ClTI, a Kunitz trypsin inhibitor purified from Cassia leiandra Benth. seeds, exerts a candidicidal effect on Candida albicans by inducing oxidative stress and necrosis

Araújo, Nadine Monteiro Salgueiro; Dias, Lucas Pinheiro; Costa, Helen Paula Silva da; Sousa, Daniele O.B.; Vasconcelos, Ilka M.; Morais, Glaucia Almeida de; Oliveira, José T.A.

doi:10.1016/j.bbamem.2019.183032

Cited by 23 publications

(13 citation statements)

References 56 publications

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“…The hydrodynamic radius of calcein, FD4 and FD10 are known to be 0.74, 1.4, and 2.3 nm [ 34 ]. The sizes of the pores formed in the artificial plasma membrane treated with periplanetasin-4 were estimated to range from 1.4 to 2.3 nm [ 35 ]. Such damages, in addition to promoting the leakage of the cytoplasm components, lead to membrane depolarization, loss of membrane functions, homeostasis impairment, and ultimately the loss of cell viability and an imbalance in the intracellular ionic gradient [ 35 ].…”

Section: Resultsmentioning

confidence: 99%

“…The sizes of the pores formed in the artificial plasma membrane treated with periplanetasin-4 were estimated to range from 1.4 to 2.3 nm [ 35 ]. Such damages, in addition to promoting the leakage of the cytoplasm components, lead to membrane depolarization, loss of membrane functions, homeostasis impairment, and ultimately the loss of cell viability and an imbalance in the intracellular ionic gradient [ 35 ]. However, the analogs did not interrupt the liposome and all of the calcein-release values appeared to be similar.…”

Section: Resultsmentioning

confidence: 99%

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Analogs of Periplanetasin-4 Exhibit Deteriorated Membrane-Targeted Action

Lee¹,

Hwang²,

Lee³

2020

Journal of Microbiology and Biotechnology

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Periplanetasin-4 is an antimicrobial peptide with 13 amino acids identified in cockroaches. It has been reported to induce fungal cell death by apoptosis and membrane-targeted action. Analogs were designed by substituting arginine residues to modify the electrostatic and hydrophobic interactions accordingly and explore the effect of periplanetasin-4 through the increase of net charge and the decrease of hydrophobicity. The analogs showed lower activity than periplanetasin-4 against gram-positive and gram-negative bacteria. Similar to periplanetasin-4, the analogs exhibited slight hemolytic activity against human erythrocytes. Membrane studies, including determination of changes in membrane potential and permeability, and fluidity assays, revealed that the analogs disrupt less membrane integrity compared to periplanetasin-4. Likewise, when the analogs were treated to the artificial membrane model, the passage of molecules bigger than FD4 was difficult. In conclusion, arginine substitution could not maintain the membrane disruption ability of periplanetasin-4. The results indicated that the attenuation of hydrophobic interactions with the plasma membrane caused a reduction in the accumulation of the analogs on the membrane before the formation of electrostatic interactions. Our findings will assist in the further development of antimicrobial peptides for clinical use.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Analogs of Periplanetasin-4 Exhibit Deteriorated Membrane-Targeted Action

Lee¹,

Hwang²,

Lee³

2020

Journal of Microbiology and Biotechnology

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“…The results indicated that ShTI did not signi cantly alter cell viability in the MTT test and did not exhibit signs of apoptosis, necrosis, or DNA damage in mouse broblast cells. The literature has reported that plant protease inhibitors were found to be safe in in vitro toxicity assays [25], and there are several preclinical studies on the pharmacological effects of plant protease inhibitors on human health [49]. In addition, chia seeds are widely used as a food ingredient and have not reported cases of toxicity; on the other hand, bene cial effects such as antioxidant [50], antidiabetic and anticholesterol properties [51] associated with the consumption of seed proteins have been described.…”

Section: Discussionmentioning

confidence: 99%

Antifungal activity of a trypsin inhibitor from Salvia hispanica L.(chia) seeds against fluconazole-resistant strains of Candida spp. and evaluation of its toxicity in vitro

