Discovery of Antimicrobial Lysins from the “Dark Matter” of Uncharacterized Phages Using Artificial Intelligence

Advanced Science, Journal Year: 2024, Volume and Issue: 11(32)

Published: June 20, 2024

Abstract The rapid rise of antibiotic resistance and slow discovery new antibiotics have threatened global health. While novel phage lysins emerged as potential antibacterial agents, experimental screening methods for pose significant challenges due to the enormous workload. Here, first unified software package, namely DeepLysin, is developed employ artificial intelligence mining vast genome reservoirs (“dark matter”) lysins. Putative are computationally screened from uncharacterized Staphylococcus aureus phages 17 randomly selected validation. Seven candidates exhibit excellent in vitro activity, with LLysSA9 exceeding that best‐in‐class alternative. efficacy further demonstrated mouse bloodstream wound infection models. Therefore, this study demonstrates integrating computational approaches expedite proteins combating increasing antimicrobial resistance.

Language: Английский

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Exploration of the feasibility of clinical application of phage treatment for multidrug-resistant Serratia marcescens -induced pulmonary infection

Emerging Microbes & Infections, Journal Year: 2025, Volume and Issue: 14(1)

Published: Jan. 7, 2025

Serratia marcescens (S. marcescens) commonly induces refractory infection due to its multidrug-resistant nature. To date, there have been no reports on the application of phage treatment for S. infection. This study was conducted explore feasibility in treating by collaborating with a 59-year-old male patient pulmonary marcescens. Our experiments included three domains: i) selection appropriate phage, ii) verification efficacy and safety selected iii) confirmation phage-bacteria interactions. results showed that Spe5P4 is Treatment good efficacy, manifested as amelioration symptoms, hydrothorax examinations, chest computed tomography findings. Phage did not worsen hepatic renal function, immunity-related indices, or indices routine blood examination. It induce deteriorate drug resistance involved antibiotics. Importantly, adverse events were reported during follow-up periods. Thus, satisfactory safety. Finally, we found increase bacterial load, cytotoxicity, virulence, marcescens, indicating interactions between which are useful future against work provides evidence working basis further infections. We also provided methodological investigating clinical infections future.

Language: Английский

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deep-AMPpred: A Deep Learning Method for Identifying Antimicrobial Peptides and Their Functional Activities

Journal of Chemical Information and Modeling, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 10, 2025

Antimicrobial peptides (AMPs) are small that play an important role in disease defense. As the problem of pathogen resistance caused by misuse antibiotics intensifies, identification AMPs as alternatives to has become a hot topic. Accurately identifying using computational methods been key issue field bioinformatics recent years. Although there many machine learning-based AMP tools, most them do not focus on or only few functional activities. Predicting multiple activities antimicrobial can help discover candidate with broad-spectrum ability. We propose two-stage predictor deep-AMPpred, which first stage distinguishes from other peptides, and second solves multilabel 13 common AMP. deep-AMPpred combines ESM-2 model encode features integrates CNN, BiLSTM, CBAM models its The captures global contextual peptide sequence, while combine local feature extraction, long-term short-term dependency modeling, attention mechanisms improve performance function prediction. Experimental results demonstrate performs well accurately predicting their This confirms effectiveness capture meaningful sequence integrating deep learning for activity

Language: Английский

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Efficacy of Phage Application in Modulating Raw Milk Microbiota: Targeting Escherichia coli, Pseudomonas fluorescens, and Lactiplantibacillus plantarum

Food Control, Journal Year: 2025, Volume and Issue: unknown, P. 111166 - 111166

Published: Jan. 1, 2025

Language: Английский

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Electrochemiluminescence Resonance Energy Transfer Biosensor for the Human-Associated Clade of Streptococcus suis Based on Prereduction-Enhanced Yttrium MOFs

Analytical Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 21, 2025

Streptococcus suis, a significant zoonotic pathogen, annually caused substantial economic losses in the swine industry and had intensified threat to public health due recent emergence of human-associated clade. In this study, we discovered that rare-earth metal-based metal-organic frameworks (Y-BTC) possessed excellent ECL capabilities. After prereduction at high voltage, its intensity was enhanced by two times. Subsequently, developed an efficient CRISPR/Cas12a-mediated electrochemiluminescence resonance energy transfer (ECL-RET) biosensor utilizing Y-BTC for detection S. suis employed as ECL-RET donor emitter, spherical nucleic acid Au NP utilized receptor. presence target, isothermal amplification triggered generate large number amplicons, which subsequently activated trans-cleavage activity Cas12a. Cas12a cleaved shell on surface NPs, reducing spatial distance between NPs electrostatic adsorption, thereby quenching via ECL-RET. Consequently, targets can be observed reduced signal. The sensor exhibited range 25 pM 50 nM, with limit low 17 pM. practical utility verified through actual sample testing. Our proposed sensing strategy provides new avenue sensitive suis. universality has also been demonstrated using Fusobacterium nucleatum, Salmonella pullorum, Listeria monocytogenes, holding great promise field food safety health.

Language: Английский

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Prevalence of Zoonotic Diseases in the Northeastern region, One Health perspective

Animals and zoonoses., Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Phage engineering using synthetic biology and artificial intelligence to enhance phage applications in food industry

Current Opinion in Food Science, Journal Year: 2025, Volume and Issue: unknown, P. 101274 - 101274

Published: Jan. 1, 2025

Language: Английский

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Phage‐Based Biocontrol Strategies and Application in Aquatic Animal Disease Prevention and Control

Reviews in Aquaculture, Journal Year: 2025, Volume and Issue: 17(3)

Published: April 7, 2025

ABSTRACT Aquaculture is essential for meeting future demands food, yet it faces significant losses from infectious bacterial diseases. has recently been critically imperiled by the emergence of multi‐drug‐resistant bacteria, as relies significantly on use antibiotics prevention and treatment. The multidrug‐resistant bacteria poses a critical threat to aquaculture, which heavily Bacteriophage (phage) therapy regained attention with spread drug‐resistant bacteria. Phages are viruses that specifically infect archaea. As promising therapeutic strategy aquatic diseases, phage offers strong specificity, low resistance potential, rapid metabolism, ease development, cost‐effectiveness. In this review, we discuss advantages, opportunities, challenges therapy, summarizing status research highlighting emerging technologies aimed at enhancing in aquaculture. Finally, review looks future, identifying scientific technological advances necessary establish viable universal alternative

Language: Английский

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Harnessing advanced computational approaches to design novel antimicrobial peptides against intracellular bacterial infections

Bioactive Materials, Journal Year: 2025, Volume and Issue: 50, P. 510 - 524

Published: April 28, 2025

Language: Английский

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Discovery of a novel antimicrobial protein from Lactobacillus plantarum by computational screening and experimental evaluation

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: 311, P. 143920 - 143920

Published: May 9, 2025

Language: Английский

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