Enhancement of the Antifungal Activity of Chitinase by Palmitoylation and the Synergy of Palmitoylated Chitinase with Amphotericin B

Santoso, Pugoh; Minamihata, Kosuke; Ishimine, Yugo; Taniguchi, Hiromasa; Komada, Takuya; Sato, Ryo; Goto, Masahiro; Takashima, Tomoya; Taira, Toki; Kamiya, Noriho

doi:10.1021/acsinfecdis.2c00052

Cited by 13 publications

(18 citation statements)

References 42 publications

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“…The cytotoxicity against mammalian cells did not change by anchoring LysM-Pal on AmBisome, suggesting that the state of AmB in AmBisome was not significantly altered by anchoring LysM-Pal. In our previous report, we confirmed that 1 μM LysM-Pal with 5 μM Fungizone, micellar formulation of amphotericin B solubilized with sodium deoxycholate and is more cytotoxic than AmBisome, did not show cytotoxicity against mammalian cells . Moreover, we have evaluated the cytotoxicity of various lipidated EGFP against SNU-6 cells at a concentration of 1 μM and all lipids including C16 showed no cytotoxicity .…”

Section: Resultssupporting

confidence: 67%

“…In our previous report, we confirmed that 1 μM LysM-Pal with 5 μM Fungizone, micellar formulation of amphotericin B solubilized with sodium deoxycholate and is more cytotoxic than AmBisome, did not show cytotoxicity against mammalian cells. 28 Moreover, we have evaluated the cytotoxicity of various lipidated EGFP against SNU-6 cells at a concentration of 1 μM and all lipids including C16 showed no cytotoxicity. 27 These results indicate that LysM-AmBisome may not show adverse effects on mammalian cells and can be used in the same way as AmBisome.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…The LysM domain modified with a palmitoyl group at the C-terminus (LysM-Pal) was prepared by recently developed microbial transglutaminase (MTG)-mediated protein lipidation, and then mixed with AmBisome (Figure ). In our recent work, the LysM-Pal exhibited synergistic enhancement of antifungal activity when it was combined with Fungizone . The selection of an appropriate targeting unit represents the key step to enhance the clinical relevance of AmBisome.…”

Section: Introductionmentioning

confidence: 98%

“…In our recent work, the LysM-Pal exhibited synergistic enhancement of antifungal activity when it was combined with Fungizone. 28 The selection of an appropriate targeting unit represents the key step to enhance the clinical relevance of AmBisome. We anticipated that LysM-Pal anchors its palmitic acid motif to the lipid bilayer of AmBisome and facilitates targeting AmBisome to fungi.…”

Section: ■ Introductionmentioning

confidence: 99%

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Liposomal Amphotericin B Formulation Displaying Lipid-Modified Chitin-Binding Domains with Enhanced Antifungal Activity

et al. 2022

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Fungal infections affect more than one billion people worldwide and cause more than one million deaths per year. Amphotericin B (AmB), a polyene antifungal drug, has been used as the gold standard for many years because of its broad antifungal spectrum, high activity, and low tendency of drug resistance. However, the side effects of AmB, such as nephrotoxicity and hepatotoxicity, have hampered its widespread use, leading to the development of a liposome-type AmB formulation, AmBisome. Herein, we report a simple but highly effective strategy to enhance the antifungal activity of AmBisome with a lipid-modified protein.The chitin-binding domain (LysM) of the antifungal chitinase, Pteris ryukyuensis chitinase A (PrChiA), a small 5.3 kDa protein that binds to fungal cell wall chitin, was engineered to have a glutamine-containing peptide tag at the C-terminus for the microbial transglutaminase (MTG)-catalyzed crosslinking reaction (LysM-Q). LysM-Q was site-specifically modified with a lysine-containing lipid peptide substrate of MTG with a palmitoyl moiety (Pal-K). The resulting palmitoylated LysM (LysM-Pal) exhibited negligible cytotoxicity to mammalian cells and can be easily anchored to yield LysM-presenting AmBisome (LysM-AmBisome). LysM-AmBisome exhibited a dramatic enhancement of antifungal activity toward Trichoderma viride and Cryptococcus neoformans, demonstrating the marked impact of displaying a cell-wall binder protein on the targeting ability of antifungal liposomal formulations. Our simple strategy with enzymatic protein lipidation provides a potent approach to upgrade other types of lipid-based drug formulations.

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Section: Resultssupporting

confidence: 67%

Section: ■ Results and Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Section: ■ Introductionmentioning

confidence: 99%

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Liposomal Amphotericin B Formulation Displaying Lipid-Modified Chitin-Binding Domains with Enhanced Antifungal Activity

et al. 2022

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“…These results suggest that dipicolinic acid can be a suitable complement to reduce the concentration and use of carbendazim. These results can be explained considering that dipicolinic acid is capable of damaging F. sulawense cell wall, which may facilitate the entry of carbendazim inside the pathogen cells [ 67 ]. As far as we know, this is the first study regarding the combination of carbendazim and dipicolinic acid for the control of fungal diseases.…”

Section: Discussionmentioning

confidence: 99%

Identification of New Fusarium sulawense Strains Causing Soybean Pod Blight in China and Their Control Using Carbendazim, Dipicolinic Acid and Kojic Acid

Sun

Zhang

Xie

et al. 2022

IJERPH

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Soybean plants are highly susceptible to Fusarium species, which significantly reduce soybean production and quality. Several Fusarium species have been reported to synthesize mycotoxins, such as trichothecene, which have been related to major human diseases. In November 2021, soybean pods in Nantong municipality, China, showed black necrotic lesions during the harvest stage. The disease incidence reached 69%. The pathogen was identified as Fusarium sulawense via morphological analysis and sequencing of ITS, EF1-α and RPB2 genes. A PCR assay with primers targeting the trichothecene biosynthesis genes suggested that the three isolates could synthesize trichothecenes. The effectiveness of fungicide carbendazim and natural metabolites dipicolinic acid and kojic acid was screened for the management of F. sulawense on postharvest soybean pods. The highest efficacy was obtained when combining 3.8 mg/mL carbendazim and 0.84 mg/mL dipicolinic acid (curative efficacy: 49.1% lesion length inhibition; preventive efficacy: 82.7% lesion length inhibition), or 1.9 mg/mL carbendazim and 0.71 mg/mL kojic acid (preventive efficacy: 84.9% lesion length inhibition). Collectively, this report will lead to a better understanding of the safety hazards found in soybean products in China and reveals the application of dipicolinic and kojic acids to reduce the use of carbendazim.

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Overexpression of the chimeric chitinase (ChBD) gene in Lycopersicon esculentum L. enhanced resistance to Sclerotinia sclerotiorum

Gougerdchi

Dorani²,

Valizadeh³

et al. 2022

Plant Cell Tiss Organ Cult

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Enhancement of the Antifungal Activity of Chitinase by Palmitoylation and the Synergy of Palmitoylated Chitinase with Amphotericin B

Cited by 13 publications

References 42 publications

Liposomal Amphotericin B Formulation Displaying Lipid-Modified Chitin-Binding Domains with Enhanced Antifungal Activity

Liposomal Amphotericin B Formulation Displaying Lipid-Modified Chitin-Binding Domains with Enhanced Antifungal Activity

Identification of New Fusarium sulawense Strains Causing Soybean Pod Blight in China and Their Control Using Carbendazim, Dipicolinic Acid and Kojic Acid

Overexpression of the chimeric chitinase (ChBD) gene in Lycopersicon esculentum L. enhanced resistance to Sclerotinia sclerotiorum

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