L.major

Leishmaniasis

Leishmaniasis is a vector borne parasitic disease, caused by protozoan species Leishmania and spread by the bite of infected phlebotomine sand flies. Two million new cases are reported every year and 1/10th of the world's population is at the risk of infection. Leishmaniasis is found in parts of about 88 countries, majorly spread in the tropical and subtropical regions of the world. The genome sequence provides insights into the unique aspects of the biology of these parasites. The 32.8 Mb haploid genome of L.major is sequenced into 36 chromosome and 911 RNA genes, 39 pseudogenes and 8272 protein coding genes are predicted, of which 36% can be ascribed a putative function. Recent developments in genome sequencing for L.major and lipidomic tools conceive a powerful platform for the study of lipid metabolism in Leishmania. Lipid concentration changes in biological systems reflects regulation at multiple spatial and dynamic scales,e.g:biochemical reactions in the cells.

The Leishmania parasite has a digenetic life cycle that alternates between an intracellular non-flagellated amastigote form found in mammalian macrophages which can be found throughout the body, and a number of flagellated promastigote forms, which are confined to the gut of the Phlebotomine sandfly.

Life cycle of Leishmaniasis

• When the sand fly vector feeds on the human blood, the protozoan parasites get transmitted in the host body. The polymorphonuclear neutrophil granulocytes (PMN) move out from the bloodstream, through the vessels endothelial layer, to the site of the infected tissue.
• They carry out the first immune response and phagocytize the parasites, leading to an inflammation. These activated PMNs secrete chemokines, IL-8 particularly, to attract further granulocytes and stimulate them to phagocytosis.
• The lifespan of neutrophil granulocytes is quite short. They circulate in bloodstream for about 6 or 10 hours after leaving bone marrow, whereupon they undergo spontaneous apoptosis.
• The pathogens induce the PMN to produce the chemokines MIP-1a and MIP-1 (macrophage inflammatory protein) to recruit macrophages, which then engulf these pathogens (a) In the mammalian host: The female sand fly by feeding on host blood, transfers the promastigotes, which invade the wound and are engulfed by mononuclear macrophagocytes, in which they multiply by binary fission, until the host cell is destroyed, whereupon new macrophage cells are parasitized. (b) In the digestive tract of sand fly: Female sand fly by sucking blood of an infected human, gets injected by the protozoans.
• In its intestine, macrophagocyte is digested and amastigotes transform into promastigotes and then multiply by binary fission.

Forms of Leishmaniasis

There are several different forms of leishmaniasis. Depending upon the species and the reaction of the individual, several different syndromes are seen. The most common are the cutaneous and visceral forms.

Severity of lesions caused by cutaneous Leishmaniasis

Cutaneous Leishmaniasis:

It causes severe lesions and ulcers, and eventually results into disfigurement and disability, leading to social and psychological stigma as grave consequences of the disease. The significant causative agent of cutaneous leishmaniasis is L.major.

The L.major genome having been decoded recently, the availability of the entire genetic content would provide the foundation for the identification and comprehensive functional analysis of virulence factors, critical enzymes in key metabolic pathways, and potential vaccine candidates. All provide crucial information for the development of new therapies for the cutaneous leishmaniasis.

Geographic Distribution of Leishmaniasis

Leishmania is endemic throughout North Africa, parts of Europe, the Middle-East and Central and South America and occurs in epidemics with high mortality in East Africa, parts of the Indian subcontinent and South America.

Genome of Leishmania

The genome sequences provide insights into the unique aspects of the biology of these parasites. The 32.8-megabase haploid genome of Leishmania major (Friedlin strain) is sequenced into 36 chromosomes and 911 RNA genes, 39 pseudogenes, and 8272 protein-coding genes are predicted, of which 36% can be ascribed a putative function. Excluding the transport reactions, the percentage of intracellular reactions participating in lipid metabolism in L.major was the greatest, when compared to reactions across other metabolic subsystems.

In order to address the intricacies of lipid regulation, it is quite obligatory to analyze the lipid metabolic mechanism