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Klebsiella pneumoniae, a major clinical pathogen known for causing severe infections, is attracting heightened attention due to its escalating antibiotic resistance. Phages are emerging as a promising alternative to antibiotics; however, their specificity to particular hosts often restricts their use. In this study, a collection of 114 phages is obtained and subjected to analysis against 238 clinical K. pneumoniae strains, revealing a spectrum of lytic behaviors. A correlation between putative tail protein clusters and lysis patterns leads to the discovery of six receptor‐binding protein (RBP) clusters that determine host capsule tropism. Significantly, RBPs with cross‐capsular lysis capabilities are identified. The newly‐identified RBPs provide a toolbox for customizing phages to target diverse capsular types. Building on the toolbox, the engineered phages with altered RBPs successfully shifted and broadened their host capsule tropism, setting the stage for tunable phage that offer a precise and flexible solution to combat K. pneumoniae infections. [ABSTRACT FROM AUTHOR]

The article is a response to a previous study that inaccurately predicted the diversity of archaeal viruses in the human gut. The authors of the response explain that the computational tools used in the previous study were limited in identifying novel archaeal viral sequences because they were developed based on reference viral genomes available in public databases. The authors conducted their own analysis using different computational tools and found a great discrepancy in the results. They categorized the sequences in the database into five levels of confidence based on the results of various bioinformatic tools. They also provided a modified figure to visually demonstrate the novel contributions of the database in enhancing archaeal virus detection and classification. The authors advise using only the sequences classified as "Complete Viruses" and "High Confidence Viruses" from the database for accuracy and reliability. [Extracted from the article]

MXene, a family of two-dimensional (2D) transition metal carbides and nitrides, has intriguing electrochemical energy storage and electrocatalysis applications. Introducing the electronic metal-support interaction (EMSI) effect is one effective strategy to optimize the catalytic efficiency for MXene-based composites. However, most of the studies concentrate on optimizing the performance of metals rather than supported substrates by using this strategy. In this work, we mainly investigate the influence of an EMSI effect on the performance of the supported substrate (Ti3C2Tx MXene). Detailed scanning electrochemical microscopy and numerical simulations results reveal that the charge distribution on the Ti3C2Tx basal plane (approximate 100 nm-radius) surrounding Au nanoparticles (20 nm-radius) was significantly enhanced as a result of —O being the majority surface functional group on Ti3C2Tx that was attached to Au nanoparticle, and the related hydrogen evolution reaction (HER) activity was much better than that of the unaffected Ti3C2Tx basal plane, which even can be comparable to that of Au. This finding will be helpful for designing new strategies to enhance the overall catalytic performance of various MXene-based composites. [ABSTRACT FROM AUTHOR]

Taking advantage of asymmetric ion transport in nanopipettes, the surface charges of various substrates have been successfully imaged by scanning ion conductance microscopy (SICM). The predominant electrostatic interaction between charged nanopipettes and substrates thus needs to be better elucidated and quantified, as traditional SICM theory is not adequate to describe the resulting ion current. Herein, we use both experimental and simulation methods to study the asymmetric ion‐transport processes in nanopipettes near charged substrates, and correlate surface charge and geometry parameters to the resulting ionic current. It is found that for negatively charged substrates and nanopipettes, positive feedback responses are displayed at the high conductivity states, and they are sensitive to the applied voltages and surface charges. While at the low conductivity states, comparable negative feedback responses are largely independent of experimental conditions. The elucidated and quantified asymmetric ion transport features would allow more accurate measurements and analysis for approaching and surface charge mapping in SICM applications. [ABSTRACT FROM AUTHOR]

