Related Experiment Video
Updated: Dec 31, 2025
Application of I TASSER, trRosetta, UCSF Chimera, HADDOCK server, and HEX loria for De Novo and In Silico Design of Proteins
Published on: July 8, 2025
Design of Heptad Repeat Amphiphiles Based on Database Filtering and Structure-Function Relationships to Combat
Peng Tan1, Zhenheng Lai1, Qiao Jian1
1Laboratory of Molecular Nutrition and Immunity, The Institute of Animal Nutrition , Northeast Agricultural University , Harbin 150030 , China.
Abstract:
Due to the emergence of reports of multidrug-resistant fungi, infections caused by multidrug-resistant fungi and biofilms are considered to be a global threat to human health due to the lack of effective broad-spectrum drugs. Here, we developed a series heptad repeat sequences based on an antimicrobial peptide database (APD) and structure-function relationships. Among the developed peptides, the target peptide ACR3 exhibited good activity against all fungi and bacteria tested, including fluconazole-resistant Candida albicans (C. albicans) and methicillin-resistant Staphylococcu saureus (S. aureus), while demonstrating relatively low toxicity and good salt tolerance. The peptide ACR3 inhibits the formation of C. albicans biofilms and has a therapeutic effect on mature biofilms in vitro and in vivo. Moreover, we did not observe any resistance of C. albicans and E. coli against the peptide ACR3. A series of assays and microscopy were used to analyze the antimicrobial mechanism. These results showed that the antimicrobial activity of the peptide ACR3 utilizes a multimodal mechanism that degrades the cell wall barrier, alters the cytoplasmic membrane electrical potential, and induces intracellular reactive oxygen species (ROS) production. In general, the peptide ACR3 is a potent antibacterial agent that shows great potential for use in biomedical coatings and healthcare formulas to combat the growing threat of fungal and bacterial infection.
Insights
A novel peptide, ACR3, effectively combats multidrug-resistant fungi and bacteria, including biofilms. It shows low toxicity and no observed resistance, offering potential for new healthcare applications.
Area of Science:
- Microbiology
- Biochemistry
- Drug Discovery
Background:
- Multidrug-resistant fungi and bacteria pose a significant global health threat due to limited effective treatments.
- Antimicrobial peptides (AMPs) are a promising area for developing new broad-spectrum antimicrobial agents.
Purpose of the Study:
- To design and evaluate novel heptad repeat sequence-based peptides with antimicrobial activity.
- To investigate the efficacy, safety, and mechanism of action of the lead peptide candidate, ACR3.
Main Methods:
- Peptide design based on an antimicrobial peptide database (APD) and structure-function analysis.
- Antimicrobial susceptibility testing against various fungal and bacterial strains, including resistant isolates.
- Assessment of peptide toxicity, salt tolerance, and biofilm inhibition/treatment capabilities.
- In vitro and in vivo studies to evaluate therapeutic effects.
- Mechanism of action studies using assays and microscopy to analyze cell wall degradation, membrane potential, and ROS production.
Main Results:
- Peptide ACR3 demonstrated broad-spectrum activity against tested fungi and bacteria, including fluconazole-resistant Candida albicans and methicillin-resistant Staphylococcus aureus.
- ACR3 exhibited low toxicity and good salt tolerance.
- The peptide effectively inhibited Candida albicans biofilm formation and treated mature biofilms both in vitro and in vivo.
- No resistance was observed in Candida albicans and E. coli against ACR3.
- ACR3 employs a multimodal mechanism involving cell wall degradation, altered cytoplasmic membrane potential, and induced reactive oxygen species (ROS) production.
Conclusions:
- Peptide ACR3 is a potent antimicrobial agent with significant potential against multidrug-resistant pathogens.
- Its multimodal mechanism and lack of observed resistance suggest it could be a valuable therapeutic option.
- ACR3 shows promise for applications in biomedical coatings and healthcare formulations to combat infectious diseases.
More Related Videos
Related Concept Videos
01:28Structure-Activity Relationships and Drug Design
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...
01:29Biofilms