In Silico Predicted Antifungal Peptides: In Vitro and In Vivo Anti-Candida Activity

Ciociola, Tecla; Magliani, Walter; Simone, Tiziano De; Pertinhez, Thelma A.; Conti, Stefania; Cozza, Giorgio; Marin, Oriano; Giovati, Laura

doi:10.3390/jof7060439

Cited by 5 publications

(2 citation statements)

References 35 publications

(44 reference statements)

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“…Antimicrobial peptides seem to be capable of fast killing fungal cells (Ciociola et al, 2021). From the growth curve of C. albicans (Figure 2A), in the absence of C18, C. albicans entered the logarithmic phase within 6 h of incubation and reached stationary phase at 18 h. But the logarithmic phase of C. albicans treated with C18 just only started after 18 h of incubation at the concentration of 2MIC and 4MIC.…”

Section: Growth Inhibition and Killing Kineticsmentioning

confidence: 99%

A Cecropin-4 Derived Peptide C18 Inhibits Candida albicans by Disturbing Mitochondrial Function

et al. 2022

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Global burden of fungal infections and related health risk has accelerated at an incredible pace, and multidrug resistance emergency aggravates the need for the development of new effective strategies. Candida albicans is clinically the most ubiquitous pathogenic fungus that leads to high incidence and mortality in immunocompromised patients. Antimicrobial peptides (AMPs), in this context, represent promising alternatives having potential to be exploited for improving human health. In our previous studies, a Cecropin-4-derived peptide named C18 was found to possess a broader antibacterial spectrum after modification and exhibit significant antifungal activity against C. albicans. In this study, C18 shows antifungal activity against C. albicans or non-albicans Candida species with a minimum inhibitory concentration (MIC) at 4∼32 μg/ml, and clinical isolates of fluconazole (FLZ)-resistance C. tropicalis were highly susceptible to C18 with MIC = 4∼32 μg/ml. Additionally, C18 is superior to FLZ for killing planktonic C. albicans from inhibitory and killing kinetic curves. Moreover, C18 could attenuate the virulence of C. albicans, which includes damaging the cell structure, retarding hyphae transition, and inhibiting biofilm formation. Intriguingly, in the Galleria mellonella model with C. albicans infection, C18 could improve the survival rate of G. mellonella larvae to 70% and reduce C. albicans load from 5.01 × 107 to 5.62 × 104 CFU. For mechanistic action of C18, the level of reactive oxygen species (ROS) generation and cytosolic Ca2 + increased in the presence of C18, which is closely associated with mitochondrial dysfunction. Meanwhile, mitochondrial membrane potential (△Ψm) loss and ATP depletion of C. albicans occurred with the treatment of C18. We hypothesized that C18 might inhibit C. albicans via triggering mitochondrial dysfunction driven by ROS generation and Ca2 + accumulation. Our observation provides a basis for future research to explore the antifungal strategies and presents C18 as an attractive therapeutic candidate to be developed to treat candidiasis.

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Section: Growth Inhibition and Killing Kineticsmentioning

confidence: 99%

A Cecropin-4 Derived Peptide C18 Inhibits Candida albicans by Disturbing Mitochondrial Function

et al. 2022

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“…Bioactivity data can be retrieved from many specialized databases, such as the DBAAPS, APD3, DRAMP, and CAMP databases. Machine learning methods can effectively associate the peptide sequences with their bioactivity values, − and we have proposed many effective algorithms. − However, to the best of our knowledge, few complete works integrate a large-scale screening protocol, successful screening application, chemical synthesis, and bioactivity validation of antifungal peptides.…”

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confidence: 99%

Large-Scale Screening of Antifungal Peptides Based on Quantitative Structure–Activity Relationship

Jin

Yang

Tian

et al. 2021

ACS Med. Chem. Lett.

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Antifungal peptides are effective, biocompatible, and biodegradable, and thus, they are promising to be the next generation of drugs for treating infections caused by fungi. The identification processes of highly active peptides, however, are still time-consuming and labor-intensive. Quantitative structure–activity relationships (QSARs) have dramatically facilitated the discovery of many bioactive drug molecules without a priori knowledge. In this study, we have established an effective QSAR protocol for screening antifungal peptides. The screening protocol integrates an accurate antifungal peptide classification model and four activity prediction models against specified target fungi. A demonstrative application was performed on more than three million candidate peptides, and three outstanding peptides were identified. The whole screening took only a few days, which was much faster than our previous experimental screening works. In conclusion, the protocol is useful and effective for reducing repetitive laboratory efforts in antifungal peptide discovery. The prediction server (antifungal Web server) is freely available at .

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Zika virus precursor membrane peptides induce immune response in peripheral blood mononuclear cells

Gupta,

Baranwal,

Chudasama

2024

Human Immunology

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In Silico Predicted Antifungal Peptides: In Vitro and In Vivo Anti-Candida Activity

Cited by 5 publications

References 35 publications

A Cecropin-4 Derived Peptide C18 Inhibits Candida albicans by Disturbing Mitochondrial Function

A Cecropin-4 Derived Peptide C18 Inhibits Candida albicans by Disturbing Mitochondrial Function

Large-Scale Screening of Antifungal Peptides Based on Quantitative Structure–Activity Relationship

Zika virus precursor membrane peptides induce immune response in peripheral blood mononuclear cells

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