MuLAN: Mutation-driven Light Attention Networks for investigating protein-protein interactions from sequences | Brvbi | RMH (2024)

Table of Contents
Nitrite reductase–mimicking catalysis temporally regulating nitric oxide concentration gradient adaptive for antibacterial therapy | SAdv Greenhouse gas emissions in US beef production can be reduced by up to 30% with the adoption of selected mitigation measures | Nfd Tail assembly interference is a common strategy in bacterial antiviral defenses | Ncm Unraveling the role of urea hydrolysis in salt stress response during seed germination and seedling growth in Arabidopsis thaliana Metagenomic analyses of the plastisphere reveals a common functional potential across oceans | Brvbi Recent advances in the biosynthetic studies of bacterial organoarsenic natural products - Npr Construction nanobiotechnology approach for performance enhancement of microbially induced biomineralization (MIB) using a biopolymer encapsulated spore-based system | AEM Enhanced Salt Tolerance in Synechocystis sp. PCC 6803 Through Adaptive Evolution: Mechanisms and Applications for Environmental Bioremediation | Brve Genomically recoded Escherichia coli with optimized functional phenotypes | Brvsb Cyanobacterial biofilms: from natural systems to applications | TiB Hijackers, hitchhikers, or co-drivers? The mysteries of mobilizable genetic elements | PLOS Cell-free synthesis of infective phages from in vitro assembled phage genomes for efficient phage engineering and production of large phage libraries | Sbio Host-associated microbes mitigate the negative impacts of aquatic pollution | mSys Elucidating human gut microbiota interactions that robustly inhibit diverse Clostridioides difficile strains across different nutrient landscapes | Ncm A Foundation Model Identifies Broad-Spectrum Antimicrobial Peptides against Drug-Resistant Bacterial Infection | Ncm Giant viruses as reservoirs of antibiotic resistance genes | Ncm From Static to Dynamic Structures: Improving Binding Affinity Prediction with Graph-Based Deep Learning | AdvS Efficient genome-editing tools to engineer the recalcitrant non-model industrial microorganism Zymomonas mobilis | TiB microRNA maintains nutrient homeostasis in the symbiont–host interaction | pnas Experimental capture of genomic islands defines a widespread class of genetic element capable of non-autonomous transfer | Brveco Co-zorbs: Motile, multispecies biofilms aid transport of diverse bacterial species | Brveco Bacillus lipopeptides as key players in rhizosphere chemical ecology | TiM CRISPR/dCas-mediated counter-silencing: Reprogramming dCas proteins into antagonists of xenogeneic silencers | Brvbe Biotechnological advances in the production of unusual fatty acids in transgenic plants and recombinant microorganisms | BAdv Bacterial cell surface characterization by phage display coupled to high-throughput sequencing | Ncm References

MuLAN: Mutation-driven Light Attention Networks for investigating protein-protein interactions from sequences | Brvbi | RMH (1)Your new post is loading...

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August 30, 2:35 PM

MuLAN: Mutation-driven Light Attention Networks for investigating protein-protein interactions from sequences | Brvbi | RMH (3)Scoop.it!

From www.science.org - August 30, 2:34 PM

The unique bacterial infection microenvironment (IME) usually requires complicated design of nanomaterials to adapt to IME for enhancing antibacterial therapy. Here, an alternative IME adaptative nitrite reductase–mimicking nanozyme is constructed by in situ growth of ultrasmall copper sulfide clusters on the surface of a nanofibrillar lysozyme assembly (NFLA/CuS NHs), which can temporally regulate nitric oxide (NO) gradient concentration to kill bacteria initially and promote tissue regeneration subsequently. Benefiting from a copper nitrite reductase (CuNIR)–inspired structure with CuS cluster as active center and NFLA as skeleton, NFLA/CuS NHs efficiently boost the catalytic reduction of nitrite to NO. The inherent supramolecular fibrillar networks displays excellent bacterial capture capability, facilitating initial high-concentration NO attacks on the bacteria. The subsequent catalytic release of low-concentration NO by NFLA/CuS NHs–mediated nitrite reduction remarkably promotes cell migration and angiogenesis. This work paves the way for dynamically eliminating MDR bacterial infection and promoting tissue regeneration in a simple and smart way through CuNIR-mimicking catalysis.

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August 30, 1:39 PM

MuLAN: Mutation-driven Light Attention Networks for investigating protein-protein interactions from sequences | Brvbi | RMH (7)Scoop.it!

From www.nature.com - August 29, 5:00 PM

Greenhouse gas (GHG) emissions from beef production in the United States are unevenly distributed across the supply chain and production regions, complicating where and how to reduce emissions most effectively. Using spatially explicit life cycle assessment methods, we quantify the baseline GHG emissions and mitigation opportunities of 42 practices spanning the supply chain from crop and livestock production to processing. We find that the potential to reduce GHGs across the beef sector ranges up to 30% (20 million tonnes CO2e reduced and 58 million tonnes CO2 sequestered each year relative to the baseline) under ubiquitous adoption assumptions, largely driven by opportunities in the grazing stage. Opportunities to reduce GHGs in the feed, grazing and feedlot stages vary across regions, yet large-scale adoption across the entire beef supply chain is important. These findings reveal promising locations and practices to invest in to advance mitigation goals and an upper-end theoretical potential for mitigation in the beef industry. The United States is the world’s largest beef producer. Identifying strategies to mitigate its GHG emissions remains a challenge due to sector complexity and heterogeneity. This study takes an LCA approach to quantify potential mitigation opportunities available or soon to be available for the beef sector.

