Article

Modes of action of Leishmanicidal antimicrobial peptides.

Immunity & Infection Research Centre, Vancouver Coastal Health Research Institute, Vancouver, BC, Canada.
Future Microbiology (Impact Factor: 3.82). 09/2012; 7:1047-59. DOI: 10.2217/fmb.12.85
Source: PubMed

ABSTRACT Leishmaniasis is one of the major neglected tropical diseases of the world. It is present in 88 countries with an estimated number of 500,000 cases of visceral leishmaniasis and 1.5 million cases of cutaneous disease. No effective vaccinations are available against leishmaniasis and the efficacy of existing treatments is compromised due to the emergence of drug resistance. Thus, there is an urgent need to develop new compounds with antileishmanial activity. Antimicrobial peptides have potential as novel antileishmanial therapy, either for use alone or in combination with current drug regimens. The modes of action of these peptides against Leishmania includes: membrane disruption leading to necrotic cell death; induction of apoptosis; binding to intracellular target(s); and indirect effects via immunomodulation of host immune cells. This article reviews the mechanisms of action of antimicrobial peptides with leishmanicidal activity.

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    • "r , final results of both experimental studies have not yet been published . Another important protozoal infection is leishmaniasis , which is one of the main neglected tropical infections of the world with occurrence in 88 countries and an estimated num - ber of 500 , 000 cases of visceral form and 1 . 5 million cases of cutaneous leishmaniasis ( Marr et al . 2012 ) . Drug resistance compromises present treatment options and absence of effec - tive vaccination warrants to search for new compounds with anti - leishmanial activity . Nanotechnology is implied in two different directions : the development of nano - liposomal for - mulations containing conventional anti - leishmanial drugs , for insta"
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    ABSTRACT: Antimicrobial peptides (AMPs) are multifunctional components of the innate immune system. Chemo- therapeutic agents used for treatment of visceral leishmaniasis (VL) are now threatened due to the emer gence of acquired drug resistance and toxicity. AMPs are attractive alternative to conventional pharmaceuticals. In this study, first time we explored the antileishmanial activity of spinigerin originally derived from Pseudacanthotermes spiniger. Leishmania donovani promastigotes present apoptosis-like cell death upon exposure to spinigerin (IC50, 150 lM). The infection rate was reduced by 20% upon exposure to 150 lM spinigerin but no cytotoxicity on host macrophages was observed. Elevation of intracellular ROS level and down-regulation of two ROS detoxifying enzymes, ascorbate peroxidase (APx) and trypa- nothione reductase (TR) suggested essential role of ROS machinery during spinigerin mediated cell death. About 97% cell population was found to be Annexin-V positive; 44% cells being highly Annexin-V positive. Moreover, we observed morphological changes like cell rounding, nuclear condensation, oligonucleoso- mal DNA degradation and TUNEL positive cells without loss of membrane integrity upon spinigerin exposure, suggests apoptosis-like death. Interestingly, collapse in mitochondrial membrane potential and increased level of intracellular ROS and calcium were not associated with caspase like activity. Computational analysis suggests spiningerin interacts with trypanothione reductase and thus probably interferes its function to detoxify the toxic ROS level. Therefore, spinigerin induces apoptosis-like cell death in L. donovani in a caspase-independent manner. The study elucidates the antileishmanial property
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