Using AlphaFold Predictions in Viral Research

Current Issues in Molecular Biology, Год журнала: 2023, Номер 45(4), С. 3705 - 3732

Опубликована: Апрель 21, 2023

Elucidation of the tertiary structure proteins is an important task for biological and medical studies. AlphaFold, a modern deep-learning algorithm, enables prediction protein to high level accuracy. It has been applied in numerous studies various areas biology medicine. Viruses are entities infecting eukaryotic procaryotic organisms. They can pose danger humans economically significant animals plants, but they also be useful control, suppressing populations pests pathogens. AlphaFold used molecular mechanisms viral infection facilitate several activities, including drug design. Computational analysis bacteriophage receptor-binding contribute more efficient phage therapy. In addition, predictions discovery enzymes origin that able degrade cell wall bacterial The use assist fundamental research, evolutionary ongoing development improvement ensure its contribution study will future.

Язык: Английский

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Prediction of Klebsiella phage-host specificity at the strain level

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Май 22, 2024

Abstract Phages are increasingly considered promising alternatives to target drug-resistant bacterial pathogens. However, their often-narrow host range can make it challenging find matching phages against bacteria of interest. Current computational tools do not accurately predict interactions at the strain level in a way that is relevant and properly evaluated for practical use. We present PhageHostLearn, machine learning system predicts strain-level between receptor-binding proteins receptors Klebsiella phage-bacteria pairs. evaluate this both silico laboratory, clinically setting finding strains. PhageHostLearn reaches cross-validated ROC AUC up 81.8% maintains performance laboratory validation. Our approach provides framework developing evaluating phage-host prediction methods useful practice, which we believe be meaningful contribution machine-learning-guided development phage therapeutics diagnostics.

Язык: Английский

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Are You My Host? An Overview of Methods Used to Link Bacteriophages with Hosts

Viruses, Год журнала: 2025, Номер 17(1), С. 65 - 65

Опубликована: Янв. 5, 2025

Until recently, the only methods for finding out if a particular strain or species of bacteria could be host bacteriophage was to see infect that bacterium and kill it, releasing progeny phages. Establishing range thus meant infecting many different seeing phage each one. Detection bacterial killing can achieved on solid media (plaques, spots) broth (culture clearing). More additional link phages hosts have been developed. These include show genome entry into cells (e.g., PhageFISH); proximity genomes ligation, polonies, viral tagging); analysis metagenomes CRISPR spacer analysis, metagenomic co-occurrence). advantages disadvantages. They also are not measuring same interactions. Host divided multiple ranges, defined by how far progress in infection cycle. For example, ability effect (penetrative range) is than produce (productive range). ranges reflect defense mechanisms block growth development at various stages Here, I present comparison used identify bacteriophage-host relationships with focus what type being measured predicted.

Язык: Английский

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Viral Genome Delivery Across Bacterial Cell Surfaces

Annual Review of Microbiology, Год журнала: 2024, Номер 78(1), С. 125 - 145

Опубликована: Июль 10, 2024

In 1952, Hershey and Chase used bacteriophage T2 genome delivery inside Escherichia coli to demonstrate that DNA, not protein, is the genetic material. Over 70 years later, our understanding of structure has grown dramatically, mainly thanks cryogenic electron microscopy revolution. stark contrast, phage in prokaryotes remains poorly understood, due inherent challenge studying such a transient complex process. Here, we review current literature on viral across bacterial cell surfaces. We focus icosahedral viruses arbitrarily sort into three groups based presence size tail apparatus. inventory building blocks implicated critically analyze putative mechanisms ejection. Bacteriophage bacteria topic growing interest, given renaissance therapy Western medicine as therapeutic alternative face antibiotic resistance crisis.