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August 30, 12:52 PM

MuLAN: Mutation-driven Light Attention Networks for investigating protein-protein interactions from sequences | Brvbi | RMH (11)Scoop.it!

From www.nature.com - August 29, 5:00 PM

Many bacterial immune systems recognize phage structural components to activate antiviral responses, without inhibiting the function of the phage component. These systems can be encoded in specific chromosomal loci, known as defense islands, and in mobile genetic elements such as prophages and phage-inducible chromosomal islands (PICIs). Here, we identify a family of bacterial immune systems, named Tai (for ‘tail assembly inhibition’), that is prevalent in PICIs, prophages and P4-like phage satellites. Tai systems protect their bacterial host population from other phages by blocking the tail assembly step, leading to the release of tailless phages incapable of infecting new hosts. To prevent autoimmunity, some Tai-positive phages have an associated counter-defense mechanism that is expressed during the phage lytic cycle and allows for tail formation. Interestingly, the Tai defense and counter-defense genes are organized in a non-contiguous operon, enabling their coordinated expression. Bacterial immune systems can recognize phage structural components to activate diverse antiviral responses. Here, the authors identify a family of bacterial immune systems, encoded in prophages and other mobile genetic elements, that protect their bacterial host population from other invading phages by blocking tail assembly.

?'s insight:

antiphage, all the evolved phages uniquely presented one or two amino acid substitutions (depending on the phage) in the tail proteins. Since the tip attachment protein J plays crucial roles in both recognizing the receptor in the mature particle and initiating the tail phage formation49, we hypothesized that the Tai proteins could act either as superinfection exclusion systems or blocking tail formation.

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August 30, 12:04 PM

MuLAN: Mutation-driven Light Attention Networks for investigating protein-protein interactions from sequences | Brvbi | RMH (15)Scoop.it!

From elifesciences.org - July 21, 5:00 PM

Urea is intensively utilized as a nitrogen fertilizer in agriculture, originating either from root uptake or from catabolism of arginine by arginase. Despite its extensive use, the underlying physiological mechanisms of urea, particularly its adverse effects on seed germination and seedling growth under salt stress, remain unclear. In this study, we demonstrate that salt stress induces excessive hydrolysis of arginine-derived urea, leading to an increase in cytoplasmic pH within seed radical cells, which, in turn, triggers salt-induced inhibition of seed germination (SISG) and hampers seedling growth. Our findings challenge the long-held belief that ammonium accumulation and toxicity are the primary causes of SISG, offering a novel perspective on the mechanism underlying these processes. This study provides significant insights into the physiological impact of urea hydrolysis under salt stress, contributing to a better understanding of SISG.

?'s insight:

https://elifesciences.org/articles/101732 (A) In non-saline soil conditions (top), seeds (brown circles) germinate and grow to become seedlings (green). In saline soil (bottom), which contains more sodium (Na+; pink) and chlorine (Cl-; blue) ions, seed germination is inhibited. (B) Under salt stress conditions, protein degradation in the seed creates arginine, which is converted to urea by arginase. The urea is subsequently hydrolyzed by urease, resulting in increased levels of ammonium ions (NH4+), bicarbonate ions (HCO3-), and hydroxide ions (OH-). The bicarbonate ions and hydroxide ions increase the cytoplasmic pH (pHcyt), thereby inhibiting seed germination.

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August 30, 9:19 AM

MuLAN: Mutation-driven Light Attention Networks for investigating protein-protein interactions from sequences | Brvbi | RMH (19)Scoop.it!

From www.biorxiv.org - August 28, 5:00 PM

Trillions of plastic particles have accumulated in the oceans, covered by microbial biofilms (termed the 'plastisphere') whose functional potential remains unexplored. We evaluated genome-resolved bacterial metagenomes of the plastisphere from the North Atlantic and North Pacific garbage patches and compared their structure and functional potential to ambient plankton. Our data revealed a characteristic genetic potential of the plastisphere with functionally equivalent taxonomic units across both oceans. We found fewer coding genes, smaller genome sizes and lower GC-content in plankton in comparison to the plastisphere, despite residing in the same environment, reflecting a greater nutrient demand in the plastisphere. A functional gene analysis confirmed that the plastisphere consists of microorganisms with a higher potential to control their nutrient supply, metabolize a wider range of carbon sources, attenuate free radicals and use alternative energy sources like anoxygenic photosynthesis. Our results suggest that the overriding factor for the high functional similarity of the plastisphere in both oceans is the habitat for biofilm formation with the potential to support mutualism and nutrient sharing making genomic streamlining as found in plankton, unnecessary. Consequently, increasing plastic pollution promotes the expansion of new functional units within oligotrophic oceans, with the potential to impact biogeochemical cycles.

