramming leading to mTOR alterations in spite of many other ways impacting this regulatory network. Accordingly, the identification of parasite effects and interactions over such a complex modulation might reveal novel information regarding the biology of the abovementioned parasites and might allow the development of therapeutic strategies against parasitic diseases. In this sense, the effects of inhibiting the mTOR pathways are also considered in this context in the light of their potential for the prevention and treatment of parasitic diseases.

The association of leishmaniasis and malignancies in human and animal models has been highlighted in recent years. The misdiagnosis of coexistence of leishmaniasis and cancer and the use of common drugs in the treatment of such diseases prompt us to further survey the molecular biology of Leishmania parasites and cancer cells. The information regarding common expressed proteins, as possible therapeutic targets, in Leishmania parasites and cancer cells is scarce. Therefore, the current study reviews proteins, and investigates the regulation and functions of several key proteins in Leishmania parasites and cancer cells. The up- and down-regulations of such proteins were mostly related to survival, development, pathogenicity, metabolic pathways and vital signalling in Leishmania parasites and cancer cells. The presence of common expressed proteins in Leishmania parasites and cancer cells reveals valuable information regarding the possible shared mechanisms of pathogenicity and opportunities for therapeutic targeting in leishmaniasis and cancers in the future.