Proceedings of the National Academy of Sciences of the United States of America最新文献

{"title":"Lanthanide binding peptide surfactants at air–aqueous interfaces for interfacial separation of rare earth elements","authors":"Luis E. Ortuno Macias, Felipe Jiménez-Ángeles, Jason G. Marmorstein, Yiming Wang, Stephen A. Crane, Surabh K. T., Pan Sun, Bikash Sapkota, Eshe Hummingbird, Woojin Jung, Baofu Qiao, Daeyeon Lee, Ivan J. Dmochowski, Robert J. Messinger, Mark L. Schlossman, Cesar de la Fuente-Nunez, Ravi Radhakrishnan, E. James Petersson, Monica Olvera de la Cruz, Wei Bu, Mrinal Bera, Binhua Lin, Raymond S. Tu, Kathleen J. Stebe, Charles Maldarelli","doi":"10.1073/pnas.2411763121","DOIUrl":"https://doi.org/10.1073/pnas.2411763121","url":null,"abstract":"Rare earth elements (REEs) are critical materials to modern technologies. They are obtained by selective separation from mining feedstocks consisting of mixtures of their trivalent cation. We are developing an all-aqueous, bioinspired, interfacial separation using peptides as amphiphilic molecular extractants. Lanthanide binding tags (LBTs) are amphiphilic peptide sequences based on the EF-hand metal binding loops of calcium-binding proteins which complex selectively REEs. We study LBTs optimized for coordination to Tb <jats:sup>3+</jats:sup> using luminescence spectroscopy, surface tensiometry, X-ray reflectivity, and X-ray fluorescence near total reflection, and find that these LBTs capture Tb <jats:sup>3+</jats:sup> in bulk and adsorb the complex to the interface. Molecular dynamics show that the binding pocket remains intact upon adsorption. We find that, if the net negative charge on the peptide results in a negatively charged complex, excess cations are recruited to the interface by nonselective Coulombic interactions that compromise selective REE capture. If, however, the net negative charge on the peptide is −3, resulting in a neutral complex, a 1:1 surface ratio of cation to peptide is achieved. Surface adsorption of the neutral peptide complexes from an equimolar mixture of Tb <jats:sup>3+</jats:sup> and La <jats:sup>3+</jats:sup> demonstrates a switchable platform dictated by bulk and interfacial effects. The adsorption layer becomes enriched in the favored Tb <jats:sup>3+</jats:sup> when the bulk peptide is saturated, but selective to La <jats:sup>3+</jats:sup> for undersaturation due to a higher surface activity of the La <jats:sup>3+</jats:sup> complex.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"1 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142858537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Majorana quasiparticles and topological phases in 3D active nematics","authors":"Louise C. Head, Giuseppe Negro, Livio N. Carenza, Nathan Johnson, Ryan R. Keogh, Giuseppe Gonnella, Alexander Morozov, Enzo Orlandini, Tyler N. Shendruk, Adriano Tiribocchi, Davide Marenduzzo","doi":"10.1073/pnas.2405304121","DOIUrl":"https://doi.org/10.1073/pnas.2405304121","url":null,"abstract":"Quasiparticles are low-energy excitations with important roles in condensed matter physics. An intriguing example is provided by Majorana quasiparticles, which are equivalent to their antiparticles. Despite being implicated in neutrino oscillations and topological superconductivity, their experimental realizations remain very rare. Here, we propose a purely classical realization of Majorana fermions in terms of three-dimensional disclination lines in active nematics. The underlying reason is the well-known equivalence, in 3D, between a <jats:inline-formula> <mml:math xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" display=\"inline\" overflow=\"scroll\"> <mml:mrow> <mml:mo>+</mml:mo> <mml:mn>1</mml:mn> <mml:mo stretchy=\"false\">/</mml:mo> <mml:mn>2</mml:mn> </mml:mrow> </mml:math> </jats:inline-formula> local defect profile and a <jats:inline-formula> <mml:math xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" display=\"inline\" overflow=\"scroll\"> <mml:mrow> <mml:mo>−</mml:mo> <mml:mn>1</mml:mn> <mml:mo stretchy=\"false\">/</mml:mo> <mml:mn>2</mml:mn> </mml:mrow> </mml:math> </jats:inline-formula> profile, which acts as its antiparticle. The mapping also requires proving that defect profiles transform as spinors, and activity is needed to overcome the elastic cost associated with these excitations, so they spontaneously appear in steady state. We combine topological considerations and numerics to show that active