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August 29, 11:24 PM

MuLAN: Mutation-driven Light Attention Networks for investigating protein-protein interactions from sequences | Brvbi | RMH (23)Scoop.it!

From pubs.rsc.org - August 29, 11:24 PM

Arsenic is widely distributed throughout terrestrial and aquatic environments, mainly in highly toxic inorganic forms. To adapt to environmental inorganic arsenic, bacteria have evolved ubiquitous arsenic metabolic strategies by combining arsenite methylation and related redox reactions, which have been extensively studied. Recent reports have shown that some bacteria have specific metabolic pathways associated with structurally and biologically unique organoarsenic natural products. In this highlight, by exemplifying the cases of oxo-arsenosugars, arsinothricin, and bisenarsan, we summarize recent advances in the identification and biosynthesis of bacterial organoarsenic natural products. We also discuss the potential discoveries of novel arsenic-containing natural products of bacterial origins.

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August 29, 10:55 PM

MuLAN: Mutation-driven Light Attention Networks for investigating protein-protein interactions from sequences | Brvbi | RMH (27)Scoop.it!

From journals.asm.org - August 29, 10:55 PM

The integration of green construction practices within the built environment has been significantly advanced by biotechnological innovations, among which microbially induced biomineralization (MIB), predominantly facilitated by various strains of spore-forming bacilli, emerges as a pivotal mechanism for the self-healing of concrete. However, the practical deployment of this technology faces challenges, notably the compromised viability of bacterial spores due to germination triggered by severe shear stress during concrete mixing. To address this limitation, a water-insoluble polymer (extracellular polymeric substance) produced byCellulomonas flavigenawas utilized to encapsulate and protect the spores. The encapsulation process was rigorously verified through physicochemical methodologies, including X-ray diffraction (XRD) analysis, which revealed alterations in the interlayer spacings of the extracellular polymeric substance (EPS) structure during the encapsulation process, indicating successful EPS coating of the spores. Furthermore, a proof of concept for the enhanced biomineralization capacity of EPS-coated spores was demonstrated. Standard analytical techniques confirmed the precipitation of calcite and vaterite among other minerals, underscoring the effectiveness of this novel approach. This breakthrough paves the way for the development of innovative, sustainable bioconcrete applications, aligning with broader environmental objectives and advancing the field of green construction technology.

?'s insight:

hydrogel, encapsulating Paenibacillus alkalitererraea (PA) spores to enhance their performance in biomineralization. The encapsulating material was a hydrophobic extracellular polymeric substance (EPS) that was extracted from the cells of a cellulolytic bacterium, Cellulomonas flavigena.

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August 29, 10:26 PM

MuLAN: Mutation-driven Light Attention Networks for investigating protein-protein interactions from sequences | Brvbi | RMH (31)Scoop.it!

From www.biorxiv.org - August 28, 5:00 PM

Salt stress is common in natural environments, where elevated salt levels in brackish water and saline soil can hinder the growth of organisms, thereby exacerbating environmental challenges. Developing salt-tolerant organisms not only uncovers novel mechanisms of salt tolerance but also lays the groundwork for managing and utilizing saline environments. Cyanobacteria, which are widely distributed in hydrosphere and soil, serve as ideal models for studying salt stress. In this study, the model cyanobacterium Synechocystis sp. PCC 6803 was selected, whose salt (NaCl) tolerance improved from 4.0% to 6.5% (m/v) through adaptive laboratory evolution. Genome re-sequencing and mutant analysis identified six key genes associated with salt tolerance. Notably, the deletion of slr1670, which encodes glycerol glucoside hydrolase, improved the strain's salt tolerance. In addition, slr1753 encodes a membrane protein that may enhance salt tolerance by facilitating ion transport to the extracellular space. Further analysis revealed that overexpression of slr1753 significantly accumulates Na+ on the cell surface, enabling effective seawater treatment using the engineered strain, resulting in a 6.35% reduction of Na+ in the seawater. Moreover, the adapted bacteria can be used for the remediation of saline soil samples, leading to a 184.2% and 43.8% increase in the germination rate and average height of Brassica rapa chinensis, respectively, along with a 25.3% rise in total organic carbon content and reductions in both total salt content by 1.82% and pH by 1.91% in soil. This study provides novel insights into salt tolerance mechanisms and the bioremediation of high-salinity environments.

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ale salt

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August 29, 10:16 PM

MuLAN: Mutation-driven Light Attention Networks for investigating protein-protein interactions from sequences | Brvbi | RMH (34)Scoop.it!

