A recombinant fungal defensin-like peptide-P2 combats multidrug-resistant Staphylococcus aureus and biofilms

Yang, Na; Teng, Da; Mao, Ruoyu; Hao, Ya; Wang, Xiao; Wang, Zhenlong; Wang, Xiumin; Wang, Jianhua

doi:10.1007/s00253-019-09785-0

Cited by 54 publications

(85 citation statements)

References 63 publications

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“…The MIC value is a key factor in preliminary screening of candidate peptides, for which ≤16 µg/mL or ≤16 µmol/L has been posed as a requirement in clinical studies (Barreto-Santamaria et al, 2019). In this study, compared with DLP4, ID13 had a lower MIC value (4∼8 µg/mL), hemolytic activity (0.38%), and cytotoxicity (71.4% viability) ( Table 2 and Figure 2), which may be related to the different α-helix content between peptide ID13 and DLP4 in bacterial membrane mimicking (40 mM SDS) and neutral membrane conditions (50% TFE) (Figure 3; Yang et al, 2019); the higher α-helix content of peptides indicates the stronger affinity of peptide to cell membranes and thus more potent activity and toxicity (Barreto-Santamaria et al, 2019). An increase in total hydrophobicity in a certain range also increased the antibacterial activity of ID13 ( Table 1).…”

Section: Discussionmentioning

confidence: 70%

“…S. aureus CVCC 546 cells in the exponential phase (10 8 CFU/mL) were treated with 4 × MIC peptides at 37 • C for 2 h or left untreated as control. Cells for SEM or TEM were processed as described previously (Yang et al, 2019) and samples were observed using a QUANTA 200 SEM (FEI, Philips, Netherlands) or a JEM-1400 (JEDL, Tokyo, Japan).…”

Section: Morphological Observationsmentioning

confidence: 99%

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An Enhanced Variant Designed From DLP4 Cationic Peptide Against Staphylococcus aureus CVCC 546

Yang

Wang

et al. 2020

Front. Microbiol.

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Insect defensins are promising candidates for the development of potent antimicrobials against antibiotic-resistant Staphylococcus aureus (S. aureus). An insect defensin, DLP4, isolated from the hemolymph of Hermetia illucens larvae, showed low antimicrobial activity against Gram-positive (G +) pathogens and high cytotoxicity, which limited its effective therapeutic application. To obtain more potent and low cytotoxicity molecules, a series of peptides was designed based on the DLP4 template by changing the conservative site, secondary structure, charge, or hydrophobicity. Among them, a variant designated as ID13 exhibited strong antibacterial activity at low MIC values of 4-8 µg/mL to G + pathogens (S. aureus: 4 µg/mL; Staphylococcus epidermidis: 8 µg/mL; Streptococcus pneumoniae: 4 µg/mL; Streptococcus suis: 4 µg/mL), which were lower than those of DLP4 (S. aureus: 16 µg/mL; S. epidermidis: 64 µg/mL; S. pneumoniae: 32 µg/mL; S. suis: 16 µg/mL), and cytotoxicity of ID13 (71.4% viability) was less than that of DLP4 (63.8% viability). ID13 could penetrate and destroy the cell membrane of S. aureus CVCC 546, resulting in an increase in potassium ion leakage; it bound to genomic DNA (gDNA) and led to the change of gDNA conformation. After treatment with ID13, perforated, wrinkled, and collapsed S. aureus CVCC 546 cells were observed in electron microscopy. Additionally, ID13 killed over 99.99% of S. aureus within 1 h, 2 × MIC of ID13 induced a post-antibiotic effect (PAE) of 12.78 ± 0.28 h, and 10 mg/kg ID13 caused a 1.8 log 10 (CFU/g) (CFU: colony-forming units) reduction of S. aureus in infected mouse thigh muscles and a downregulation of TNF-α, IL-6, and IL-10 levels, which were superior to those of DLP4 or vancomycin. These findings indicate that ID13 may be a promising peptide antimicrobial agent for therapeutic application.

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Section: Discussionmentioning

confidence: 70%

Section: Morphological Observationsmentioning

confidence: 99%

An Enhanced Variant Designed From DLP4 Cationic Peptide Against Staphylococcus aureus CVCC 546

Yang

Wang

et al. 2020

Front. Microbiol.

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“…Recently, Yang et al [32] have characterized nine fungal defensin-like peptides (peptides synthesized by neutrophils with antimicrobial and cytotoxic properties) as potent antibacterial compounds. This team expressed them in Pichia pastoris and tested their antibacterial and anti-biofilm abilities against MDR and persistent S. aureus.…”

Section: Antimicrobial Peptides (Amps)mentioning

confidence: 99%

Strategies to Combat Persistent Infectious Diseases

Pacios¹,

Blasco²,

Bleriot³

et al. 2019

Preprint

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Antibiotic failure is one of the most worrying health problems worldwide. Nowadays we are facing an international crisis where several issues are involved: new antibiotics are not being discovered any longer, resistance mechanisms become spread in nearly every clinical isolate of bacteria and the appearance of recurrent infections caused by persistent bacteria complicates the overcoming of infections. In this context, it has been explored new anti-infectious strategies against MDR and persistent bacteria as well as the rescue of FDA-approved compounds (drug repurposing). Among the highlighted new anti-infectious strategies we find anti-microbial peptides, anti-virulence compounds, phage therapy and new molecules. On the other hand, as drugs of repurposing that have been described, we have anti-inflammatory compounds, anti-psychotics, anti-helmintic drugs, anti-cancerous and statins.

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“…In a recent study, Yang and colleagues characterized nine fungal defensin-like peptides, i.e., peptides synthesized by neutrophils with antimicrobial and cytotoxic properties, and identified them as potent antibacterial compounds [31]. The peptides were expressed in Pichia pastoris, and their antibacterial and anti-biofilm activities against MDR and persistent S. aureus were evaluated.…”

Section: Antimicrobial Peptides (Amps)mentioning

confidence: 99%

Strategies to Combat Multidrug-Resistant and Persistent Infectious Diseases

et al. 2020

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Antibiotic failure is one of the most worrying health problems worldwide. We are currently facing an international crisis with several problematic facets: new antibiotics are no longer being discovered, resistance mechanisms are occurring in almost all clinical isolates of bacteria, and recurrent infections caused by persistent bacteria are hampering the successful treatment of infections. In this context, new anti-infectious strategies against multidrug-resistant (MDR) and persistent bacteria, as well as the rescue of Food and Drug Administration (FDA)-approved compounds (drug repurposing), are being explored. Among the highlighted new anti-infectious strategies, in this review, we focus on antimicrobial peptides, anti-virulence compounds, phage therapy, and new molecules. As drugs that are being repurposed, we highlight anti-inflammatory compounds, anti-psychotics, anti-helminthics, anti-cancerous drugs, and statins.

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A recombinant fungal defensin-like peptide-P2 combats multidrug-resistant Staphylococcus aureus and biofilms

Cited by 54 publications

References 63 publications

An Enhanced Variant Designed From DLP4 Cationic Peptide Against Staphylococcus aureus CVCC 546

An Enhanced Variant Designed From DLP4 Cationic Peptide Against Staphylococcus aureus CVCC 546

Strategies to Combat Persistent Infectious Diseases

Strategies to Combat Multidrug-Resistant and Persistent Infectious Diseases

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