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Phage therapy is an emerging therapeutic approach for treating bacterial infections that do not respond to traditional antibiotics. The addition of phage therapy to systemic antibiotics to treat a patient with recurrent E. faecium infections that were non-responsive to antibiotics alone resulted in fewer hospitalizations and improved the patient's quality of life. Combination phage and antibiotic therapy reduced E. faecium and VRE abundance in the patient's stool. Eventually, an anti-phage antibody response emerged that was able to neutralize phage activity, which may have limited clinical efficacy. This study demonstrates the potential of phages as an additional option in the antimicrobial toolbox for treating invasive enterococcal infections and highlights the need for further investigation to ensure phage therapy can be deployed for maximum clinical benefit.

The prevalence of multidrug resistant (MDR) bacterial infections continues to rise as the development of antibiotics needed to combat these infections remains stagnant. MDR enterococci are a major contributor to this crisis. A potential therapeutic approach for combating MDR enterococci is bacteriophage (phage) therapy, which uses lytic viruses to infect and kill pathogenic bacteria. While phages that lyse some strains of MDR enterococci have been identified, other strains display high levels of resistance and the mechanisms underlying this resistance are poorly defined. Here, we use a CRISPR interference (CRISPRi) screen to identify a genetic locus found on a mobilizable plasmid from Enterococcus faecalis involved in phage resistance. This locus encodes a putative serine recombinase followed by a Type IV restriction enzyme (TIV-RE) that we show restricts the replication of phage phi47 in vancomycin-resistant E. faecalis . We further find that phi47 evolves to overcome restriction by acquiring a missense mutation in a TIV-RE inhibitor protein. We show that this inhibitor, termed t ype IV restriction i nhibiting f actor A ( tifA ), binds and inactivates diverse TIV-REs. Overall, our findings advance our understanding of phage defense in drug-resistant E. faecalis and provide mechanistic insight into how phages evolve to overcome antiphage defense systems. Using a CRISPR interference genetic approach, Bullen, Johnson, and colleagues discover a type IV restriction (TIV-RE) enzyme encoded on a mobilizable plasmid of multidrug resistant Enterococcus faecalis . This TIV-RE is a potent inhibitor of bacteriophage infection.

In this article, a block-based adaptive contrast enhancement algorithm has been proposed, which uses a modified sigmoid function for the enhancement and features extraction of electron microscopic images. The algorithm is based on a modified sigmoid function that adapts according to the input microscopic image statistics. For feature extraction, the contrast of the image is very important and authentic property by which this article enhances the visual quality of the image. In this work, for better contrast enhancement of image, a block based on input value, combined with a modified sigmoid function that is used as contrast enhancer provides better EMF values for a smaller block size. It provides localized contrast enhancement effects adaptively which is not possible using other existing techniques. Simulation and experimental results demonstrate that the proposed technique gives better results compared to other existing techniques when applied to electron microscopic images. After the enhancement of microscopic images of actinomycetes, various important features are shown, like coil or spiral, long filament, spore and rod shape structures. The proposed algorithm works efficiently for different dark and bright microscopic images.

is a Gram-positive bacterium that is resident to the intestines of animals including humans. is also an opportunistic pathogen that causes multidrug resistant (MDR) infections. Bacteriophages (phages) have been proposed as therapeutics for the treatment of MDR infections, however, an obstacle for phage therapy is the emergence of phage resistance. Despite this, the development of phage resistance can impact bacterial fitness, thus, understanding the molecular basis of fitness costs associated with phage resistance can likely be leveraged as an antimicrobial strategy. We discovered that phage resistant harbor mutations in the cell wall hydrolase gene . SagA cleaves crosslinked peptidoglycan (PG) involved in PG remodeling. We show that mutations in compromise PG hydrolysis rendering them sensitive to β-lactam antibiotics. mutants have cell envelope integrity defects, increased cellular permeability, and aberrant distribution of penicillin binding proteins. This corresponds to a growth defect where cells have abnormal division septa, membrane blebbing, and the formation of mini cells. The dysregulation of the cell envelope in mutants alters the binding of phages to the cell surface. Our data support a model where phage infection of requires phages to localize to sites of peptidoglycan remodeling at the cell poles and division septa. Our findings show that by altering the function of a single PG hydrolase, loses intrinsic β-lactam resistance. This indicates that phage therapy could help revive certain antibiotics when used in combination

The rise of antibiotic resistance motivates a revived interest in phage therapy. However, bacteria possess dozens of anti-bacteriophage immune systems that confer resistance to therapeutic phages. Chemical inhibitors of these anti-phage immune systems could be employed as adjuvants to overcome resistance in phage-based therapies. Here, we report that anti-phage systems can be selectively inhibited by small molecules, thereby sensitizing phage-resistant bacteria to phages. We discovered a class of chemical inhibitors that inhibit the type II Thoeris anti-phage immune system. These inhibitors block the biosynthesis of a histidine-ADPR intracellular 'alarm' signal by ThsB and prevent ThsA from arresting phage replication. These inhibitors promiscuously inhibit type II Thoeris systems from diverse bacteria-including antibiotic-resistant pathogens. Chemical inhibition of the Thoeris defense improved the efficacy of a model phage therapy against a phage-resistant strain of in a mouse infection, suggesting a therapeutic potential. Furthermore, these inhibitors may be employed as chemical tools to dissect the importance of the Thoeris system for phage defense in natural microbial communities.

