Loading…
Antimicrobial resistance threatens public health, driving the need for alternative therapies like antimicrobial peptides (AMPs). Protein language models (PLMs) enhance protein structure and function predictions, aiding AMP discovery. We created the antimicrobial peptide structural evolution miner (AMP-SEMiner), an AI framework that combines PLMs, structural clustering, and evolutionary analysis to identify AMPs from small open reading frames and AMP-containing proteins in metagenome-assembled genomes. AMP-SEMiner found over 1.6 million AMP candidates in various environments. Experiments confirmed antimicrobial activity in 9 of the 20 tested candidates, with 5 outperforming antibiotics; variant peptides from these candidates also showed strong antimicrobial effects. AMPs from human gut microbiomes displayed both conserved and adaptive evolutionary strategies, highlighting their ecological roles. AMP-SEMiner is a valuable tool for expanding AMP discovery and can significantly inform the development of alternative antimicrobial treatments.
Antimicrobial peptides (AMPs) are promising candidates for therapeutic use and have been clinically applied as antiviral drugs, such as enfuvirtide and telaprevir. AMPs with immunomodulatory properties are currently in clinical trials. Peptides targeting yeast and bacterial infections, like pexiganan, LL-37, and PAC-113, are also under clinical evaluation.
While most Antimicrobial peptides (AMPs) have broad-spectrum activity, some are effective only against specific species or genera, making them more targeted than traditional broad-spectrum antibiotics. Resistance to many AMPs evolves at low rates and does not lead to cross-resistance with other widely used antibiotic classes.
One million prokaryotic AMP sequences were identified. 100 AMPs were synthesized and tested both in vitro and in vivo against clinically relevant drug-resistant pathogens and commensals of the human gut. Seventy-nine peptides were active, of which 63 targeted pathogens. These active AMPs exhibited antibacterial activity by disrupting bacterial membranes. Identifying the AMP sequences represents an open-access resource for antibiotic discovery.
Recent research has made great progress in finding antimicrobial peptides (AMPs) by using data from genomes and metagenomes, alongside traditional lab methods. Scientists have discovered these AMPs in various places, such as animals, humans, soil, and even from ancient human genomes, showing their promise as treatments
Antimicrobial peptides (AMPs) from the human genome and beneficial microbes are promising due to their likely low toxicity and mild antimicrobial effects, which are crucial for maintaining the balance of microbiota essential for long-term health.
The two main strategies to identify Antimicrobial peptides (AMPs) are:
Protein classification means the detection of antimicrobial peptides (AMPs) as a task of classifying protein sequences. It is effective in identifying small open reading frames (smORFs). However, it might miss AMPs that are part of larger proteins, such as cathelicidin.
Cleavage site prediction means tools like panCleave are used to predict where proteases will cleave proteins, creating fragments that could be AMPs. This method is mainly focused on human proteins. It does not directly identify AMPs in proteins or fragments from microbes.
Advancements with Protein Language Models (PLMs):
Recent developments in self-supervised PLMs, such as ESM-2 and ProtT5, have significantly advanced protein science. These models, trained on extensive datasets, are highly effective in annotating protein functions and predicting 3D structures. Due to their strong representation capabilities and structural insights, PLMs are anticipated to improve the discovery of AMPs.
Machine learning (ML) was used to predict and catalog Antimicrobial peptides (AMPs) from the global microbiome currently represented in public databases. 63,410 publicly available metagenomes and 87,920 high-quality microbial genomes were examined, revealing a wide range of AMP diversity
This resulted in 863,498 non-redundant peptide sequences comprising candidate AMPs (c_AMPs) derived from (meta)genomic data. Notably, the majority of these c_AMP sequences had not been previously described.
Antimicrobial peptides (AMP) are key players for a balanced microbiota. These peptides are part of an ancient defense system present in all organisms and have co-evolved with the complex microbiome. Notably, interactions between AMP and the microbiota are becoming increasingly significant in the gut.
Organisms produce Antimicrobial peptides (AMPs) through processes like proteolytic cleavage from an AMP-containing protein (), non-ribosomal synthesis (), or direct genome encoding ().
The host peptides can stop the bacterial formation of Bacterial Biofilm / Microbial Biofilm (BF) or disrupt its structure
Antimicrobial Peptides (AMPs) belong to an ancient defense system found in all organisms and participate in a preservative co-evolution with a complex microbiome
Mobilizing a rapid and appropriate antimicrobial response depending on the nature of each stimulus is crucial for maintaining the balance between homeostasis and inflammation in the gut
Antimicrobial Peptides are substances in the intestines that help control microbial communities, especially during times of imbalance (dysbiosis) or infection. Some bacteria produce bacterial peptides that can reduce the growth of harmful pathogens in the gut.
Antimicrobial Peptides (AMPs) are found in all areas of life
They impair cell wall integrity and cause cell lysis
Bacteria in natural habitats live in a complex balance of antagonism and mutualism. Antimicrobial peptides (AMPs) play an essential role in this. They can displace competing strains and thus facilitate cooperation.
For example, pathogens such as Shigella spp. (), Staphylococcus spp. (), Vibrio cholerae (), and Listeria spp. (; ) produce Antimicrobial peptides (AMPs) that eliminate competitors (sometimes of the same species) and allow them to occupy their niche.
Antimicrobial peptides (AMPs), short chains of 5–100 amino acids present in all organisms, offer a promising alternative with their unique microbial attack methods
A Large Number of Stimulatory Innate Immune Receptor-mediated Signals Induce Antimicrobial Peptide Expression and Secretion
Antimicrobial peptides, such as cathelicidin produced in the colon, are an important component of our innate immune system
see also:
Inflammation / Inflammatory Diseases & Neutrophils / Neutrophilic Granulocytes
Microbial products
Pathogens / Pathobionts / Pathogenic Bacteria & Probiotics (living agents)
Pyocins