Lipase precursor like protein promotes miltefosine tolerance in Leishmania donovani by enhancing parasite infectivity and eliciting anti-inflammatory responses in host macrophages.

Lipase precursor like protein promotes miltefosine tolerance in Leishmania donovani by enhancing parasite infectivity and eliciting anti-inflammatory responses in host macrophages. Antimicrob Agents Chemother. 2018 Oct 08;: Authors: Deep DK, Singh R, Kulshrestha A, Wajid S, Salotra P Abstract Oral drug miltefosine (MIL) was introduced in the Indian subcontinent in the year 2002 for the treatment of visceral leishmaniasis (VL). However, recent reports on its declining efficacy and increasing relapse rates pose a serious concern. An understanding of the factors contributing to MIL tolerance in Leishmania parasites is critical. In the present study, we assessed the role of lipase precursor like protein (Lip) in conferring tolerance towards miltefosine by episomally overexpressing Lip into L. donovani (LdLip++). We observed significant increase (∼3 fold) in MIL IC50 both at promastigote (3.90 ± 0.68 µM, P<0.05) and at intracellular amastigote (9.10 ± 0.60 µM, P<0.05) stages compared to the wild type counterpart (LdNeo; MIL IC50 promastigote 1.49 ± 0.20 µM; MIL IC50 amastigote 3.95 ± 0.45 µM). LdLip++ parasites exhibited significantly (P<0.05) increased infectivity to host macrophages, increased metacyclogenesis and tolerance to MIL induced oxidative stress. The susceptibility of LdLip++ towards other antileishmanial drugs (sodium antimony gluconate and amphotericin B) remained unchanged. In comparison to LdNeo, the LdL...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research