From www.biorxiv.org - August 28, 5:00 PM

Genomically recoded organisms hold promise for many biotechnological applications, but they may exhibit substantial fitness defects relative to their non-recoded counterparts. We used targeted metabolic screens, genetic analysis, and proteomics to identify the origins of fitness impairment in a model recoded organism, Escherichia coli C321.∆A. We found that defects in isoleucine biosynthesis and release factor activity, caused by mutations extant in all K-12 lineage strains, elicited profound fitness impairments in C321.∆A, suggesting that genome recoding exacerbates suboptimal traits present in precursor strains. By correcting these and other C321.∆A-specific mutations, we engineered C321.∆A strains with doubling time reductions of 17% and 42% in rich and minimal medium, respectively, compared to ancestral C321. Strains with improved growth kinetics also demonstrated enhanced ribosomal non-standard amino acid incorporation capabilities. Proteomic analysis indicated that C321.∆A lacks the ability to regulate essential amino acid and nucleotide biosynthesis pathways, and that targeted mutation reversion restored regulatory capabilities. Our work outlines a strategy for the rapid and precise phenotypic optimization of genomically recoded organisms and other engineered microbes.

?'s insight:

Pearl Bio, industry, isaacs f, 2st, in minimal medium supplemented with combinations of amino acids, nucleotides, essential cofactors, and trace minerals, we identified metabolites whose omission reduces C321 growth. We found a deficiency in isoleucine biosynthesis.

We performed Gene Ontology (GO) enrichment analysis on significant gene sets using the PANTHER classification system (www.pantherdb.org) using the E. coli all-gene reference list and the GO biological process annotation list.

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August 29, 9:21 PM

MuLAN: Mutation-driven Light Attention Networks for investigating protein-protein interactions from sequences | Brvbi | RMH (38)Scoop.it!

From www.cell.com - August 29, 9:21 PM

Cyanobacteria are the ancestors of oxygenic photosynthesis. Fueled by light and water, their ability to reduce CO2 to sugar holds potential for carbon-neutral production processes. Due to challenges connected to cultivation and engineering issues, cyanobiotechnology has yet to be able to establish itself broadly in industry. In recent years, applying cyanobacterial biofilms as whole-cell biocatalysts instead of suspension cultures has emerged as a novel concept to counteract low cell densities and low reaction stability, critical challenges in cyanobacterial applications. This review explores the potential of cyanobacterial biofilms for biotechnology and bioremediation. It briefly introduces cyanobacteria as primary producers in natural structured microbial communities; describes various applications in biotechnology and bioremediation; and discusses innovations, challenges, and future trends in this exciting research field.

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August 29, 9:10 PM

MuLAN: Mutation-driven Light Attention Networks for investigating protein-protein interactions from sequences | Brvbi | RMH (42)Scoop.it!

From journals.plos.org - August 29, 9:10 PM

Mobile genetic elements shape microbial gene repertoires and populations. Recent results reveal that many, possibly most, microbial mobile genetic elements require helpers to transfer between genomes, which we refer to as Hitcher Genetic Elements (hitchers or HGEs). They may be a large fraction of pathogenicity and resistance genomic islands, whose mechanisms of transfer have remained enigmatic for decades. Together with their helper elements and their bacterial hosts, hitchers form tripartite networks of interactions that evolve rapidly within a parasitism–mutualism continuum. In this emerging view of microbial genomes as communities of mobile genetic elements many questions arise. Which elements are being moved, by whom, and how? How often are hitchers costly hyper-parasites or beneficial mutualists? What is the evolutionary origin of hitchers? Are there key advantages associated with hitchers’ lifestyle that justify their unexpected abundance? And why are hitchers systematically smaller than their helpers? In this essay, we start answering these questions and point ways ahead for understanding the principles, origin, mechanisms, and impact of hitchers in bacterial ecology and evolution.

?'s insight:

1str, rocha epc

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August 29, 8:39 PM

MuLAN: Mutation-driven Light Attention Networks for investigating protein-protein interactions from sequences | Brvbi | RMH (46)Scoop.it!

From academic.oup.com - August 23, 5:00 PM

Bacteriophages are promising alternatives to traditional antimicrobial treatment of bacterial infections. To further increase the potential of phages, efficient engineering methods are needed. This study investigates an approach to phage engineering based on phage rebooting and compares selected methods of assembly and rebooting of phage genomes. Golden Gate assembly of phage genomes and subsequent rebooting by cell-free transcription-translation reactions yielded the most efficient phage engineering and allowed production of a proof-of-concept T7 phage library of 1.8.107phages. We obtained 7.5.106 different phages, demonstrating generation of large and diverse libraries suitable for high-throughput screening of mutant phenotypes. Implementing versatile and high-throughput phage engineering methods allows vastly accelerated and improved phage engineering, bringing us closer to applying effective phages to treat infections in the clinic.

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August 29, 2:58 PM

MuLAN: Mutation-driven Light Attention Networks for investigating protein-protein interactions from sequences | Brvbi | RMH (50)Scoop.it!

