Antifungal Effect of A Chimeric Peptide Hn-Mc against Pathogenic Fungal Strains

Kim, Jin‐Young; Park, Seong-Cheol; Noh, Gwangbok; Kim, Heabin; Yoo, Su-Hyang; Kim, Il Ryong; Lee, Jung Ro; Jang, Mi-Kyeong

doi:10.3390/antibiotics9080454

Cited by 9 publications

(8 citation statements)

References 27 publications

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“…The mechanisms of action of numerous AMPs are broadly classified into the following two categories: membranolytic actions such as membrane potential changes and the formation of pores in the cell membrane; and intracellular inhibiting actions such as interfering gene expression, inhibiting enzyme activity, generating reactive oxygen species (ROS), and inducing osmotic pressure [ 28 , 29 ]. There is growing evidence of AMPs inducing cell death by stimulating the production of ROS [ 30 , 31 , 32 , 33 , 34 ]. Although fungal cells repeat the cycle of generating and eliminating intracellular ROS during metabolic pathways, the high levels of ROS damage intracellular lipids, proteins, DNA, organelles, and cell walls [ 35 , 36 ].…”

Section: Resultsmentioning

confidence: 99%

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Antifungal Mechanism of Vip3Aa, a Vegetative Insecticidal Protein, against Pathogenic Fungal Strains

et al. 2021

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Discovering new antifungal agents is difficult, since, unlike bacteria, mammalian and fungal cells are both eukaryotes. An efficient strategy is to consider new antimicrobial proteins that have variety of action mechanisms. In this study, a cDNA encoding Bacillus thuringiensis Vip3Aa protein, a vegetative insecticidal protein, was obtained at the vegetative growth stage; its antifungal activity and mechanism were evaluated using a bacterially expressed recombinant Vip3Aa protein. The Vip3Aa protein demonstrated various concentration- and time-dependent antifungal activities, with inhibitory concentrations against yeast and filamentous fungi ranging from 62.5 to 125 µg/mL and 250 to 500 µg/mL, respectively. The uptake of propidium iodide and cellular distributions of rhodamine-labeled Vip3Aa into fungal cells indicate that its growth inhibition mechanism involves its penetration within cells and subsequent intracellular damage. Furthermore, we discovered that the death of Candida albicans cells was caused by the induction of apoptosis via the generation of mitochondrial reactive oxygen species and binding to nucleic acids. The presence of significantly enlarged Vip3Aa-treated fungal cells indicates that this protein causes intracellular damage. Our findings suggest that Vip3Aa protein has potential applications in the development of natural antimicrobial agents.

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Section: Resultsmentioning

confidence: 99%

“…The inhibitory concentration 50 (IC 50 ) against each fungus was defined as the lowest concentration of a sample that inhibited 50% visible growth. All assays were performed in triplicate [ 30 , 31 , 32 ].…”

Section: Methodsmentioning

confidence: 99%

Antifungal Mechanism of Vip3Aa, a Vegetative Insecticidal Protein, against Pathogenic Fungal Strains

et al. 2021

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“…1-3). The induction of ROS overaccumulation in microorganisms by peptides is not a surprise, but it could explain a lot about the mechanism of action of peptides [11][12][13][14]. ROS is generic to include many molecules such as singlet oxygen ( 1 O2 − ) superoxide anion (•O2 − ), hydroxyl radical (•OH), and hydrogen peroxide (H2O2) [15].…”

Section: Discussionmentioning

confidence: 99%

Behind the Curtain: In silico and in vitro Experiments Brought to Light New Insights Into the Anticryptococcal Action of Synthetic Peptides

Aguiar¹,

Neto²,

Silva³

et al. 2022

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Cryptococcus neoformans threaten the health, causing cryptococcal meningitis and pneumonia, especially in immunosuppressed patients, which can be fatal. Recently, our research group evaluated and studied the mechanisms of action of four synthetic peptides (SP) against C. neoformans. Here, in silico and in vitro analyses help deepen understanding of peptides' mechanisms of action. The interaction of the peptides with a membrane receptor was analyzed by docking analysis, in addition to ROS overproduction and the modulation of redox metabolism, inhibition of ergosterol biosynthesis, and release of cytochrome c. Out of four, three peptides interacted with membrane receptor PHO36 altering its structure and function and leading to a higher accumulation of O₂- and H2O2. C. neoformans cells treated with SP presented a reduction in the activity of antioxidant enzymes, corroborating ROS accumulation. However, in the presence of the antioxidant ascorbic acid, some peptides could not induce this oxidative stress and have the activity against C. neoformans affected. Curiously, two of these SPs still maintained the activity against C. neoformans and even induced the membrane pore formation as revealed by propidium iodide uptake assay, revealing their mechanism of action is ROS-independent. Additionally, SPs inhibited the biosynthesis of ergosterol, which corroborates the pore formation on the membrane of C. neoformans cells, inhibited the lactate dehydrogenase activity affecting the cell metabolism, and induced the release of Cyt c from the mitochondria inducing death by apoptosis in the cryptococcal cells. Our findings strongly suggest that SPs act by multiple mechanisms, making it difficult for C. neoformans to acquire resistance highlighting the potential of SPs as alternative molecules in treating infections caused by C. neoformans.

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“…In this context, these results confirm that chimera arrays are necessary for antifungal activity, since they exhibit a strong effect against C. neoformans var. grubii [ 18 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

In Vitro Antifungal Activity of Chimeric Peptides Derived from Bovine Lactoferricin and Buforin II against Cryptococcus neoformans var. grubii

et al. 2022

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Cryptococcosis is associated with high rates of morbidity and mortality. The limited number of antifungal agents, their toxicity, and the difficulty of these molecules in crossing the blood–brain barrier have made the exploration of new therapeutic candidates against Cryptococcus neoformans a priority task. To optimize the antimicrobial functionality and improve the physicochemical properties of AMPs, chemical strategies include combinations of peptide fragments into one. This study aimed to evaluate the binding of the minimum activity motif of bovine lactoferricin (LfcinB) and buforin II (BFII) against C. neoformans var. grubii. The antifungal activity against these chimeras was evaluated against (i) the reference strain H99, (ii) three Colombian clinical strains, and (iii) eleven mutant strains, with the aim of evaluating the possible antifungal target. We found high activity against these strains, with a MIC between 6.25 and 12.5 µg/mL. Studies were carried out to evaluate the effect of the combination of fluconazole treatments, finding a synergistic effect. Finally, when fibroblast cells were treated with 12.5 µg/mL of the chimeras, a viability of more than 65% was found. The results obtained in this study identify these chimeras as potential antifungal molecules for future therapeutic applications against cryptococcosis.

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Antifungal Effect of A Chimeric Peptide Hn-Mc against Pathogenic Fungal Strains

Cited by 9 publications

References 27 publications

Antifungal Mechanism of Vip3Aa, a Vegetative Insecticidal Protein, against Pathogenic Fungal Strains

Antifungal Mechanism of Vip3Aa, a Vegetative Insecticidal Protein, against Pathogenic Fungal Strains

Behind the Curtain: In silico and in vitro Experiments Brought to Light New Insights Into the Anticryptococcal Action of Synthetic Peptides

In Vitro Antifungal Activity of Chimeric Peptides Derived from Bovine Lactoferricin and Buforin II against Cryptococcus neoformans var. grubii

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