ClCPI, a cysteine protease inhibitor purified from Cassia leiandra seeds has antifungal activity against Candida tropicalis by inducing disruption of the cell surface

Infections caused by Candida tropicalis have increased significantly worldwide in parallel with resistance to antifungal drugs. To overcome resistance novel drugs have to be discovered. The objective of this work was to purify and characterize a cysteine protease inhibitor from the seeds of the Amaz...

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Bibliographic Details
Published in:	International journal of biological macromolecules 2019-07, Vol.133, p.1115-1124
Main Authors:	Melo, Ivna R.S., Dias, Lucas P., Araújo, Nadine M.S., Vasconcelos, Ilka M., Martins, Thiago F., de Morais, Glaucia A., Gonçalves, Jose F.C., Nagano, Celso S., Carneiro, Rômulo F., Oliveira, Jose T.A.
Format:	Article
Language:	eng
Subjects:	Antifungal Candida tropicalis Cassia leiandra Cysteine inhibitor
Online Access:	Get full text
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Summary:	Infections caused by Candida tropicalis have increased significantly worldwide in parallel with resistance to antifungal drugs. To overcome resistance novel drugs have to be discovered. The objective of this work was to purify and characterize a cysteine protease inhibitor from the seeds of the Amazon rainforest tree Cassia leiandra and test its inhibitory effect against C. tropicalis growth. The inhibitor, named ClCPI, was purified after ion exchange and affinity chromatography followed by ultrafiltration. ClCPI is composed of a single polypeptide chain and is not a glycoprotein. The molecular mass determined by SDS-PAGE in the absence or presence of β-mercaptoethanol and ESI-MS were 16.63 kDa and 18.362 kDa, respectively. ClCPI was stable in the pH range of 7.0–9.0 and thermostable up to 60 °C for 20 min. ClCPI inhibited cysteine proteases, but not trypsin, chymotrypsin neither alpha-amylase. Inhibition of papain was uncompetitive with a Ki of 4.1 × 10−7 M and IC50 of 8.5 × 10−7 M. ClCPI at 2.6 × 10−6 M reduced 50% C. tropicalis growth. ClCPI induced damages and morphological alterations in C. tropicalis cell surface, which led to death. These results suggest that ClCPI have great potential for the development of an antifungal drug against C. tropicalis. •ClCPI is a cysteine protease inhibitor purified from Cassia leiandra seeds.•ClCPI is composed of a 16.63 kDa single polypeptide chain.•ClCPI has antifungal activity against Candida tropicalis.•ClCPI causes damage in the Candida tropicalis cell surface.•ClCPI has great potential as an antifungal drug against C. tropicalis.
ISSN:	0141-8130 1879-0003