Leishmania , a protozoan pathogen, causes various types of Leishmaniasis, visceral Leishmaniasis (VL) being fatal in over 95% of the cases if left untreated. Transmission occurs by the bite of infected female phlebotomine sandflies. As per WHO, it is one of the top parasitic diseases with mortality potential. Hemoglobin receptor (HbR) has been shown to mediate Hemoglobin (Hb) endocytosis in Leishmania . The acquisition of heme is crucial for the parasite to survive in the host. Drugs currently in use for the disease are toxic, and resistance is common. Therefore, it is essential to identify a chemotherapeutic target that may be used to treat Leishmaniasis. Our group has already established that immunisation of HbR in different animal models has proved to decrease parasitic burden to upto 99%. In this study, we isolated the 52kDa HbR followed by characterisation by circular dichroism which indicated predominantly alpha helices. Various biophysical techniques such as steady-state intrinsic fluorescence spectroscopy, surface plasmon resonance, Isothermal titration calorimetry, and fluorescence anisotropy were implied to investigate the interaction between HbR and Hb. HbR binds the Hb with high affinity. Suitable mutants were made to identify the specific amino acids involved in the interaction which were then characterized by the aforementioned biophysical methods. These results could contribute to find suitable inhibitors interaction. Preventing the binding of HbR with Hb can prevent the parasite to grow and infect the host and hence can prove to be an effective therapeutic intervention for leishmaniasis.
Gaur et al. (Sun,) studied this question.