Novel antimicrobial peptide DvAMP serves as a promising antifungal agent against Cryptococcus neoformans

Yang, Longbing; Tian, Zhuqing; Zhao, Wenjing; Jin, Zhang; Tian, Chunren; Zhou, Lifeng; Jiao, Zhenlong; Peng, Jian; Guo, Guo

doi:10.1016/j.bioorg.2023.106679

Cited by 5 publications

(5 citation statements)

References 61 publications

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“…Currently reported antimicrobial peptides (AMPs) with anti-C. neoformans activity include DvAMP [69], PrAMP [70], and AMP-17 [71], and their MIC values are higher than 1 µM against this fungal pathogen. In contrast, the antimicrobial peptide blap-6 identified in this study has a MIC of 0.81 µM against C. neoformans.…”

Section: Discussionmentioning

confidence: 99%

Blap-6, a Novel Antifungal Peptide from the Chinese Medicinal Beetle Blaps rhynchopetera against Cryptococcus neoformans

Zhang,

Zhou,

Huang

et al. 2024

IJMS

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Cryptococcus neoformans (C. neoformans) is a pathogenic fungus that can cause life-threatening meningitis, particularly in individuals with compromised immune systems. The current standard treatment involves the combination of amphotericin B and azole drugs, but this regimen often leads to inevitable toxicity in patients. Therefore, there is an urgent need to develop new antifungal drugs with improved safety profiles. We screened antimicrobial peptides from the hemolymph transcriptome of Blaps rhynchopetera (B. rhynchopetera), a folk Chinese medicine. We found an antimicrobial peptide named blap-6 that exhibited potent activity against bacteria and fungi. Blap-6 is composed of 17 amino acids (KRCRFRIYRWGFPRRRF), and it has excellent antifungal activity against C. neoformans, with a minimum inhibitory concentration (MIC) of 0.81 μM. Blap-6 exhibits strong antifungal kinetic characteristics. Mechanistic studies revealed that blap-6 exerts its antifungal activity by penetrating and disrupting the integrity of the fungal cell membrane. In addition to its direct antifungal effect, blap-6 showed strong biofilm inhibition and scavenging activity. Notably, the peptide exhibited low hemolytic and cytotoxicity to human cells and may be a potential candidate antimicrobial drug for fungal infection caused by C. neoformans.

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Section: Discussionmentioning

confidence: 99%

Blap-6, a Novel Antifungal Peptide from the Chinese Medicinal Beetle Blaps rhynchopetera against Cryptococcus neoformans

Zhang,

Zhou,

Huang

et al. 2024

IJMS

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“…G. mellonella has been used to study many fungi, including Aspergillus spp., Candida spp., Cryptococcus spp., Conidiobolus coronatus , Histoplasma capsulatum , Madurella mycetomatis , Malassezia spp. and Paraccocidioides brasiliensis [ 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 ].…”

Section: G Mellonella As a Model To Study Fungi In Vivomentioning

confidence: 99%

“…Categorising studies using G. mellonella larvae to assess virulence or drug efficacy is a challenging task. It is more appropriate to evaluate the work based on different fungal genera since some species have undergone extensive research in recent years [ 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 ].…”

Section: G Mellonella As a Model To Study Fungi In Vivomentioning

confidence: 99%

“…In comparison to ITR alone, the combination of HCQ and ITR treatment increased the survival of larvae while decreasing the fungal burden of infected larvae [ 89 ]. An antimicrobial peptide with 100% homology to Drosophila virilis (DvAMP) has significant in vivo therapeutic effects on G. mellonella larvae since it reduces mortality and fungal load in C. neoformans larvae, suggesting that this peptide may be a promising antifungal candidate for the treatment of cryptococcosis [ 90 ]. Similar results were also reported using vitamin D3 (VD3) [ 91 ].…”

Section: G Mellonella As a Model To Study Fungi In Vivomentioning

confidence: 99%

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Galleria mellonella as a Model for the Study of Fungal Pathogens: Advantages and Disadvantages

