PLoS BiologyPub Date : 2024-12-05eCollection Date: 2024-12-01DOI: 10.1371/journal.pbio.3002848
Grant Kinsler, Yuping Li, Gavin Sherlock, Dmitri A Petrov
{"title":"A high-resolution two-step evolution experiment in yeast reveals a shift from pleiotropic to modular adaptation.","authors":"Grant Kinsler, Yuping Li, Gavin Sherlock, Dmitri A Petrov","doi":"10.1371/journal.pbio.3002848","DOIUrl":"10.1371/journal.pbio.3002848","url":null,"abstract":"<p><p>Evolution by natural selection is expected to be a slow and gradual process. In particular, the mutations that drive evolution are predicted to be small and modular, incrementally improving a small number of traits. However, adaptive mutations identified early in microbial evolution experiments, cancer, and other systems often provide substantial fitness gains and pleiotropically improve multiple traits at once. We asked whether such pleiotropically adaptive mutations are common throughout adaptation or are instead a rare feature of early steps in evolution that tend to target key signaling pathways. To do so, we conducted barcoded second-step evolution experiments initiated from 5 first-step mutations identified from a prior yeast evolution experiment. We then isolated hundreds of second-step mutations from these evolution experiments, measured their fitness and performance in several growth phases, and conducted whole genome sequencing of the second-step clones. Here, we found that while the vast majority of mutants isolated from the first-step of evolution in this condition show patterns of pleiotropic adaptation-improving both performance in fermentation and respiration growth phases-second-step mutations show a shift towards modular adaptation, mostly improving respiration performance and only rarely improving fermentation performance. We also identified a shift in the molecular basis of adaptation from genes in cellular signaling pathways towards genes involved in respiration and mitochondrial function. Our results suggest that the genes in cellular signaling pathways may be more likely to provide large, adaptively pleiotropic benefits to the organism due to their ability to coherently affect many phenotypes at once. As such, these genes may serve as the source of pleiotropic adaptation in the early stages of evolution, and once these become exhausted, organisms then adapt more gradually, acquiring smaller, more modular mutations.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 12","pages":"e3002848"},"PeriodicalIF":9.8,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11620474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142787434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS BiologyPub Date : 2024-12-05eCollection Date: 2024-12-01DOI: 10.1371/journal.pbio.3002887
Kota Ishibashi, Yuichi Shichino, Peixun Han, Kimi Wakabayashi, Mari Mito, Toshifumi Inada, Seisuke Kimura, Shintaro Iwasaki, Yuichiro Mishima
{"title":"Translation of zinc finger domains induces ribosome collision and Znf598-dependent mRNA decay in zebrafish.","authors":"Kota Ishibashi, Yuichi Shichino, Peixun Han, Kimi Wakabayashi, Mari Mito, Toshifumi Inada, Seisuke Kimura, Shintaro Iwasaki, Yuichiro Mishima","doi":"10.1371/journal.pbio.3002887","DOIUrl":"10.1371/journal.pbio.3002887","url":null,"abstract":"<p><p>Quality control of translation is crucial for maintaining cellular and organismal homeostasis. Obstacles in translation elongation induce ribosome collision, which is monitored by multiple sensor mechanisms in eukaryotes. The E3 ubiquitin ligase Znf598 recognizes collided ribosomes, triggering ribosome-associated quality control (RQC) to rescue stalled ribosomes and no-go decay (NGD) to degrade stall-prone mRNAs. However, the impact of RQC and NGD on maintaining the translational homeostasis of endogenous mRNAs has remained unclear. In this study, we investigated the endogenous substrate mRNAs of NGD during the maternal-to-zygotic transition (MZT) of zebrafish development. RNA-Seq analysis of zebrafish znf598 mutant embryos revealed that Znf598 down-regulates mRNAs encoding the C2H2-type zinc finger domain (C2H2-ZF) during the MZT. Reporter assays and disome profiling indicated that ribosomes stall and collide while translating tandem C2H2-ZFs, leading to mRNA degradation by Znf598. Our results suggest that NGD maintains the quality of the translatome by mitigating the risk of ribosome collision at the abundantly present C2H2-ZF sequences in the vertebrate genome.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 12","pages":"e3002887"},"PeriodicalIF":9.8,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11620358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142787439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS BiologyPub Date : 2024-12-05eCollection Date: 2024-12-01DOI: 10.1371/journal.pbio.3002480
