Fatty Acid Profiles of Leishmania major Derived from Human and Rodent Hosts in Endemic Cutaneous Leishmaniasis Areas of Tunisia and Algeria

Abstract

Leishmaniasis is a protozoal vector-borne disease that affects both humans and animals. In the Mediterranean Basin, the primary reservoir hosts of Leishmania spp. are mainly rodents and canids. Lipidomic approaches have allowed scientists to establish Leishmania spp. lipid profiles for the identification of cell stage specific biomarkers, drug mechanisms of action, and host immune response. Using an in silico approach of global network interaction between genes involved in fatty acid (FA) synthesis followed by the GC-MS approach, we were able to characterize the fatty acid profiles of L. major derived from human and rodent hosts. Our results revealed that the lipid profile of L. major showed similarities and differences with those already reported for other Leishmania species. Phospholipids are the predominant lipid class. FA composition of rodent parasites was characterized by a lower abundance of the precursor C18:2(n-6). One of the rodent clones, which also expressed the lowest lipid abundance in PL and TAG, was the least sensitive clone to the miltefosine drug and has the lowest infection efficiency. Our findings suggest that the lipid composition variation may explain the response of the parasite toward treatment and their ability to infect their host.

Synchrotron-Infrared Microspectroscopy of Live Leishmania major Infected Macrophages and Isolated Promastigotes and Amastigotes

“…In addition, Bouabid et al demonstrated the predominance of polyunsaturated fatty acids in L. major promastigote by mass spectrometry . The current study shows that the infrared spectroscopic approach corroborates the findings of the gold standard lipidomic approaches.…”

Label-Free Mass Spectrometry Proteomics Reveals Different Pathways Modulated in THP-1 Cells Infected with Therapeutic Failure and Drug Resistance Leishmania infantum Clinical Isolates

“…In addition to the two overlapping proteins/transcripts, TFRC and NDK3, some proteins from the two different datasets appear to belong to mutual pathways and interact with each other. Remarkable examples are the subnetworks consisting of PDHX, PDK4, CYC1, BHD1, ACSL1, and ACSL3, involved in biosynthetic processes of fatty acid derivatives, purine ribonucleotides, and the tricarboxylic acid cycle, , that are shared among the DEP and DET datasets. Subsequently, ABCG2 and HMOX, networking with TFRC, ALCAM and PECAM, and AQP9 and PLEK, participate in immune response and the immune system and in vesicle-mediated trafficking .…”

Non-Vesicular Lipid Transport Machinery in Leishmania donovani: Functional Implications in Host-Parasite Interaction

“…Phospholipids (PL) have been reported as the predominant class of lipid in Leishmania sp. The fatty acid (FA) composition was characterized by a lower abundance of the precursor C18:2(n-6) [ 36 , 120 ]. Leishmania sp.…”

“…Promastigote, the extracellular form of the parasite relies on de-novo synthesis of lipids (specifically, glycerophospholipid, sterols and sphingolipids), while intracellular amastigotes form largely depends on host-derived lipids for intracellular growth and survival [ 35 ]. Lipid droplets (LDs), which are observed both inside the parasitophorous vacuole and within parasite cytoplasm may indicates that L. donovani could use LDs as high energy sources for their growth [ 36 ]. The functional implications of exosomes from L. donovani during host-parasite interaction was also reported [ 123 , 124 , 125 , 126 , 127 ].…”

“…Lipids, an essential constituents of eukaryotic cell regulate a diverse array of cellular processes and have been implicated in cellular growth, differentiation, survival, adaptation under stress [ 31 , 32 ]. The essentiality of lipids and their effector molecules in parasite’s cell signaling, cell proliferation, host-parasite interaction and drug susceptibility have been reported in Plasmodium falciparum [ 33 , 34 ], L. donovani [ 35 , 36 , 37 , 38 ], Trypanosoma cruzi [ 39 ], Entamoeba histolytica [ 40 , 41 ] and Giardia lamblia [ 42 , 43 ]. However, molecular mechanisms of intracellular lipid trafficking and their implications in lipid homeostasis and in parasite’s biology have been greatly unexplored.…”