From journals.asm.org - August 29, 2:58 PM

Pollution can negatively impact aquatic ecosystems, aquaculture operations, and recreational water quality. Many aquatic microbes can sequester or degrade pollutants and have been utilized for bioremediation. While planktonic and benthic microbes are well-studied, host-associated microbes likely play an important role in mitigating the negative impacts of aquatic pollution and represent an unrealized source of microbial potential. For example, aquatic organisms that thrive in highly polluted environments or concentrate pollutants may have microbiomes adapted to these selective pressures. Understanding microbe–pollutant interactions in sensitive and valuable species could help protect human well-being and improve ecosystem resilience. Investigating these interactions using appropriate experimental systems and overcoming methodological challenges will present novel opportunities to protect and improve aquatic systems. In this perspective, we review examples of how microbes could mitigate negative impacts of aquatic pollution, outline target study systems, discuss challenges of advancing this field, and outline implications in the face of global changes.

?'s insight:

beneficial functions is host-associated microbes that degrade oil or toxic oil constituents, including polycyclic aromatic hydrocarbons (PAHs). Excess nutrients (particularly nitrogen and phosphorus) frequently enter aquatic systems from agricultural and urban activities. Nutrient over-enrichment can cause excess algal growth, which can impair water quality, reduce oxygen, and cause acute toxicity. . Extensive research explores how plastics impact aquatic host and environmental microbiomes.

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August 30, 1:59 PM

MuLAN: Mutation-driven Light Attention Networks for investigating protein-protein interactions from sequences | Brvbi | RMH (54)Scoop.it!

From www.nature.com - August 27, 5:00 PM

The human gut pathogen Clostridioides difficile displays substantial inter-strain genetic variability and confronts a changeable nutrient landscape in the gut. We examined how human gut microbiota inter-species interactions influence the growth and toxin production of various C. difficile strains across different nutrient environments. Negative interactions influencing C. difficile growth are prevalent in an environment containing a single highly accessible resource and sparse in an environment containing C. difficile-preferred carbohydrates. C. difficile toxin production displays significant community-context dependent variation and does not trend with growth-mediated inter-species interactions. C. difficile strains exhibit differences in interactions with Clostridium scindens and the ability to compete for proline. Further, C. difficile shows substantial differences in transcriptional profiles in co-culture with C. scindens or Clostridium hiranonis. C. difficile exhibits massive alterations in metabolism and other cellular processes in co-culture with C. hiranonis, reflecting their similar metabolic niches. C. hiranonis uniquely inhibits the growth and toxin production of diverse C. difficile strains across different nutrient environments and robustly ameliorates disease severity in mice. In sum, understanding the impact of C. difficile strain variability and nutrient environments on inter-species interactions could help improve the effectiveness of anti-C. difficile strategies. In this paper, the authors usea systems biology approach toexplore human gut microbiota interactions impacting multiple Clostridioides difficile strains in various nutrient environments, showing that Clostridium hiranonis robustly inhibits C. difficile, reducing disease severity in mice.

?'s insight:

Venturelli, 1str, metabolic niche overlap to inhibit difficile. the large variation in toxin production ofC. difficilein communities was not correlated with growth-mediated inter-species interactions. Our workflow identifiesClostridium hiranonisas a “universal”C. difficile growth and toxin production inhibitor due toits high metabolic niche overlap withC. difficile, which in turn could block the utilization ofC. difficile-preferred substrates.

The identity of bacterial species was verified using the GTDB toolkit 2.1.0103using the database version 207. All assemblies were classified asClostridioides difficile by average nucleotide identity and placement in the GTDB reference tree.De novo gene predictions of the assemblies were performed by Prodigal 2.6.3104. Metabolic draft models were built using CarveMe 1.5.2105from the isolate gene predictions using DIAMOND 2.1.6106with additional options of “--more-sensitive –top 10”

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August 30, 1:28 PM

MuLAN: Mutation-driven Light Attention Networks for investigating protein-protein interactions from sequences | Brvbi | RMH (58)Scoop.it!

From www.nature.com - August 29, 5:00 PM

Development of potent and broad-spectrum antimicrobial peptides (AMPs) could help overcome the antimicrobial resistance crisis. We develop a peptide language-based deep generative framework (deepAMP) for identifying potent, broad-spectrum AMPs. Using deepAMP to reduce antimicrobial resistance and enhance the membrane-disrupting abilities of AMPs, we identify, synthesize, and experimentally test 18 T1-AMP (Tier 1) and 11 T2-AMP (Tier 2) candidates in a two-round design and by employing cross-optimization-validation. More than 90% of the designed AMPs show a better inhibition than penetratin in both Gram-positive (i.e., S. aureus) and Gram-negative bacteria (i.e., K. pneumoniae and P. aeruginosa). T2-9 shows the strongest antibacterial activity, comparable to FDA-approved antibiotics. We show that three AMPs (T1-2, T1-5 and T2-10) significantly reduce resistance to S. aureus compared to ciprofloxacin and are effective against skin wound infection in a female wound mouse model infected with P. aeruginosa. In summary, deepAMP expedites discovery of effective, broad-spectrum AMPs against drug-resistant bacteria. New approaches to develop antimicrobial agents are urgently needed. In this study, the authors develop a peptide language-based deep generative model to design broad-spectrum antimicrobial peptides against drug-resistant bacteria and validate promising candidates in a wound mouse model.