Lily D Peck, Theo Llewellyn, Bastien Bennetot, Samuel O'Donnell, Reuben W Nowell, Matthew J Ryan, Julie Flood, Ricardo C Rodríguez de la Vega, Jeanne Ropars, Tatiana Giraud, Pietro D Spanu, Timothy G Barraclough
{"title":"Horizontal transfers between fungal Fusarium species contributed to successive outbreaks of coffee wilt disease.","authors":"Lily D Peck, Theo Llewellyn, Bastien Bennetot, Samuel O'Donnell, Reuben W Nowell, Matthew J Ryan, Julie Flood, Ricardo C Rodríguez de la Vega, Jeanne Ropars, Tatiana Giraud, Pietro D Spanu, Timothy G Barraclough","doi":"10.1371/journal.pbio.3002480","DOIUrl":"10.1371/journal.pbio.3002480","url":null,"abstract":"<p><p>Outbreaks of fungal diseases have devastated plants and animals throughout history. Over the past century, the repeated emergence of coffee wilt disease caused by the fungal pathogen Fusarium xylarioides severely impacted coffee production across sub-Saharan Africa. To improve the disease management of such pathogens, it is crucial to understand their genetic structure and evolutionary potential. We compared the genomes of 13 historic strains spanning 6 decades and multiple disease outbreaks to investigate population structure and host specialisation. We found that F. xylarioides comprised at least 4 distinct lineages: 1 host-specific to Coffea arabica, 1 to C. canephora var. robusta, and 2 historic lineages isolated from various Coffea species. The presence/absence of large genomic regions across populations, the higher genetic similarities of these regions between species than expected based on genome-wide divergence and their locations in different loci in genomes across populations showed that horizontal transfers of effector genes from members of the F. oxysporum species complex contributed to host specificity. Multiple transfers into F. xylarioides populations matched different parts of the F. oxysporum mobile pathogenicity chromosome and were enriched in effector genes and transposons. Effector genes in this region and other carbohydrate-active enzymes important in the breakdown of plant cell walls were shown by transcriptomics to be highly expressed during infection of C. arabica by the fungal arabica strains. Widespread sharing of specific transposons between F. xylarioides and F. oxysporum, and the correspondence of a putative horizontally transferred regions to a Starship (large mobile element involved in horizontal gene transfers in fungi), reinforce the inference of horizontal transfers and suggest that mobile elements were involved. Our results support the hypothesis that horizontal gene transfers contributed to the repeated emergence of coffee wilt disease.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 12","pages":"e3002480"},"PeriodicalIF":9.8,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11620798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142787437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS BiologyPub Date : 2024-12-04eCollection Date: 2024-12-01DOI: 10.1371/journal.pbio.3002935
Malthe S Nordentoft, Naoya Takahashi, Mathias S Heltberg, Mogens H Jensen, Rune N Rasmussen, Athanasia Papoutsi
{"title":"Local changes in potassium ions regulate input integration in active dendrites.","authors":"Malthe S Nordentoft, Naoya Takahashi, Mathias S Heltberg, Mogens H Jensen, Rune N Rasmussen, Athanasia Papoutsi","doi":"10.1371/journal.pbio.3002935","DOIUrl":"10.1371/journal.pbio.3002935","url":null,"abstract":"<p><p>During neuronal activity, the extracellular concentration of potassium ions ([K+]o) increases substantially above resting levels, yet it remains unclear what role these [K+]o changes play in the dendritic integration of synaptic inputs. We here used mathematical formulations and biophysical modeling to explore the role of synaptic activity-dependent K+ changes in dendritic segments of a visual cortex pyramidal neuron, receiving inputs tuned to stimulus orientation. We found that the spatial arrangement of inputs dictates the magnitude of [K+]o changes in the dendrites: Dendritic segments receiving similarly tuned inputs can attain substantially higher [K+]o increases than segments receiving diversely tuned inputs. These [K+]o elevations in turn increase dendritic excitability, leading to more robust and prolonged dendritic spikes. Ultimately, these local effects amplify the gain of neuronal input-output transformations, causing higher orientation-tuned somatic firing rates without compromising orientation selectivity. Our results suggest that local, activity-dependent [K+]o changes in dendrites may act as a \"volume knob\" that determines the impact of synaptic inputs on feature-tuned neuronal firing.