nematics under confinement spontaneously create in their interior topologically charged disclination lines and loops, akin to Majorana quasiparticles with finite momentum. Within a long channel, the phenomenology we observe resembles that of the Kitaev chain, as Majorana-like states appear near the boundaries, while a delocalized topological excitation arises in the form of a chiral disclination line. The analogy between 3D nematic defects and topological quasiparticles further suggests that active turbulence can be viewed as a topological phase, where defects percolate to form delocalized topological quasiparticles similar to those observed in the channel. We propose that three-dimensional active disclinations can be used to probe the physics of Majorana spinors at much larger scale than that for which they were originally introduced, potentially facilitating their experimental study.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"428 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142858536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toward optimal disease surveillance with graph-based active learning","authors":"Joseph L.-H. Tsui, Mengyan Zhang, Prathyush Sambaturu, Simon Busch-Moreno, Marc A. Suchard, Oliver G. Pybus, Seth Flaxman, Elizaveta Semenova, Moritz U. G. Kraemer","doi":"10.1073/pnas.2412424121","DOIUrl":"https://doi.org/10.1073/pnas.2412424121","url":null,"abstract":"Tracking the spread of emerging pathogens is critical to the design of timely and effective public health responses. Policymakers face the challenge of allocating finite resources for testing and surveillance across locations, with the goal of maximizing the information obtained about the underlying trends in prevalence and incidence. We model this decision-making process as an iterative node classification problem on an undirected and unweighted graph, in which nodes represent locations and edges represent movement of infectious agents among them. To begin, a single node is randomly selected for testing and determined to be either infected or uninfected. Test feedback is then used to update estimates of the probability of unobserved nodes being infected and to inform the selection of nodes for testing at the next iterations, until certain test budget is exhausted. Using this framework, we evaluate and compare the performance of previously developed active learning policies for node selection, including Node Entropy and Bayesian Active Learning by Disagreement. We explore the performance of these policies under different outbreak scenarios using simulated outbreaks on both synthetic and empirical networks. Further, we propose a policy that considers the distance-weighted average entropy of infection predictions among neighbors of each candidate node. Our proposed policy outperforms existing ones in most outbreak scenarios given small test budgets, highlighting the need to consider an exploration–exploitation trade-off in policy design. Our findings could inform the design of cost-effective surveillance strategies for emerging and endemic pathogens and reduce uncertainties associated with early risk assessments in resource-constrained situations.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"24 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142858494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mantle oxidation by sulfur drives the formation of giant gold deposits in subduction zones","authors":"Deng-Yang He, Kun-Feng Qiu, Adam C. Simon, Gleb S. Pokrovski, Hao-Cheng Yu, James A. D. Connolly, Shan-Shan Li, Simon Turner, Qing-Fei Wang, Meng-Fan Yang, Jun Deng","doi":"10.1073/pnas.2404731121","DOIUrl":"https://doi.org/10.1073/pnas.2404731121","url":null,"abstract":"Oxidation of the sub-arc mantle driven by slab-derived fluids has been hypothesized to contribute to the formation of gold deposits in magmatic arc environments that host the majority of metal resources on Earth. However, the mechanism by which the infiltration of slab-derived fluids into the mantle wedge changes its oxidation state and affects Au enrichment remains poorly understood. Here, we present the results of a numerical model that demonstrates that slab-derived fluids introduce large amounts of sulfate (S <jats:sup>6+</jats:sup> ) into the overlying mantle wedge that increase its oxygen fugacity by up to 3 to 4 log units relative to the pristine mantle. Our model predicts that as much as 1 wt.