?'s insight:

we constructed Amps Training Pairs and Penetratin Training Pairs datasets (cf. Methods) by a degenerative workflow, and feed these to finetune the pretrained model. The deepAMP-POM was used to optimize penetratin model, and thebdeepAMP-predict were used to rank these candidates

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August 30, 12:39 PM

MuLAN: Mutation-driven Light Attention Networks for investigating protein-protein interactions from sequences | Brvbi | RMH (62)Scoop.it!

From www.nature.com - August 29, 5:00 PM

Nucleocytoplasmic large DNA viruses (NCLDVs; also called giant viruses), constituting the phylum Nucleocytoviricota, can infect a wide range of eukaryotes and exchange genetic material with not only their hosts but also prokaryotes and phages. A few NCLDVs were reported to encode genes conferring resistance to beta‑lactam, trimethoprim, or pyrimethamine, suggesting that they are potential vehicles for the transmission of antibiotic resistance genes (ARGs) in the biome. However, the incidence of ARGs across the phylum Nucleocytoviricota, their evolutionary characteristics, their dissemination potential, and their association with virulence factors remain unexplored. Here, we systematically investigated ARGs of 1416 NCLDV genomes including those of almost all currently available cultured isolates and high-quality metagenome-assembled genomes from diverse habitats across the globe. We reveal that 39.5% of them carry ARGs, which is approximately 37 times higher than that for phage genomes. A total of 12 ARG types are encoded by NCLDVs. Phylogenies of the three most abundant NCLDV-encoded ARGs hint that NCLDVs acquire ARGs from not only eukaryotes but also prokaryotes and phages. Two NCLDV-encoded trimethoprim resistance genes are demonstrated to confer trimethoprim resistance in Escherichia coli. The presence of ARGs in NCLDV genomes is significantly correlated with mobile genetic elements and virulence factors. Nucleocytoplasmic large DNA viruses, or ‘giant viruses’, infect a wide range of eukaryotes and can exchange genetic material not only with their hosts but also with bacteria and phages. Here, the authors show that many giant viruses carry diverse antibiotic resistance genes, which are associated with mobile genetic elements and genes encoding potential virulence factors.

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August 30, 12:01 PM

MuLAN: Mutation-driven Light Attention Networks for investigating protein-protein interactions from sequences | Brvbi | RMH (66)Scoop.it!

From onlinelibrary.wiley.com - August 30, 12:01 PM

Accurate prediction of protein-ligand binding affinities is an essential challenge in structure-based drug design. Despite recent advances in data-driven methods for affinity prediction, their accuracy is still limited, partially because they only take advantage of static crystal structures while the actual binding affinities are generally determined by the thermodynamic ensembles between proteins and ligands. One effective way to approximate such a thermodynamic ensemble is to use molecular dynamics (MD) simulation. Here, an MD dataset containing 3,218 different protein-ligand complexes is curated, and Dynaformer, a graph-based deep learning model is further developed to predict the binding affinities by learning the geometric characteristics of the protein-ligand interactions from the MD trajectories. In silico experiments demonstrated that the model exhibits state-of-the-art scoring and ranking power on the CASF-2016 benchmark dataset, outperforming the methods hitherto reported. Moreover, in a virtual screening on heat shock protein 90 (HSP90) using Dynaformer, 20 candidates are identified and their binding affinities are further experimentally validated. Dynaformer displayed promising results in virtual drug screening, revealing 12 hit compounds (two are in the submicromolar range), including several novel scaffolds. Overall, these results demonstrated that the approach offer a promising avenue for accelerating the early drug discovery process.

?'s insight:

docking

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August 29, 11:27 PM

MuLAN: Mutation-driven Light Attention Networks for investigating protein-protein interactions from sequences | Brvbi | RMH (70)Scoop.it!

From www.cell.com - August 29, 11:27 PM

Current biotechnology relies on a few well-studied model organisms, such asEscherichia coliandSaccharomyces cerevisiae, for which abundant information and efficient toolkits are available for genetic manipulation, but which lack industrially favorable characteristics. Non-model industrial microorganisms usually do not have effective and/or efficient genome-engineering toolkits, which hampers the development of microbial cell factories to meet the fast-growing bioeconomy. In this study, using the non-model ethanologenic bacteriumZymomonas mobilisas an example, we developed a workflow to mine and temper the elements of restriction–modification (R-M), CRISPR/Cas, toxin–antitoxin (T-A) systems, and native plasmids, which are hidden within industrial microorganisms themselves, as efficient genome-editing toolkits, and established a genome-wide iterative and continuous editing (GW-ICE) system for continuous genome editing with high efficiency. This research not only provides tools and pipelines for engineering the non-model polyploid industrial microorganismZ. mobilisefficiently, but also sets a paradigm to overcome biotechnological limitations in other genetically recalcitrant non-model industrial microorganisms.

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genome edition

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August 29, 11:05 PM

MuLAN: Mutation-driven Light Attention Networks for investigating protein-protein interactions from sequences | Brvbi | RMH (74)Scoop.it!