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 12","pages":"e3002935"},"PeriodicalIF":9.8,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142781697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS BiologyPub Date : 2024-12-03eCollection Date: 2024-12-01DOI: 10.1371/journal.pbio.3002852
Neha Malhotra, Sangmi Oh, Peter Finin, Jessica Medrano, Jenna Andrews, Michael Goodwin, Tovah E Markowitz, Justin Lack, Helena I M Boshoff, Clifton Earl Barry
{"title":"Environmental fungi target thiol homeostasis to compete with Mycobacterium tuberculosis.","authors":"Neha Malhotra, Sangmi Oh, Peter Finin, Jessica Medrano, Jenna Andrews, Michael Goodwin, Tovah E Markowitz, Justin Lack, Helena I M Boshoff, Clifton Earl Barry","doi":"10.1371/journal.pbio.3002852","DOIUrl":"10.1371/journal.pbio.3002852","url":null,"abstract":"<p><p>Mycobacterial species in nature are found in abundance in sphagnum peat bogs where they compete for nutrients with a variety of microorganisms including fungi. We screened a collection of fungi isolated from sphagnum bogs by co-culture with Mycobacterium tuberculosis (Mtb) to look for inducible expression of antitubercular agents and identified 5 fungi that produced cidal antitubercular agents upon exposure to live Mtb. Whole genome sequencing of these fungi followed by fungal RNAseq after Mtb exposure allowed us to identify biosynthetic gene clusters induced by co-culture. Three of these fungi induced expression of patulin, one induced citrinin expression and one induced the production of nidulalin A. The biosynthetic gene clusters for patulin and citrinin have been previously described but the genes involved in nidulalin A production have not been described before. All 3 of these potent electrophiles react with thiols and treatment of Mtb cells with these agents followed by Mtb RNAseq showed that these natural products all induce profound thiol stress suggesting a rapid depletion of mycothiol. The induction of thiol-reactive mycotoxins through 3 different systems in response to exposure to Mtb suggests that fungi have identified this as a highly vulnerable target in a similar microenvironment to that of the caseous human lesion.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 12","pages":"e3002852"},"PeriodicalIF":9.8,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11614215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS BiologyPub Date : 2024-12-03eCollection Date: 2024-12-01DOI: 10.1371/journal.pbio.3002914
Simon Dellicour, Paul Bastide, Pauline Rocu, Denis Fargette, Olivier J Hardy, Marc A Suchard, Stéphane Guindon, Philippe Lemey
{"title":"How fast are viruses spreading in the wild?","authors":"Simon Dellicour, Paul Bastide, Pauline Rocu, Denis Fargette, Olivier J Hardy, Marc A Suchard, Stéphane Guindon, Philippe Lemey","doi":"10.1371/journal.pbio.3002914","DOIUrl":"10.1371/journal.pbio.3002914","url":null,"abstract":"<p><p>Genomic data collected from viral outbreaks can be exploited to reconstruct the dispersal history of viral lineages in a two-dimensional space using continuous phylogeographic inference. These spatially explicit reconstructions can subsequently be used to estimate dispersal metrics that can be informative of the dispersal dynamics and the capacity to spread among hosts. Heterogeneous sampling efforts of genomic sequences can however impact the accuracy of phylogeographic dispersal metrics. While the impact of spatial sampling bias on the outcomes of continuous phylogeographic inference has previously been explored, the impact of sampling intensity (i.e., sampling size) when aiming to characterise dispersal patterns through continuous phylogeographic reconstructions has not yet been thoroughly evaluated. In our study, we use simulations to evaluate the robustness of 3 dispersal metrics - a lineage dispersal velocity, a diffusion coefficient, and an isolation-by-distance (IBD) signal metric - to the sampling intensity. Our results reveal that both the diffusion