% of the total dissolved sulfur in slab-derived fluids reacting with mantle rocks is present as the trisulfur radical ion, S <jats:sub>3</jats:sub> <jats:sup>–</jats:sup> . This sulfur ligand stabilizes the aqueous Au(HS)S <jats:sub>3</jats:sub> <jats:sup>–</jats:sup> complex, which can transport Au concentrations of several grams per cubic meter of fluid. Such concentrations are more than three orders of magnitude higher than the average abundance of Au in the mantle. Our data thus demonstrate that an aqueous fluid phase can extract 10 to 100 times more Au than in a fluid-absent rock-melt system during mantle partial melting at redox conditions close to the sulfide-sulfate boundary. We conclude that oxidation by slab-derived fluids is the primary cause of Au mobility and enrichment in the mantle wedge and that aqueous fluid-assisted mantle melting is a prerequisite for formation of Au-rich magmatic hydrothermal and orogenic gold systems in subduction zone settings.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"114 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142858543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NPR1 promotes blue light–induced plant photomorphogenesis by ubiquitinating and degrading PIF4","authors":"Yangyang Zhou, Pengtao Liu, Yaqi Tang, Jie Liu, Yaru Tang, Yumeng Zhuang, Xiaoting Li, Kaiqi Xu, Zhi Zhou, Jigang Li, Guangming He, Xing Wang Deng, Li Yang","doi":"10.1073/pnas.2412755121","DOIUrl":"https://doi.org/10.1073/pnas.2412755121","url":null,"abstract":"Light is a major determinant of plant growth and survival. NONEXPRESSER OF PATHOGENESIS-RELATED GENES 1 (NPR1) acts as a receptor for salicylic acid (SA) and serves as the key regulator of SA-mediated immune responses. However, the mechanisms by which plants integrate light and SA signals in response to environmental changes, as well as the role of NPR1 in regulating plant photomorphogenesis, remain poorly understood. This study shows that SA promotes plant photomorphogenesis by regulating PHYTOCHROME INTERACTING FACTOR 4 (PIF4). Specifically, NPR1 promotes photomorphogenesis under blue light by facilitating the degradation of PIF4 through light-induced polyubiquitination. NPR1 acts as a substrate adaptor for the CULLIN3-based E3 ligase, which ubiquitinates PIF4 at Lys129, Lys252, and Lys428, and leading to PIF4 degradation via the 26S proteasome pathway. Genetically, <jats:italic>PIF4</jats:italic> is epistatic to <jats:italic>NPR1</jats:italic> in the regulation of blue light–induced photomorphogenesis, suggesting it acts downstream of NPR1. Furthermore, cryptochromes mediate the polyubiquitination of PIF4 by NPR1 in response to blue light by promoting the interaction and ubiquitination between NPR1 and PIF4. Transcriptome analysis revealed that under blue light, NPR1 and PIF4 coordinately regulate numerous downstream genes related to light and auxin signaling pathways. Overall, these findings unveil a role for NPR1 in photomorphogenesis, highlighting a mechanism for posttranslational regulation of PIF4 in response to blue light. This mechanism plays a pivotal role in the fine-tuning of plant development, enabling plants to adapt to complex environmental changes.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"844 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142858534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyperosmolarity-induced suppression of group B1 Raf-like protein kinases modulates drought-growth trade-off in Arabidopsis","authors":"Yoshiaki Kamiyama, Sotaro Katagiri, Yangdan Li, Kota Yamashita, Hinano Takase, Taishi Umezawa","doi":"10.1073/pnas.2419204121","DOIUrl":"https://doi.org/10.1073/pnas.2419204121","url":null,"abstract":"When plants are exposed to drought stress, there is a trade-off between plant growth and stress responses. Here, we identified a signaling mechanism for the initial steps of the drought-growth trade-off. Phosphoproteomic profiling revealed that Raf13, a B1 subgroup Raf-like kinase, is dephosphorylated under drought conditions. Raf13 and the related B1-Raf Raf15 are required for growth rather than the acquisition of osmotolerance. We also found that Raf13 interacts with B55-family regulatory subunits of protein phosphatase 2A (PP2A), which mediates hyperosmolarity-induced dephosphorylation of Raf13. In addition, Raf13 interacts with an AGC kinase INCOMPLETE ROOT HAIR ELONGATION HOMOLOG 1 (IREH1), and Raf13 and IREH1 have similar functions in regulating cellular responses that promote plant growth. Overall, our results support a model in which Raf13-IREH1 activity promotes growth under nonstressed conditions, whereas PP2A activity suppresses Raf13-IREH1 during osmotic stress to modulate the physiological “trade-off” between plant growth and stress responses.