Vol.:(0123456789) 1 3
Archives of Microbiology (2019) 201:223–233
https://doi.org/10.1007/s00203-018-1598-8
ORIGINAL PAPER
Biochemical characterization of a Kunitz inhibitor from Inga edulis
seeds with antifungal activity against Candida spp.
Heloisa Xavier Dib
1
· Daniella Gorete Lourenço de Oliveira
1
· Caio Fernando Ramalho de Oliveira
1
·
Gabriel Bonan Taveira
2
· Erica de Oliveira Mello
2
· Newton Valério Verbisk
3
· Marilene Rodrigues Chang
4
·
Dario Corrêa Junior
4
· Valdirene Moreira Gomes
2
· Maria Lígia Rodrigues Macedo
1
Received: 12 March 2018 / Revised: 3 July 2018 / Accepted: 19 November 2018 / Published online: 27 November 2018
© Springer-Verlag GmbH Germany, part of Springer Nature 2018
Abstract
We describe the characterization of IETI, the frst trypsin inhibitor purifed from Inga edulis, a tree widely distributed in
Brazil. Two-step chromatography was used to purify IETI, a protein composed of a single peptide chain of 19,685.10 Da.
Amino-terminal sequencing revealed that IETI shows homology with the Kunitz family, as substantiated by its physical–
chemical features, such as its thermal (up to 70 °C) and wide-range pH stability (from 2 to 10), and the value of its dissocia-
tion constant (6.2 nM). IETI contains a single reactive site for trypsin, maintained by a disulfde bridge; in the presence of
DTT, its inhibitory activity was reduced in a time- and concentration-dependent manner. IETI presented activity against
Candida ssp., including C. buinensis and C. tropicalis. IETI inhibitory activity triggered yeast membrane permeability,
afecting cell viability, thus providing support for the use of IETI in further studies for the control of fungal infections.
Keywords Trypsin inhibitor · Membrane permeability · Candida tropicalis · Candida buinensis
Introduction
The frst records of fossils indicate the establishment of early
land plants almost 500 million years ago (Heckman et al.
2001). This period was probably followed by frst interac-
tions of plants with microbes and fungi. Although we can
only speculate about subsequent events, the evolution of
plants has triggered molecular interactions with all other
organisms (Chisholm et al. 2006); our current knowledge
about plants shows that several defense-related genes have
emerged to deal with threats to survival and plant perpetua-
tion. These genes encode proteins that include the chitinases,
glucanases, lipid transfer proteins, chitin-binding lectins,
thionins and peptidase inhibitors (Melo et al. 2002), which
present a myriad of biological activities that have been bio-
chemically refned throughout the extensive and constant
process of evolution.
Peptidase inhibitors (PIs) are a group of heterogene-
ous proteins, involved in plant defense against insects and
pathogens, which exert their efects by the inhibition of
peptidases. These proteins are widely distributed in plant
tissues and play dual roles in both defense and storage. The
biological properties of PIs can be mediated by molecular
regions that difer from the protein’s reactive site or via other
mechanisms beyond the formation of the peptidase–inhibi-
tor complex. The wide spectra of biological activities of the
PIs appear to be the consequence of a structural fold that is
shared by some PIs, named the β-trefoil fold (Azarkan et al.
2011).
The Kunitz family of PIs presents the β-trefoil fold and
is currently grouped in the MEROPS database as Family I3
Communicated by Yusuf Akhter.
* Maria Lígia Rodrigues Macedo
ligiamacedo18@gmail.com
1
Laboratório de Purifcação de Proteínas e suas Funções
Biológicas, Faculdade de Ciências de Alimentos e
Nutrição, Universidade Federal do Mato Grosso do Sul,
Campo Grande, MS 79070-900, Brazil
2
Laboratório de Fisiologia e Bioquímica de Microrganismos,
Universidade Estadual do Norte Fluminense,
Campos dos Goytacazes, RJ 28013-600, Brazil
3
Embrapa Gado de Corte, Campo Grande, MS 79106-550,
Brazil
4
Laboratório de Pesquisas Microbiológicas, Faculdade de
Ciências de Alimentos e Nutrição, Universidade Federal
do Mato Grosso do Sul, Campo Grande, MS 79070-900,
Brazil