coefficient and IBD signal metrics appear to be the most robust to the number of samples considered for the phylogeographic reconstruction. We then use these 2 dispersal metrics to compare the dispersal pattern and capacity of various viruses spreading in animal populations. Our comparative analysis reveals a broad range of IBD patterns and diffusion coefficients mostly reflecting the dispersal capacity of the main infected host species but also, in some cases, the likely signature of rapid and/or long-distance dispersal events driven by human-mediated movements through animal trade. Overall, our study provides key recommendations for the use of lineage dispersal metrics to consider in future studies and illustrates their application to compare the spread of viruses in various settings.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 12","pages":"e3002914"},"PeriodicalIF":9.8,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11614233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS BiologyPub Date : 2024-12-03eCollection Date: 2024-12-01DOI: 10.1371/journal.pbio.3002934
Corson N Areshenkoff, Anouk J de Brouwer, Daniel J Gale, Joseph Y Nashed, Jonathan Smallwood, J Randall Flanagan, Jason P Gallivan
{"title":"Distinct patterns of connectivity with the motor cortex reflect different components of sensorimotor learning.","authors":"Corson N Areshenkoff, Anouk J de Brouwer, Daniel J Gale, Joseph Y Nashed, Jonathan Smallwood, J Randall Flanagan, Jason P Gallivan","doi":"10.1371/journal.pbio.3002934","DOIUrl":"10.1371/journal.pbio.3002934","url":null,"abstract":"<p><p>Sensorimotor learning is supported by multiple competing processes that operate concurrently, making it a challenge to elucidate their neural underpinnings. Here, using human functional MRI, we identify 3 distinct axes of connectivity between the motor cortex and other brain regions during sensorimotor adaptation. These 3 axes uniquely correspond to subjects' degree of implicit learning, performance errors and explicit strategy use, and involve different brain networks situated at increasing levels of the cortical hierarchy. We test the generalizability of these neural axes to a separate form of motor learning known to rely mainly on explicit processes and show that it is only the Explicit neural axis, composed of higher-order areas in transmodal cortex, that predicts learning in this task. Together, our study uncovers multiple distinct patterns of functional connectivity with motor cortex during sensorimotor adaptation, the component processes that these patterns support, and how they generalize to other forms of motor learning.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 12","pages":"e3002934"},"PeriodicalIF":9.8,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11644839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS BiologyPub Date : 2024-12-03eCollection Date: 2024-12-01DOI: 10.1371/journal.pbio.3002867
Benedict G Hogan, Mary Caswell Stoddard
{"title":"Hyperspectral imaging in animal coloration research: A user-friendly pipeline for image generation, analysis, and integration with 3D modeling.","authors":"Benedict G Hogan, Mary Caswell Stoddard","doi":"10.1371/journal.pbio.3002867","DOIUrl":"10.1371/journal.pbio.3002867","url":null,"abstract":"<p><p>Hyperspectral imaging-a technique that combines the high spectral resolution of spectrophotometry with the high spatial resolution of photography-holds great promise for the study of animal coloration. However, applications of hyperspectral imaging to questions about the ecology and evolution of animal color remain relatively rare. The approach can be expensive and unwieldy, and we lack user-friendly pipelines for capturing and analyzing hyperspectral data in the context of animal color. Fortunately, costs are decreasing and hyperspectral imagers are improving, particularly in their sensitivity to wavelengths (including ultraviolet) visible to diverse animal species. To highlight the potential of hyperspectral imaging for animal coloration studies, we developed a pipeline for capturing, sampling, and analyzing hyperspectral data (here, in the 325 nm to 700 nm range) using avian museum specimens. Specifically, we used the pipeline to characterize the plumage colors of the King bird-of-paradise (Cicinnurus regius), Magnificent bird-of-paradise (C. magnificus), and their putative hybrid, the King of Holland's bird-of-paradise (C. magnificus x C. regius). We also combined hyperspectral data