Язык: Английский

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Asymmetric structure of podophage N4 from the Schitoviridae family reveals a type of tube-sheath short-tail architecture

Structure, Год журнала: 2025, Номер unknown

Опубликована: Май 1, 2025

Язык: Английский

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Asymmetric Structure of Podophage GP4 Reveals a Novel Architecture of Three Types of Tail Fibers

Journal of Molecular Biology, Год журнала: 2023, Номер 435(20), С. 168258 - 168258

Опубликована: Сен. 1, 2023

Язык: Английский

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Exploring Host-Binding Machineries of Mycobacteriophages with AlphaFold2

Journal of Virology, Год журнала: 2023, Номер 97(3)

Опубликована: Март 14, 2023

Although more than 12,000 bacteriophages infecting mycobacteria (mycobacteriophages) have been isolated so far, there is a knowledge gap on their structure-function relationships. Here, we explored the architecture of host-binding machineries from seven representative mycobacteriophages Siphoviridae family Mycobacterium smegmatis, abscessus, and tuberculosis, using AlphaFold2 (AF2). AF2 enables confident structural analyses large flexible biological assemblies resistant to experimental methods, thereby opening new avenues shed light phage structure function. Our results highlight modularity diversity siphophage that recognize host-specific receptors at onset viral infection. Interestingly, studied mycobacteriophages' present unique features compared with those phages other Gram-positive actinobacteria. they all assemble classical Dit (distal tail), Tal (tail-associated lysin), receptor-binding proteins, five them contain two potential additional adhesion proteins. Moreover, identified brush-like domains formed multiple polyglycine helices which expose hydrophobic residues as domains. These polyglycine-rich domains, observed in only native may be hallmark machineries, common nature expected. Altogether, composition indicate might evolved bind peculiar mycobacterial cell envelope, rich polysaccharides mycolic acids. This work provides rational framework efficiently produce recombinant proteins or protein test function and, hence, molecular mechanisms used by infect host. IMPORTANCE Mycobacteria include both saprophytes, such model system pathogens, tuberculosis are poorly responsive antibiotic treatments pose global public health problem. Mycobacteriophages collected very scale over last decade, proven valuable tools for genetic manipulation, rapid diagnostics, infection treatment. Yet, host remain understood. Therefore, exploring important not better understand bacteriophage-host interactions, but also rationally develop biotechnological tools. With powerful prediction software AlphaFold2, was publicly released year ago, it now possible gain functional insights challenging assemblies.

Язык: Английский

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Phage susceptibility determinants of the opportunistic pathogen Staphylococcus epidermidis

Current Opinion in Microbiology, Год журнала: 2024, Номер 78, С. 102434 - 102434

Опубликована: Фев. 16, 2024

Staphylococcus epidermidis is a common member of the human skin and nose microbiomes frequent cause invasive infections. Transducing phages accomplish horizontal transfer resistance virulence genes by mispackaging mobile-genetic elements, contributing to severe, therapy-refractory S. Lytic on other hand can be interesting candidates for new anti-S. phage therapies. Despite importance phages, we are only beginning unravel interactions. Recent studies shed light diversity, host range, receptor specificities. Modulation cell wall teichoic acids, major structures, along with defense mechanisms, crucial determinants susceptibility different groups.

Язык: Английский

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Bacteriophages from human skin infecting coagulase-negative Staphylococcus: diversity, novelty and host resistance

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Апрель 8, 2024

The human skin microbiome comprises diverse populations that differ temporally between body sites and individuals. virome is a less studied component of the study bacteriophages required to increase knowledge modulation stability bacterial communities. Staphylococcus species are among most abundant colonisers associated with both health disease yet infecting on well studied. Here, we report isolation genome sequencing 40 from swabs infect coagulase-negative (CoNS) species, which extends our phage diversity. Six genetic clusters phages were identified two representing novel phages, one characterise name Alsa phage. We have greater ability S. hominis was otherwise infected than other CoNS by isolated indicating an undescribed barrier infection could be in part due numerous restriction-modification systems. extended diversity here enables further research define their contribution mechanisms limit infection.

Язык: Английский

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Structure of the Portal Complex from Staphylococcus aureus Pathogenicity Island 1 Transducing Particles In Situ and In Isolation

Journal of Molecular Biology, Год журнала: 2023, Номер 436(4), С. 168415 - 168415

Опубликована: Дек. 21, 2023

Язык: Английский

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