From www.pnas.org - August 29, 11:05 PM

Endosymbionts provide essential nutrients for hosts, promoting growth, development, and reproduction. However, the molecular regulation of nutrient transport from endosymbiont to host is not well understood. Here, we used bioinformatic analysis, RNA-seq, luciferase assays, RNA immunoprecipitation, and in situ hybridization to show that a bacteriocyte-distributed MRP4 gene (multidrug resistance-associated protein 4) is negatively regulated by a host (aphid)-specific microRNA (miR-3024). Targeted metabolomics, microbiome analysis, vitamin B6 (VB6) supplements, 3D modeling/molecular docking, in vitro binding assays (voltage clamp recording and microscale thermophoresis), and functional complementation of Escherichia coliwere jointly used to show that the miR-3024/MRP4 axis controls endosymbiont (Serratia)-produced VB6 transport to the host. The supplementation of miR-3024 increased the mortality of aphids, but partial rescue was achieved by providing an external source of VB6. The use of miR-3024 as part of a sustainable aphid pest-control strategy was evaluated by safety assessments in nontarget organisms (pollinators, predators, and entomopathogenic fungi) using virus-induced gene silencing assays and the expression of miR-3024 in transgenic tobacco. The supplementation of miR-3024 suppresses MRP4expression, restricting the number of membrane channels, inhibiting VB6 transport, and ultimately killing the host. Under aphids facing stress conditions, the endosymbiont titer is decreased, and the VB6 production is also down-regulated, while the aphid’s autonomous inhibition of miR-3024 enhances the expression ofMRP4 and then increases the VB6 transport which finally ensures the VB6 homeostasis. The results confirm that miR-3024 regulates nutrient transport in the endosymbiont–host system and is a suitable target for sustainable pest control.

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August 29, 10:39 PM

MuLAN: Mutation-driven Light Attention Networks for investigating protein-protein interactions from sequences | Brvbi | RMH (78)Scoop.it!

From www.biorxiv.org - August 28, 5:00 PM

Bacteria acquire new genes by horizontal gene transfer (HGT). Acquisition is typically mediated by mobile genetic elements (MGEs), however, beyond plasmids, bacteriophages and certain integrative conjugative elements (ICEs), the nature and diversity of MGEs is poorly understood. The bacteriumPseudomonas fluorescensSBW25 was propagated by serial transfer in the presence of filtrate obtained from garden compost communities. Genome sequencing of derived colonies revealed acquisition of three different mobile elements, each integrated immediately downstream oftmRNA. All are flanked by direct repeats and harbour a tyrosine integrase (intY), followed by a cargo of accessory genes including putative phage defence systems. Although characteristic of genomic islands, MGE–classifiers showed no matches to mobile elements. Interrogation of DNA sequence databases showed that similar elements are widespread in the genusPseudomonasand beyond, withVibrio Pathogenicity Island–1 (VPI–1) fromV. choleraebeing a notable example. Bioinformatic analyses demonstrate frequent transfer among diverse hosts. With focus on a single 55 kb element (I55) we show thatintYis necessary for excision and circularisation, that the element is incapable of autonomous horizontal transfer, but is mobilizable — in the absence of direct cell–cell contact — upon addition of community filtrate. Further analyses demonstrate that I55 enhances host fitness in the presence of community filtrate, which stems in part from ability to defend against phages.

?'s insight:

rainey pb, filtrate was obtained by passing community culture through a 0.2 μm filter, thus eliminating all cells

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August 29, 10:22 PM

MuLAN: Mutation-driven Light Attention Networks for investigating protein-protein interactions from sequences | Brvbi | RMH (82)Scoop.it!

From www.biorxiv.org - August 28, 5:00 PM

Biofilms are three-dimensional structures containing one or more bacterial species embedded in extracellular polymeric substances. Although most biofilms are stationary, Flavobacterium johnsoniae forms a motile spherical biofilm called a zorb, which is propelled by its base cells and contains a polysaccharide core. Here, we report formation of spatially organized, motile, multispecies biofilms, designated co-zorbs, that are distinguished by a core-shell structure. F. johnsoniae forms zorbs whose cells collect other bacterial species and transport them to the zorb core, forming a co-zorb. Live imaging revealed that co-zorbs also form in zebrafish, thereby demonstrating a new type of bacterial movement in vivo. This discovery opens new avenues for understanding community behaviors, the role of biofilms in bulk bacterial transport, and collective strategies for microbial success in various environments.

?'s insight:

1str, In monoculture, F. johnsoniae formed zorbs and E. coli did not. When the two species were coinoculated, they interacted and formed a structure we designate as a multispecies “co-zorb” in which the E. coli occupied the core surrounded by a shell of F. johnsoniae

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August 29, 9:46 PM

MuLAN: Mutation-driven Light Attention Networks for investigating protein-protein interactions from sequences | Brvbi | RMH (86)Scoop.it!