When researchers claim AI systems possess ToM or mental models, they are fundamentally discussing behavioral predictions and bias corrections rather than genuine mental states. This position paper argues that the current discourse conflates sophisticated pattern matching with authentic cognition, missing a crucial distinction between simulation and experience. While recent studies show LLMs achieving human-level performance on ToM laboratory tasks, these results are based only on behavioral mimicry. More importantly, the entire testing paradigm may be flawed in applying individual human cognitive tests to AI systems, but assessing human cognition directly in the moment of human-AI interaction. I suggest shifting focus toward mutual ToM frameworks that acknowledge the simultaneous contributions of human cognition and AI algorithms, emphasizing the interaction dynamics, instead of testing AI in isolation.

The prevalence of multidrug resistant (MDR) bacterial infections continues to rise as the development of antibiotics needed to combat these infections remains stagnant. MDR enterococci are a major contributor to this crisis. A potential therapeutic approach for combating MDR enterococci is bacteriophage (phage) therapy, which uses lytic viruses to infect and kill pathogenic bacteria. While phages that lyse some strains of MDR enterococci have been identified, other strains display high levels of resistance and the mechanisms underlying this resistance are poorly defined. Here, we use a CRISPR interference (CRISPRi) screen to identify a genetic locus found on a mobilizable plasmid from involved in phage resistance. This locus encodes a putative serine recombinase followed by a Type IV restriction enzyme (TIV-RE) that we show restricts the replication of phage phi47 in . We further find that phi47 evolves to overcome restriction by acquiring a missense mutation in a TIV-RE inhibitor protein. We show that this inhibitor, termed type IV restriction inhibiting factor A ( ), binds and inactivates diverse TIV-REs. Overall, our findings advance our understanding of phage defense in drug-resistant and provide mechanistic insight into how phages evolve to overcome antiphage defense systems.

The rise of antibiotic resistance motivates a revived interest in phage therapy. However, bacteria possess dozens of anti-bacteriophage immune systems that confer resistance to therapeutic phages. Chemical inhibitors of these anti-phage immune systems could be employed as adjuvants to overcome resistance in phage-based therapies. Here, we report that anti-phage systems can be selectively inhibited by small molecules, thereby sensitizing phage-resistant bacteria to phages. We discovered a class of chemical inhibitors that inhibit the type II Thoeris anti-phage immune system. These inhibitors block the biosynthesis of a histidine-ADPR intracellular alarm signal by ThsB and prevent ThsA from arresting phage replication. These inhibitors promiscuously inhibit type II Thoeris systems from diverse bacteria — including antibiotic-resistant pathogens. Chemical inhibition of the Thoeris defense improved the efficacy of a model phage therapy against a phage-resistant strain of P. aeruginosa in a mouse infection, suggesting a therapeutic potential. Furthermore, these inhibitors may be employed as chemical tools to dissect the importance of the Thoeris system for phage defense in natural microbial communities.Competing Interest StatementThe authors have declared no competing interest.

Background Thermophilic cellulases are essential for effectively degrading cellulose, which is a significant part of lignocellulosic waste. In this study, we focused on a cellulase gene (~ 1.2 kb) obtained from Geobacillus sp. TP-3, a thermo-alkalophilic bacterium isolated from the hot springs of Tapovan (Uttarakhand, India). Cellulase gene (~ 1.2 kb) was amplified via PCR, cloned into pET-28a (+) vector, transferred to Escherichia coli DH5α cells and expressed in Escherichia coli BL21 (DE3). The recombinant cellulase ( rCel_TP ) was purified using Ni 2+ -NTA affinity chromatography. Results The purified rCel_TP enzyme exhibited optimal activity at 50 ºC and pH 8, displaying stability even after 3 h of incubation at 50 ºC. The molecular weight of the purified 6 × His-tagged rCel_TP was determined to be ~ 40.2 kDa. Under conditions of 50 ºC and pH 8, the kinetic parameters of the purified enzyme were determined, with K m and V max values of 116.78 mg/mL and 44.05 µmolmg −1  min −1 , respectively. The activity of the rCel_TP cellulase was significantly improved by Hg 2+ , Cu 2+ and Co 2+ . However, it was suppressed by dithiothreitol and β-mercaptoethanol. Ethylenediaminetetraacetic acid and solvents also had a slight inhibitory effect. Conclusion These results suggest the potential applications of the recombinant cellulase in biomass conversion processes for the production of fuels and other industrial operations. The study contributes valuable insights into the properties and applicability of cellulases derived from extremophilic microorganisms. Graphical abstract

In order to create eco-friendly composite materials for industries like construction and furniture, it is necessary to find substitutes for commonly used materials that harm the environment. One potential solution is to explore biopolymer alternatives to synthetic polymers. Recently, mycelium-derived products have been examined as a viable solution for large-scale production. Mycelium, which comes from fungi, particularly mushrooms, binds organic waste together and acts as an adhesive, forming a degradable substance that can take almost any shape. The material properties are influenced by factors such as the type of fungus used, the waste used as food, growth kinetics, and post-synthesis processing. These factors enable the creation of materials with desired properties such as elasticity, porosity, texture, patterns, colour, conductivity, high-temperature performance, corrosion resistance, and cost-effectiveness. These materials are widely used in building, bio-textiles, sound insulation panels, leather, and furniture. This article provides an introduction to mycelium-based materials, their synthesis, material-based design strategies, and industrial applications. Graphical abstract