Giammarino,

Bellucci,

Angiolella

2024

Pathogens

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The study of pathogenicity and virulence of fungal strains, in vivo in the preclinical phase, is carried out through the use of animal models belonging to various classes of mammals (rodents, leproids, etc.). Although animals are functionally more similar to humans, these studies have some limitations in terms of ethics (animal suffering), user-friendliness, cost-effectiveness, timing (physiological response time) and logistics (need for adequately equipped laboratories). A good in vivo model must possess some optimal characteristics to be used, such as rapid growth, small size and short life cycle. For this reason, insects, such as Galleria mellonella (Lepidoptera), Drosophila melanogaster (Diptera) and Bombyx mori (Lepidoptera), have been widely used as alternative non-mammalian models. Due to their simplicity of use and low cost, the larvae of G. mellonella represent an optimal model above all to evaluate the virulence of fungal pathogens and the use of antifungal treatments (either single or in combination with biologically active compounds). A further advantage is also represented by their simple neuronal system limiting the suffering of the animal itself, their ability to survive at near-body ambient temperatures as well as the expression of proteins able to recognise combined pathogens following the three R principles (replacement, refinement and reduction). This review aims to assess the validity as well as the advantages and disadvantages of replacing mammalian classes with G. mellonella as an in vivo study model for preclinical experimentation.

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“…13,14 Experimental validation has confirmed the effectiveness of AFI: among 16 synthesized AFPs, 50% exhibited antifungal activity by inhibiting at least one of the four tested fungi species (Candida albicans SC5314, Candida krusei IFM56881, Cryptococcosis neoformans H99, and Candida parapsilosis ATCC22019) at a minimum inhibitory concentration (MIC) below 32 μM. 15 Leveraging AFI, we have recently designed and synthesized two novel AFPs, named DvAMP 16,17 and MR-22 18 showing remarkable antifungal, antimicrobial, and antibiofilm capabilities, and outperformed others in models of C. neoformans H99-infected Galleria mellonella, carbapenem-resistant Acinetobacter baumannii-infected mouse pneumonia, and multidrug-resistant Escherichia coli-infected mouse peritonitis. Collectively, these studies highlight the potential of the AFI as a quantitative and reliable index for AFP design.…”

Section: Introductionmentioning

confidence: 96%

In Silico Design and Synthesis of Antifungal Peptides Guided by Quantitative Antifungal Activity

Zhang,

Sun,

Zhao

et al. 2024

J. Chem. Inf. Model.

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Antifungal peptides (AFPs) are emerging as promising candidates for advanced antifungal therapies because of their broad-spectrum efficacy and reduced resistance development. In silico design of AFPs, however, remains challenging, due to the lack of an efficient and well-validated quantitative assessment of antifungal activity. This study introduced an AFP design approach that leverages an innovative quantitative metric, named the antifungal index (AFI), through a three-step process, i.e., segmentation, single-point mutation, and global multipoint optimization. An exhaustive search of 100 putative AFP sequences indicated that random modifications without guidance only have a 5.97–20.24% chance of enhancing antifungal activity. Analysis of the search results revealed that (1) N-terminus truncation is more effective in enhancing antifungal activity than the modifications at the C-terminus or both ends, (2) introducing the amino acids within the 10–60% sequence region that enhance aromaticity and hydrophobicity are more effective in increasing antifungal efficacy, and (3) incorporating alanine, cysteine, and phenylalanine during multiple point mutations has a synergistic effect on enhancing antifungal activity. Subsequently, 28 designed peptides were synthesized and tested against four typical fungal strains. The success rate for developing promising AFPs, with a minimal inhibitory concentration of ≤5.00 μM, was an impressive 82.14%. The predictive and design tool is accessible at .

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Novel antimicrobial peptide DvAMP serves as a promising antifungal agent against Cryptococcus neoformans

Cited by 5 publications

References 61 publications

Blap-6, a Novel Antifungal Peptide from the Chinese Medicinal Beetle Blaps rhynchopetera against Cryptococcus neoformans

Blap-6, a Novel Antifungal Peptide from the Chinese Medicinal Beetle Blaps rhynchopetera against Cryptococcus neoformans

Galleria mellonella as a Model for the Study of Fungal Pathogens: Advantages and Disadvantages

In Silico Design and Synthesis of Antifungal Peptides Guided by Quantitative Antifungal Activity

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