Dicentracin-Like from Asian sea bass Fish and Moronecidine-Like from Hippocampus Comes : Two Candidate Antimicrobial Pep
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Dicentracin‑Like from Asian sea bass Fish and Moronecidine‑Like from Hippocampus Comes: Two Candidate Antimicrobial Peptides Against Leishmanina major Infection Mohsen Mohammadi1 · Amin Moradi Hasan‑Abad2 · Parva Dehghani1 · Iraj Nabipour1 · Mona Roozbehani3 · Andrew Hemphill4 · Marzieh Taherzadeh5 · Mohammad Ali Mohaghegh6,7 · Moradali Fouladvand1,5 Accepted: 22 October 2020 © Springer Nature B.V. 2020
Abstract Anti-Leishmanial drug therapy faces significant challenges related to cytotoxicity and drug resistance. Thus, new and efficient anti-Leishmanial drugs need to be identified. Due to their broad-spectrum antimicrobial and also immunomodulatory activities, antimicrobial peptides (AMPs) have attracted considerable attention. In this study, we comparatively assessed the anti-Leishmanial activities of two recently identified AMPs (dicentracin-like and moronecidine-like) and the well-known AMP piscidin from the hybrid striped bass. AMPs were first assessed against Leishmania major promastigotes using MTS. Subsequently, macrophages were infected with L. major and treated with AMPs to evaluate anti-amastigotes activity of AMPs, and non-infected macrophages were treated with AMPs to determine cytotoxicity against mammalian cells using MTS. The induction of factors limiting L. major growth (IL-12, TNF-α and reactive oxygen species (ROS)) by AMPs was measured by ELISA and dichlorofluorescin-diacetate (DCFH-DA) assay, respectively. Piscidin was more efficacious against L. major promastigotes as compared to dicentracine-like or moronocidin-like peptides, whereas, dicentracine-like and moronocidin-like peptide exhibited a higher activity against L. major amastigotes compared to piscidin. In turn, piscidin was most cytotoxic in non-infected macrophages compared to the other two AMPs. A direct association was observed between hydrophobicity of AMPs and their anti-promastigote and cytotoxic activities. Dicentracine-like or moronocidin-like peptides induced higher levels of IL-12, TNF-α and ROS in macrophages compared to piscidin. Collectively, our results suggest that dicentracine-like and moronocidin-like peptides represent potentially promising multi-functional therapeutic agents that might not only directly kill L. major but also induce anti-Leishmania factors that can limit L. major growth and intracellular survival. Keywords Leishmania · Antimicrobial peptides · Anti-amastigote activity · Anti-promastigote activity · Cytotoxicity
Introduction The genus Leishmania includes several species, which are the causative agents of either cutaneous, mucocutaneous or visceral leishmaniasis in mostly tropical countries (Ansari et al. 2016). More than 350 million people are at risk of infection, 2.4 million disability-adjusted life years (DALYs) Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10989-020-10125-4) contains supplementary material, which is available to authorized users. * Moradali Fouladvand [email protected] Extended author information available on the last p
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