EBAMP: An efficient de novo broad-spectrum antimicrobial peptide discovery framework
De novo design of antimicrobial peptides (AMPs) is challenging due to the vast combinatorial space and unknown mechanisms. We propose EBAMP, a generative-discriminative framework for de novo broad-spectrum AMP design targeting bacteria and fungi. EBAMP combines a Transformer-based generative model with advanced feature-based screening to explore peptide space and select multiobjective candidates. Experimental testing of 256 designed sequences shows that 96 (37.5%) display bactericidal ability. The top 10 sequences exhibit low cytotoxicity, low hemolysis, and strong antibacterial effect (2 μg/mL) against multidrug-resistant bacteria and fungi. In vivo mouse full-thickness wound infection model demonstrates inhibitory effects against Acinetobacter baumannii (bacterium) and Candida auris (fungus), with therapeutic efficiency comparable to antibiotics but lower resistance propensity. Alanine substitution analysis and molecular dynamics reveal functionally critical positions. EBAMP showcases large generative models for broad-spectrum AMP discovery and addresses antibiotic resistance.
Authors
- Wenhua Huang (ORCID: https://orcid.org/0000-0003-2382-9180)
- Zili Chai (ORCID: https://orcid.org/0000-0003-3399-6281)
- Xinxin Su (ORCID: https://orcid.org/0000-0002-9417-3636)
- Yixin Su (ORCID: https://orcid.org/0000-0002-3143-3939)
- Dongsheng Li (ORCID: https://orcid.org/0000-0001-8232-5041)
- Yutao Dou (ORCID: https://orcid.org/0000-0001-9990-690X)
- Yuhao Ren (ORCID: https://orcid.org/0000-0002-0983-8681)
- Hongguang Ren (ORCID: https://orcid.org/0000-0002-9151-6090)
- Yao Ding (ORCID: https://orcid.org/0000-0003-2040-2640)
- Pengpeng Liu (ORCID: https://orcid.org/0000-0001-6515-4682)
- Xinran Zhang (ORCID: https://orcid.org/0000-0002-2017-3182)
- Qian Li (ORCID: https://orcid.org/0000-0003-4963-8331)
- Qiang Zhang (ORCID: https://orcid.org/0000-0001-6520-2525)
- Yida David Hu (ORCID: https://orcid.org/0000-0001-5666-4381)
- Boqian Wang (ORCID: https://orcid.org/0000-0003-3244-4450)
- Yuan Jin
- Yongqiang Jiang
- Zhen Huang (ORCID: https://orcid.org/0000-0003-3393-1859)
- Haoran Yu (ORCID: https://orcid.org/0009-0006-4229-0976)
- Mingguang Sun
- Ling Jiang (ORCID: https://orcid.org/0009-0004-1072-3461)
Institutions
- Hunan University (CN)
- National University of Defense Technology (CN)
- Anhui Medical University (CN)
- Academy of Military Medical Sciences (CN)
- Czech Academy of Sciences, Institute of Biotechnology (CZ)
- Zhejiang Lab (CN)
- Zhejiang University-University of Edinburgh Institute (CN)
- Huazhong University of Science and Technology (CN)
- Zhejiang University of Technology (CN)
- University of Defence (CZ)
Publication Details
- Journal
- Cell Reports
- Published
- 2025-09-01
- DOI
- https://doi.org/10.1016/j.celrep.2025.116215
- Citations
- 6
- Primary Topic
- Antimicrobial Peptides and Activities
- Type
- article
- Field-Weighted Citation Impact
- 7.10