Overuse of antibiotics in clinical medicine has contributed to the global spread of multidrug-resistant bacterial pathogens, including Acinetobacter baumannii. We present a case of an 88-year-old Chinese man who developed hospital-acquired pneumonia caused by carbapenem-resistant A. baumannii (CRAB). A personalized lytic pathogen-specific single-phage preparation was nebulized to the patient continuously for 16 days in combination with tigecycline and polymyxin E. The treatment was well tolerated and resulted in clearance of the pathogen and clinical improvement of the patient's lung function. [ABSTRACT FROM AUTHOR]

Pseudomonas phages PaGz-1 and PaZq-1, two new phages infecting Pseudomonas aeruginosa, were isolated from fresh water in Guangdong province, China. The genomes of these two phages consist of 93,975 bp and 94,315 bp and contain 175 and 172 open reading frames (ORFs), respectively. The genome sequences of PaGz-1 and PaZq-1 share 95.8% identity with a query coverage of 94%, suggesting that these two phages belong to two different species. Based on results of nucleotide sequence alignment, gene annotation, and phylogenetic analysis, we propose PaGz-1 and PaZq-1 as representative isolates of two species in the genus Pakpunavirus within the family Myoviridae. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests that the gut microbiome actively regulates cognitive functions and that gut microbiome imbalance is associated with Alzheimer's disease (AD), the most prevalent neurodegenerative disorder. However, the changes in gut microbiome composition in AD and their association with disease pathology, especially in the early stages, are unclear. Here, we compared the profiles of gut microbiota between APP/PS1 transgenic mice (an AD mouse model) and their wild-type littermates at different ages by amplicon-based sequencing of 16S ribosomal RNA genes. Microbiota composition started diverging between the APP/PS1 and wild-type mice at young ages (i.e., 1–3 months), before obvious amyloid deposition and plaque-localized microglial activation in the cerebral cortex in APP/PS1 mice. At later ages (i.e., 6 and 9 months), there were distinct changes in the abundance of inflammation-related bacterial taxa including Escherichia-Shigella, Desulfovibrio, Akkermansia, and Blautia in APP/PS1 mice. These findings suggest that gut microbiota alterations precede the development of key pathological features of AD, including amyloidosis and plaque-localized neuroinflammation. Thus, the investigation of gut microbiota might provide new avenues for developing diagnostic biomarkers and therapeutic targets for AD. [ABSTRACT FROM AUTHOR]

Vibrio is one of the most detrimental agents of shrimp premature death syndrome. Phage therapy for prevention and treatment of Vibrio infections has attracted increasing attentions due to the emergence of antibiotic-resistant bacterial variants. Here, we describe a workflow of preparing a phage cocktail against Vibrio infections for practical applications. Twenty Vibrio strains were isolated from the gut of diseased shrimp and aquaculture wastewater, and five of them were identified as pathogens causing shrimp vibriosis. Twenty-two lytic phages were then isolated using the above five pathogens as hosts, and five of them showed broad host ranges and high lytic capability against the Vibrio strains. Whole genomic sequencing and phylogenetic analysis of the five phages indicated that they are novel and belong to the Siphoviridae family. The phage cocktail consisting of these five phages showed higher efficiency in inhibiting the growth of pathogenic Vibrio sp. Va-F3 than any single phage in vitro. We then evaluated the performance of the phage cocktail in protecting shrimp against Vibrio sp. Va-F3 infections in situ. The results showed that shrimp survival rates could reach 91.4 and 91.6% in 7 days, for the cocktail-treated and the antibiotic-treated groups, respectively. By contrast, the shrimp survival rate of the group without any treatment was only 20.0%. Overall, this study describes a general workflow of how to prepare a phage cocktail and apply it in controlling bacterial infections in the shrimp aquaculture. Knowledge gained from this study will not only help fight against the shrimp vibriosis in practical but also facilitate the design of phage cocktails with a satisfying performance in controlling other animal diseases in aquaculture. [ABSTRACT FROM AUTHOR]