From www.cell.com - August 29, 9:46 PM

Microbial natural products are widely explored for their therapeutic potential. Understanding the underlying evolutionary and adaptive forces driving their production remains a fundamental question in biology. Amphiphilic cyclic lipopeptides (CLPs), a prominent category of bacterial specialized metabolites, show strong antimicrobial activity, particularly against phytopathogens. It is thus assumed that these compounds are deployed by soil- or rhizosphere-dwelling bacteria as microbial weapons in competitive natural environments. Here, we challenge this reductionist perspective and present evidence thatBacillusCLPs are prominent chemical mediators of ecological interactions. They helpBacillusto communicate, compete, defend against predators, or cooperate and establish mutualistic relationships with other (micro)organisms. Additional parallel examples are highlighted in other genera, such asPseudomonas. This broader perspective underscores the need for further investigation into the role of CLPs in shaping the adaptive strategies of key rhizobacterial species.

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surfactin

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August 29, 9:18 PM

MuLAN: Mutation-driven Light Attention Networks for investigating protein-protein interactions from sequences | Brvbi | RMH (90)Scoop.it!

From www.biorxiv.org - August 28, 5:00 PM

Lsr2-like nucleoid-associated proteins function as xenogeneic silencers (XSs) inhibiting expression of horizontally acquired, AT-rich DNA in actinobacteria. Interference with transcription factors can lead to counter-silencing of XS target promoters but typically requires promoter engineering. In this study, we developed a novel CRISPR/dCas-mediated counter-silencing (CRISPRcosi) approach by using nuclease-deficient dCas enzymes to counteract the Lsr2-like XS protein CgpS in Corynebacterium glutamicum or Lsr2 in Streptomyces venezuelae. Systematic in vivo reporter studies with dCas9 and dCas12a and various guide RNAs revealed effective counter-silencing of different CgpS target promoters in response to guide RNA/dCas DNA binding, independent of promoter sequence modifications. The most prominent CRISPRcosi effect was observed when targeting the CgpS nucleation site, an effect that was also seen in S. venezuelae when targeting a known Lsr2 nucleation site. Analyzing the system in strains lacking the XS protein CgpS revealed varying strengths of counteracting CRISPR interference effects based on the target position and strand. Genome-wide transcriptome profiling in sgRNA/dCas9 co-expressing wild-type strains revealed high counter-silencing specificity with minimal off-target effects. Thus, CRISPRcosi provides a promising system for the precise upregulation of XS target genes with significant potential for studying gene networks as well as for developing applications in biotechnology and synthetic biology.

?'s insight:

mode of regulation, 1str

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August 29, 8:46 PM

MuLAN: Mutation-driven Light Attention Networks for investigating protein-protein interactions from sequences | Brvbi | RMH (94)Scoop.it!

From www.sciencedirect.com - August 29, 8:46 PM

Certain plants and microorganisms can produce high amounts of unusual fatty acids (UFAs) such as hydroxy, conjugated, cyclic, and very long-chain polyunsaturated fatty acids, which have distinct physicochemical properties and significant applications in the food, feed, and oleochemical industries. Since many natural sources of UFAs are not ideal for large-scale agricultural production or fermentation, it is attractive to produce them through synthetic biology. Although several UFAs have been commercially or pre-commercially produced in transgenic plants and microorganisms, their contents in transgenic hosts are generally much lower than in natural sources. Moreover, reproducing this success for a wider spectrum of UFAs has remained challenging. This review discusses recent advancements in our understanding of the biosynthesis, accumulation, and heterologous production of UFAs, and addresses the challenges and potential strategies for achieving high UFA content in engineered plants and microorganisms.

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August 29, 3:41 PM

MuLAN: Mutation-driven Light Attention Networks for investigating protein-protein interactions from sequences | Brvbi | RMH (98)Scoop.it!

From www.nature.com - August 28, 5:00 PM

The remarkable capacity of bacteria to adapt in response to selective pressures drives antimicrobial resistance. Pseudomonas aeruginosa illustrates this point, establishing chronic infections during which it evolves to survive antimicrobials and evade host defenses. Many adaptive changes occur on the P. aeruginosa cell surface but methods to identify these are limited. Here we combine phage display with high-throughput DNA sequencing to create a high throughput, multiplexed technology for surveying bacterial cell surfaces, Phage-seq. By applying phage display panning to hundreds of bacterial genotypes and analyzing the dynamics of the phage display selection process, we capture important biological information about cell surfaces. This approach also yields camelid single-domain antibodies that recognize key P. aeruginosa virulence factors on live cells. These antibodies have numerous potential applications in diagnostics and therapeutics. We propose that Phage-seq establishes a powerful paradigm for studying the bacterial cell surface by identifying and profiling many surface features in parallel. Methods to identify bacterial cell surface adaptations are limited. The authors combine phage display with high-throughput DNA sequencing to create a highly-multiplexed technology for surveying bacterial cell surfaces.

?'s insight:

phage display as a tool for interrogating bacterial surface antigens.

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MuLAN: Mutation-driven Light Attention Networks for investigating protein-protein interactions from sequences | Brvbi | RMH (2024)

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