Nogueira

Souza

Araújo

et al. 2023

Preprint

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The incidence of Candida species resistance to traditional antifungals is increasing globally. This issue significantly impacts patients' lives and raises healthcare expenses, confirming the need for developing novel therapeutic strategies. Recently, a thermostable trypsin inhibitor was isolated from Salvia hispanica L. (chia) seeds – named ShTI (MM 11.558 kDa) with an antibacterial effect against Staphylococcus aureus species. This work aimed to assess the antifungal effect of ShTI against Candida species and its synergism with fluconazole and to evaluate its mode of action. Moreover, preliminary toxicological studies using mouse fibroblast cells were performed. ShTI displayed an anticandidal effect alone against C. parapsilosis (ATCC® 22019), C. krusei (ATCC® 6258), and six clinical fluconazole-resistant strains of C. albicans (2), C. parapsilosis (2), and C. tropicalis (2) (MIC 50: 4.1 µM and MIC 100: 8.2 µM) and exhibited a synergistic effect when combined with fluconazole against C. albicans with complete alteration of the morphological structure of the yeast. The mode of action of ShTI against C. krusei (ATCC® 6258™) and C. albicans species involves cell membrane damage due to increased membrane permeabilization, overproduction of reactive oxygen species, formation of pseudohyphae, injury of cells and pore formation and consequently cell death. In addition, ShTI (8.65 and 17.3 µM) showed a noncytotoxic and nongenotoxic effect in L929 mouse fibroblast cells. These findings make it plausible to assume that ShTI is a promising antimicrobial candidate, but new assays are required to progress the application of ShTI's potential usage as a novel antifungal.

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“…The role of the Kunitz type trypsin inhibitor from Cassia leiandra seeds ( Cl TI) in the growth inhibition of Candida spp. was presented [ 129 ]. Cl TI anticandidal activity was related not only to the alteration of membrane permeabilization and H + -pump activity, but also to the induction of oxidative stress and DNA damage, suggesting the involvement of apoptotic and necrotic mechanisms.…”

Section: A New Perspective For Plants’ Components In Antifungal Thmentioning

confidence: 99%

Plant-Derived Substances in the Fight Against Infections Caused by Candida Species

Guevara-Lora

Bras

Karkowska‐Kuleta

et al. 2020

IJMS

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Yeast-like fungi from the Candida genus are predominantly harmless commensals that colonize human skin and mucosal surfaces, but under conditions of impaired host immune system change into dangerous pathogens. The pathogenicity of these fungi is typically accompanied by increased adhesion and formation of complex biofilms, making candidal infections challenging to treat. Although a variety of antifungal drugs have been developed that preferably attack the fungal cell wall and plasma membrane, these pathogens have acquired novel defense mechanisms that make them resistant to standard treatment. This causes an increase in the incidence of candidiasis and enforces the urgent need for an intensified search for new specifics that could be helpful, alone or synergistically with traditional drugs, for controlling Candida pathogenicity. Currently, numerous reports have indicated the effectiveness of plant metabolites as potent antifungal agents. These substances have been shown to inhibit growth and to alter the virulence of different Candida species in both the planktonic and hyphal form and during the biofilm formation. This review focuses on the most recent findings that provide evidence of decreasing candidal pathogenicity by different substances of plant origin, with a special emphasis on the mechanisms of their action. This is a particularly important issue in the light of the currently increasing frequency of emerging Candida strains and species resistant to standard antifungal treatment.

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ClTI, a Kunitz trypsin inhibitor purified from Cassia leiandra Benth. seeds, exerts a candidicidal effect on Candida albicans by inducing oxidative stress and necrosis

Cited by 23 publications

References 56 publications

Analogs of Periplanetasin-4 Exhibit Deteriorated Membrane-Targeted Action

Analogs of Periplanetasin-4 Exhibit Deteriorated Membrane-Targeted Action

Antifungal activity of a trypsin inhibitor from Salvia hispanica L.(chia) seeds against fluconazole-resistant strains of Candida spp. and evaluation of its toxicity in vitro

Plant-Derived Substances in the Fight Against Infections Caused by Candida Species

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