with 3D digital models to supplement hyperspectral images of each specimen with 3D shape information. Using visual system-independent methods, we found that many plumage patches on the hybrid King of Holland's bird-of-paradise are-to varying degrees-intermediate relative to those of the parent species. This was true of both pigmentary and structurally colored plumage patches. Using visual system-dependent methods, we showed that only some of the differences in plumage patches among the hybrid and its parent species would be perceivable by birds. Hyperspectral imaging is poised to become the gold standard for many animal coloration applications: comprehensive reflectance data-across the entire surface of an animal specimen-can be obtained in a matter of minutes. Our pipeline provides a practical and flexible roadmap for incorporating hyperspectral imaging into future studies of animal color.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 12","pages":"e3002867"},"PeriodicalIF":9.8,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11614258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS BiologyPub Date : 2024-12-03eCollection Date: 2024-12-01DOI: 10.1371/journal.pbio.3002945
Adam J Kucharski
{"title":"Controlling minor outbreaks is necessary to prepare for major pandemics.","authors":"Adam J Kucharski","doi":"10.1371/journal.pbio.3002945","DOIUrl":"10.1371/journal.pbio.3002945","url":null,"abstract":"<p><p>Ongoing influenza H5N1 outbreaks highlight the need for timely, scalable interventions that draw on lessons from COVID-19. In particular, successful pandemic preparedness requires early outbreak management, including effective responses targeting spillovers before there is evidence of human-to-human transmission.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 12","pages":"e3002945"},"PeriodicalIF":9.8,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS BiologyPub Date : 2024-12-02eCollection Date: 2024-12-01DOI: 10.1371/journal.pbio.3002920
Sarah Wettstadt, Francisco J Marcos-Torres, Joaquín R Otero-Asman, Alicia García-Puente, Álvaro Ortega, María A Llamas
{"title":"Bacterial TonB-dependent transducers interact with the anti-σ factor in absence of the inducing signal protecting it from proteolysis.","authors":"Sarah Wettstadt, Francisco J Marcos-Torres, Joaquín R Otero-Asman, Alicia García-Puente, Álvaro Ortega, María A Llamas","doi":"10.1371/journal.pbio.3002920","DOIUrl":"10.1371/journal.pbio.3002920","url":null,"abstract":"<p><p>Competitive bacteria like the human pathogen Pseudomonas aeruginosa can acquire iron from different iron carriers, which are usually internalized via outer membrane TonB-dependent receptors (TBDRs). Production of TBDRs is promoted by the presence of the substrate. This regulation often entails a signal transfer pathway known as cell-surface signaling (CSS) that involves the TBDR itself that also functions as transducer (and is thus referred to as TBDT), a cytoplasmic membrane-bound anti-σ factor, and an extracytoplasmic function σ (σECF) factor. TBDTs contain an extra N-terminal domain known as signaling domain (SD) required for the signal transfer activity of these receptors. In the current CSS model, presence of the signal allows the interaction between the TBDT and the anti-σ factor in the periplasm, promoting the proteolysis of the anti-σ factor and in turn the σECF-dependent transcription of response genes, including the TBDT gene. However, recent evidence shows that σECF activity does not depend on this interaction, suggesting that the contact between these 2 proteins fulfills a different role. Using the P. aeruginosa Fox CSS system as model, we show here that the SD of the FoxA TBDT already interacts with the C-terminal domain of the FoxR anti-σ factor in absence of the signal. This interaction protects FoxR from proteolysis in turn preventing transcription of σFoxI-dependent genes. By structural modeling of the FoxR/FoxASD interaction, we have identified the interaction sites between these 2 proteins and provide the molecular details of this interaction. We furthermore show that to exert this protective role, FoxA undergoes proteolytic cleavage, denoting a change in the paradigm of the current CSS model.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 12","pages":"e3002920"},"PeriodicalIF":9.8,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11637429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142773999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}