Recent studies have shown that microorganisms may be associated with the onset and development of bladder cancer. The purpose of this study is to identify the common core bacteria associated with bladder cancer. We characterized the urinary microbial profile of the individuals with bladder cancer by 16S rRNA gene sequencing, and the results of 24 bladder cancer samples collected in our laboratory reveal 31 common core bacteria at genera level. In addition, the abundance of four common core bacteria is significantly higher in bladder cancer samples than in samples from nondiseased people analyzed by LEfSe, based on two previous datasets. In particular, the abundance of Acinetobacter is much higher in bladder cancer samples. It has been reported that Acinetobacter is involved not only in biofilm formation but also in the adhesion and invasion of epithelial cells, the spread of bacteria caused by the degradation of phospholipids in the mucosal barrier, and the escape of the host immune response. Thus, Acinetobacter may be related to bladder cancer and is a potential microbial marker of bladder cancer. However, due to the limited number of participants, further studies are needed to better understand the role of microorganisms in bladder cancer to provide novel biomarkers for diagnosis, prognosis, and therapy. [ABSTRACT FROM AUTHOR]

Background: Cellulose is the most abundant organic polymer mainly produced by plants in nature. It is insoluble and highly resistant to enzymatic hydrolysis. Cellulolytic microorganisms that are capable of producing a battery of related enzymes play an important role in recycling cellulose-rich plant biomass. Effective cellulose degradation by multiple synergic microorganisms has been observed within a defined microbial consortium in the lab culture. Metagenomic analysis may enable us to understand how microbes cooperate in cellulose degradation in a more complex microbial free-living ecosystem in nature. Results: Here we investigated a typical cellulose-rich and alkaline niche where constituent microbes survive through inter-genera cooperation in cellulose utilization. The niche has been generated in an ancient paper-making plant, which has served as an isolated habitat for over 7 centuries. Combined amplicon-based sequencing of 16S rRNA genes and metagenomic sequencing, our analyses showed a microbial composition with 6 dominant genera including Cloacibacterium, Paludibacter, Exiguobacterium, Acetivibrio, Tolumonas , and Clostridium in this cellulose-rich niche; the composition is distinct from other cellulose-rich niches including a modern paper mill, bamboo soil, wild giant panda guts, and termite hindguts. In total, 11,676 genes of 96 glucoside hydrolase (GH) families, as well as 1,744 genes of carbohydrate transporters were identified, and modeling analysis of two representative genes suggested that these glucoside hydrolases likely evolved to adapt to alkaline environments. Further reconstruction of the microbial draft genomes by binning the assembled contigs predicted a mutualistic interaction between the dominant microbes regarding the cellulolytic process in the niche, with Paludibacter and Clostridium acting as helpers that produce endoglucanases, and Cloacibacterium, Exiguobacterium, Acetivibrio , and Tolumonas being beneficiaries that cross-feed on the cellodextrins by oligosaccharide uptake. Conclusion: The analysis of the key genes involved in cellulose degradation and reconstruction of the microbial draft genomes by binning the assembled contigs predicted a mutualistic interaction based on public goods regarding the cellulolytic process in the niche, suggesting that in the studied microbial consortium, free-living bacteria likely survive on each other by acquisition and exchange of metabolites. Knowledge gained from this study will facilitate the design of complex microbial communities with a better performance in industrial bioprocesses. [ABSTRACT FROM AUTHOR]

As an alternative approach against multidrug-resistant bacterial infections, phages are now being increasingly investigated as effective therapeutic agents. Here, aiming to design an efficient phage cocktail against Aeromonas salmonicida infections, we isolated and characterized five lytic A. salmonicida phages, AS-szw, AS-yj, AS-zj, AS-sw, and AS-gz. The results of morphological and genomic analysis suggested that all these phages are affiliated to the T4virus genus of the Caudovirales order. Their heterogeneous lytic capacities against A. salmonicida strains were demonstrated by experiments. A series of phage cocktails were prepared and investigated in vitro. We observed that the cocktail combining AS-gz and AS-yj showed significantly higher antimicrobial activity than other cocktails and individual phages. Given the divergent genomes between the phages AS-yj and AS-gz, our results highlight that the heterogeneous mechanisms that phages use to infect their hosts likely lead to phage synergy in killing the host. Conclusively, our study described a strategy to develop an effective and promising phage cocktail as a therapeutic agent to combat A. salmonicida infections, and thereby to control the outbreak of relevant fish diseases. Our study suggests that in vitro investigations into phages are prerequisite to obtain satisfying phage cocktails prior to application in practice. [ABSTRACT FROM AUTHOR]