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"24 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142858542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metapopulation heterogeneities in host mobility, productivity, and immunocompetency always increase virulence and infectiousness","authors":"Masato Sato, Ulf Dieckmann, Akira Sasaki","doi":"10.1073/pnas.2309272121","DOIUrl":"https://doi.org/10.1073/pnas.2309272121","url":null,"abstract":"The epidemiology and evolution of diseases unfold in populations that are rarely homogeneous. Instead, hosts infected by pathogens often form metapopulations, in which local populations connected by the movement of hosts experience different demographic and epidemiological conditions. Here, we develop a general theory of the evolution of pathogens in heterogeneous metapopulations. We reveal the following key insights into the evolution of pathogen virulence and infectiousness: (1) When the mobility (movement rate), productivity (birth rate and carrying capacity), or immunocompetency (immunity-loss rate) differ among local populations, this variance always increases pathogen virulence and infectiousness (2) The increment of pathogen virulence caused by such heterogeneity is approximately proportional to the variance of the corresponding heterogeneous local conditions (3) This increment can be expressed as the covariance between the local selection pressures and the local reproductive values experienced by the pathogen (4) The reason why heterogeneity always increases pathogen virulence is explained by the positive correlation of local selection pressures with reproductive values (5) Combinations of multiple independent heterogeneities further increase virulence and infectiousness, even more so when their covariances are positive. Our key findings robustly hold for different epidemiological frameworks – including SI, SIS, SIR, and SIRS models, with both density- and frequency-dependent transmission as well as with superinfection. They provide insights into the risks of growing pathogen infectiousness in a world in which heterogeneity – caused, e.g., by the concentration of human populations in urban areas – is rising.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"39 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142858544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alveolar macrophages are early targets of mumps virus","authors":"Aum R. Patel, Amit Garg, Haylen T. Rosberger, Shreyas Kowdle, Rebecca A. Reis, Justin J. Frere, Megan N. Januska, Gbalekan Dawodu, Estefania Valencia, Min-Chi Yang, Christian S. Stevens, Vishal N. Rao, Griffin D. Haas, Ya-Wen Chen, Benhur Lee, Jean K. Lim","doi":"10.1073/pnas.2410954121","DOIUrl":"https://doi.org/10.1073/pnas.2410954121","url":null,"abstract":"Formerly a common childhood pathogen, mumps virus (MuV) remains active worldwide, despite relatively high vaccine coverage. MuV is thought to infect the upper respiratory tract before disseminating to other organs; however, the early cellular targets of MuV in vivo are unknown. To address this, we generated a green fluorescent protein (GFP)-tagged vaccine strain (JL5) of MuV to infect leukocytic cell lines and found that replication was greatest in monocytes. Infection of peripheral blood mononuclear cells (PBMCs) also showed that both JL5 and a circulating strain of MuV (Iowa 2006; genotype G), preferentially infected monocytes. Further, monocyte-derived macrophages showed high susceptibility to MuV, with genotype G infecting macrophages to a much greater extent. While mice are generally resistant to MuV infection, we inoculated immunocompetent Rosa26-tdTomato mice intranasally with a GFP and Cre recombinase tagged MuV to determine whether monocytes/macrophages are important targets in vivo. We observed a small population of tdTomato <jats:sup>+</jats:sup> cells within the lungs, which included epithelial cells; however, the vast majority were alveolar macrophages (AMs). To validate these findings, we infected murine AMs isolated from Rosa26-tdTomato mice with the GFP and Cre recombinase tagged MuV and found that while MuV could enter AMs, as determined by tdTomato positivity, only a small percentage of these expressed GFP, suggesting that inhibition in murine cells occurs postentry. To translate these findings, we infected cells from human bronchoalveolar lavage fluid with MuV and found that most infected cells were AMs. These findings highlight the high susceptibility of AMs and provide a basis for early MuV pathogenesis and subsequent dissemination.