NEW BIOMOLECULES TO FIGHT DRUG RESISTANCE IN KALA-AZAR
New biomolecules to fight drug resistance in Kala-azar
Scientists at the Department of Biotechnology’s National Centre for Cell Science (DBT-NCCS) in Pune have been exploring ways to tackle miltefosine (a drug used to treat Leishmaniasis/Kala-azar) resistance.
- Protein molecules, called transporter proteins, play a major role in carrying miltefosine into and out of the parasite’s body, which comprises a single cell.
- ‘P4ATPase-CDC50’: It is a protein and responsible for the intake of the drug by the parasite. Another protein, called ‘P-glycoprotein’, is responsible for throwing this drug out from within the parasite’s body.
- A decrease in the activity of the P4ATPase-CDC50 protein and an increase in the activity of the P-glycoprotein results in fewer amounts of miltefosine being accumulated inside the parasite’s body, thus causing it to become resistant to the drug.
- Scientists worked with one of the species of Leishmania that causes infection, called Leishmania major.
- Scientists have also tried to manipulate these transporter proteins in the species in a manner that would result in increased uptake of the drug and decrease in its being thrown out of the parasite’s body.
- Kala-azar is a neglected tropical disease affecting almost 100 countries including India.
- The disease is caused by a parasite called Leishmania, which is transmitted through the bite of sandflies.
- There are three main forms of leishmaniasis – visceral, which affects multiple organs and is the most serious form of the disease, cutaneous, which causes skin sores and is the most common form; and mucocutaneous, which causes skin and mucosal lesion.
- Visceral leishmaniasis, which is commonly known as Kala-azar in India. The only drug available against leishmaniasis, miltefosine, is rapidly losing its effectiveness because of emerging resistance to this drug due to a decrease in its accumulation inside the parasite, which is necessary for the drug to kill the parasite.