Progressive lung function decline is a hallmark of chronic obstructive pulmonary disease (COPD). Airway dysbiosis occurs in COPD, but whether it contributes to disease progression remains unknown. Here, we show, through a longitudinal analysis of two cohorts involving four UK centers, that baseline airway dysbiosis in COPD patients, characterized by the enrichment of opportunistic pathogenic taxa, associates with a rapid forced expiratory volume in 1 s (FEV 1) decline over 2 years. Dysbiosis associates with exacerbation-related FEV 1 fall and sudden FEV 1 fall at stability, contributing to long-term FEV 1 decline. A third cohort in China further validates the microbiota-FEV 1 -decline association. Human multi-omics and murine studies show that airway Staphylococcus aureus colonization promotes lung function decline through homocysteine, which elicits a neutrophil apoptosis-to-NETosis shift via the AKT1-S100A8/A9 axis. S. aureus depletion via bacteriophages restores lung function in emphysema mice, providing a fresh approach to slow COPD progression by targeting the airway microbiome. [Display omitted] • Baseline airway dysbiosis is associated with rapid lung function decline in COPD • Microbial-metabolite-host interactions differ in COPD rapid lung function decliners • Staphylococcus aureus impairs lung function via the homocysteine-AKT1-S100A8/A9 axis • Bacteriophage-targeting S. aureus restores lung function in emphysema mice Airway dysbiosis is associated with accelerated lung function decline, a hallmark feature in chronic obstructive pulmonary disease (COPD). Staphylococcus aureus impairs lung function via the homocysteine-AKT1-S100A8/A9 axis in emphysema mice, which can be rescued by bacteriophage targeting of this bacterium. These findings imply a translational application to slow COPD progression by targeting the microbiome. [ABSTRACT FROM AUTHOR]

Phages are highly abundant in the human gut, yet most of them remain uncultured. Here, we present a gut phage isolate collection (GPIC) containing 209 phages for 42 commensal human gut bacterial species. Genome analysis of the phages identified 34 undescribed genera. We discovered 22 phages from the Salasmaviridae family that have small genomes (∼10–20 kbp) and infect Gram-positive bacteria. Two phages from a candidate family, Paboviridae , with high prevalence in the human gut were also identified. Infection assays showed that Bacteroides and Parabacteroides phages are specific to a bacterial species, and strains of the same species also exhibit substantial variations in phage susceptibility. A cocktail of 8 phages with a broad host range for Bacteroides fragilis strains effectively reduced their abundance in complex host-derived communities in vitro. Our study expands the diversity of cultured human gut bacterial phages and provides a valuable resource for human microbiome engineering. [Display omitted] • Large-scale cultivation was used to isolate 209 phages for 42 human gut bacterial species • Genomic analysis reveals isolated phage diversity and discovers two phage families • Bacteroides and Parabacteroides strains show great variations in phage susceptibility • A phage cocktail reduces abundance of the targeted species in communities in vitro Shen et al. isolate and characterize a collection of 209 phages for human gut bacteria. They discover Salasmaviridae phages with small genomes and highly prevalent candidate Paboviridae phages. A phage cocktail reduced abundance of the targeted species in host-derived communities in vitro , suggesting their application in targeting the gut microbiome. [ABSTRACT FROM AUTHOR]