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"56 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142858546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stimulus-invariant aspects of the retinal code drive discriminability of natural scenes","authors":"Benjamin D. Hoshal, Caroline M. Holmes, Kyle Bojanek, Jared M. Salisbury, Michael J. Berry, Olivier Marre, Stephanie E. Palmer","doi":"10.1073/pnas.2313676121","DOIUrl":"https://doi.org/10.1073/pnas.2313676121","url":null,"abstract":"Everything that the brain sees must first be encoded by the retina, which maintains a reliable representation of the visual world in many different, complex natural scenes while also adapting to stimulus changes. This study quantifies whether and how the brain selectively encodes stimulus features about scene identity in complex naturalistic environments. While a wealth of previous work has dug into the static and dynamic features of the population code in retinal ganglion cells (RGCs), less is known about how populations form both flexible and reliable encoding in natural moving scenes. We record from the larval salamander retina responding to five different natural movies, over many repeats, and use these data to characterize the population code in terms of single-cell fluctuations in rate and pairwise couplings between cells. Decomposing the population code into independent and cell–cell interactions reveals how broad scene structure is encoded in the retinal output. while the single-cell activity adapts to different stimuli, the population structure captured in the sparse, strong couplings is consistent across natural movies as well as synthetic stimuli. We show that these interactions contribute to encoding scene identity. We also demonstrate that this structure likely arises in part from shared bipolar cell input as well as from gap junctions between RGCs and amacrine cells.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"11 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142858547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microscopic phage adsorption assay: High-throughput quantification of virus particle attachment to host bacterial cells","authors":"Jyot D. Antani, Timothy Ward, Thierry Emonet, Paul E. Turner","doi":"10.1073/pnas.2410905121","DOIUrl":"https://doi.org/10.1073/pnas.2410905121","url":null,"abstract":"Phages, viruses of bacteria, play a pivotal role in Earth’s biosphere and hold great promise as therapeutic and diagnostic tools in combating infectious diseases. Attachment of phages to bacterial cells is a crucial initial step of the interaction. The classic assay to quantify the dynamics of phage attachment involves coculturing and enumeration of bacteria and phages, which is laborious, lengthy, hence low-throughput, and only provides ensemble estimates of model-based adsorption rate constants. Here, we utilized fluorescence microscopy and particle tracking to obtain trajectories of individual virus particles interacting with cells. The trajectory durations quantified the heterogeneity in dwell time, the time that each phage spends interacting with a bacterium. The average dwell time strongly correlated with the classically measured adsorption rate constant. We successfully applied this technique to quantify host-attachment dynamics of several phages including those targeting key bacterial pathogens. This approach should benefit the field of phage biology by providing highly quantitative, model-free readouts at single-virus resolution, helping to uncover single-virus phenomena missed by traditional measurements. Owing to significant reduction in manual effort, our method should enable rapid, high-throughput screening of a phage library against a target bacterial strain for applications such as therapy or diagnosis.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"40 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142858495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}