Major Molecular Factors Related to Leishmania Pathogenicity

Abstract

Leishmaniasis is a major health problem with 600k - 1M new cases worldwide and 1 billion at risk. It involves a wide range of clinical forms ranging from self-healing cutaneous lesions to systemic diseases that are fatal if not treated, depending on the species of Leishmania. Leishmania sp. are digenetic parasites that have two different morphological stages. Leishmania parasites possess a number of invasive/evasive and pathoantigenic determinants that seem to have critical roles in Leishmania infection of macrophages which leads to successful intracellular parasitism in the parasitophorous vacuoles. These determinants are traditionally known as “virulence factors”, and are considered to be good targets for developing specific inhibitors to attenuate virulence of Leishmania by gene deletions or modifications, thus causing infective, but non-pathogenic mutants for vaccination. Pathway of biosynthesis is critical for keeping the parasite viable and is important for drug designing against these parasites. These drugs are aimed to target enzymes that control these pathways. Accordingly, maintaining low level of parasitic infection and in some cases as a weapon to eradicate infection completely. The current paper focuses on several virulence factors as determinants of Leishmania pathogenicity, as well as the metabolites produced by Leishmania to secure its survival in the host.

Phenotypical Differences between Leishmania (Leishmania) amazonensis PH8 and LV79 Strains May Impact Survival in Mammal Host and in Phlebotomine Sand Flies

“…Permissive vectors such as L. longipalpis and L. migonei can sustain the infection of several Leishmania species, including L. ( L. ) amazonensis [ 12 , 19 ]. We thus infected L. longipalpis with PH8 and LV79 promastigotes and analyzed Leishmania abundance at different time points.…”

“…Once in the vertebrate host, promastigotes are taken by phagocytes and differentiate into amastigotes inside macrophages [ 3 , 11 ]. To survive inside the hosts, the parasite relies on several molecules involved in “invasion and evasion”, termed virulence factors [ 3 , 12 ]. The most studied factors in Leishmania are glycoprotein 63 (GP63) and lipophosphoglycan (LPG), abundant molecules of the promastigote coat that contribute to resistance to complement lysis, parasite phagocytosis, and intracellular survival, among others [ 13 , 14 , 15 , 16 , 17 , 18 , 19 ].…”

Leishmania species: A narrative review on surface proteins with structural aspects involved in host–pathogen interaction

“…These two components are connected by a phosphodiester bond (Forestier et al, 2015). It is made up of repeating, linear phosphodiester linkages connecting 15–30 units of phosphorylated oligosaccharides (Al‐Khalaifah, 2022). Promastigotes and amastigotes have significantly different side chain compositions and LPG core positioning on their glycocalyx surface (Cummings et al, 2022).…”

Immunoproteomics and phage display in the context of leishmaniasis complexity

“…CL is usually limited to an ulcer that is self-curing; however, it can evolve into severe manifestations, such as ML and CDL, which cause morbidity in patients. VL can be fatal if acute and untreated, while Post-kala-azar leishmaniasis is a skin manifestation that can occur in the populations of some countries after VL treatment ( 5 – 7 ).…”