The serine peptidase inhibitor N-ρ-tosyl-l-phenylalanine chloromethyl ketone (TPCK) affects the cell biology of Candida haemulonii species complex

Souto, Xênia Macedo; Ramos, Lívia S.; Oliveira, Simone S. C.; Branquinha, Marta H.; Santos, André Luis Souza dos

doi:10.1016/j.funbio.2020.12.004

Cited by 2 publications

(1 citation statement)

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“…A serine peptidase N-ρ-tosyl-l-phenylalanine chloromethyl ketone (TPCK) inhibitor was also able to alter the integrity of the cell membrane of clinical isolates from Candida spp. by inhibiting the biosynthesis of ergosterol, the main lipid of the composition of the fungal cell membrane [31]. A hypothesis can be raised that the action of drugs based on protease inhibitors, such as TPCK and possibly ShTI, on ergosterol biosynthesis occurs through the inhibition of serine proteases involved in the proteolytic cleavage of the Steroid Regulatory Element Binding Proteins (SREBPs), essential in the regulation of ergosterol biosynthesis genes [32].…”

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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Section: Discussionmentioning

confidence: 99%