PLoS Biology最新文献

{"title":"Engineering microbiomes for enhanced bioremediation.","authors":"Xihui Xu, Jiandong Jiang","doi":"10.1371/journal.pbio.3002951","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002951","url":null,"abstract":"<p><p>Bioremediation using synthetic microbiomes offers significant advantages over traditional single-strain-based approaches. In this Perspective, we outline 5 important considerations for the rational design of pollutant-degrading microbiomes for enhanced bioremediation.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 12","pages":"e3002951"},"PeriodicalIF":9.8,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142840182","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}

{"title":"The conserved noncoding RNA ModT coordinates growth and virulence in Clostridioides difficile.","authors":"Tina Lenče, Johannes Sulzer, Kilian Andress, Anne-Sophie Gribling-Burrer, Vanessa Lamm-Schmidt, Lars Barquist, Redmond P Smyth, Franziska Faber","doi":"10.1371/journal.pbio.3002948","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002948","url":null,"abstract":"<p><p>Bacterial noncoding RNAs fulfill a variety of cellular functions as catalysts, as scaffolds in protein complexes or as regulators of gene expression. They often exhibit complex tertiary structures that are a key determinant of their biochemical function. Here, we characterize the structured \"raiA motif\" RNA from Clostridioides difficile, which is conserved in more than 2,500 bacterial species from the phyla Bacillota and Actinomycetota. We show that its transcript abundance and stability in exponentially growing bacteria rivals that of ribosomal RNAs. Deletion of the \"raiA motif\" RNA is associated with delayed transition into stationary phase, and changes in stationary phase pathways such as spore formation, hence we rename it ModT (modulator of transition phase). Mechanistically, we show that ModT-mediated changes in cellular cyclic di-GMP levels are linked to the pronounced sporulation defect in the modT mutant. Importantly, we show that expression profiles and isoform patterns of ModT are conserved in Clostridium perfringens and Paeniclostridium sordellii, and that these orthologs can functionally complement ModT in C. difficile. Chemical structure probing of ModT in vivo reveals dynamic refolding and provides initial evidence for a potential association of ModT with proteins. In summary, our findings indicate that ModT fulfills a conserved role in regulating growth transitions in bacteria and provide a crucial step towards delineating its molecular mechanism.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 12","pages":"e3002948"},"PeriodicalIF":9.8,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822600","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}

{"title":"Novel kinase regulators of extracellular matrix internalisation identified by high-content screening modulate invasive carcinoma cell migration.","authors":"Montserrat Llanses Martinez, Keqian Nan, Zhe Bao, Rachele Bacchetti, Shengnan Yuan, Joe Tyler, Xavier Le Guezennec, Frederic A Bard, Elena Rainero","doi":"10.1371/journal.pbio.3002930","DOIUrl":"10.1371/journal.pbio.3002930","url":null,"abstract":"<p><p>The interaction between cancer cells and the extracellular matrix (ECM) plays a pivotal role in tumour progression. While the extracellular degradation of ECM proteins has been well characterised, ECM endocytosis and its impact on cancer cell progression, migration, and metastasis is poorly understood. ECM internalisation is increased in invasive breast cancer cells, suggesting it may support invasiveness. However, current high-throughput approaches mainly focus on cells grown on plastic in 2D, making it difficult to apply these to the study of ECM dynamics. Here, we developed a high-content screening assay to study ECM uptake, based on the of use automated ECM coating for the generation of highly homogeneous ECM a pH-sensitive dye to image ECM trafficking in live cells. We identified that mitogen-activated protein kinase (MAPK) family members, MAP3K1 and MAPK11 (p38β), and the protein phosphatase 2 (PP2) subunit PPP2R1A were required for the internalisation of ECM-bound α2β1 integrin. Mechanistically, we show that down-regulation of the sodium/proton exchanger 1 (NHE1), an established macropinocytosis regulator and a target of p38, mediated ECM macropinocytosis. Moreover, disruption of α2 integrin, MAP3K1, MAPK11, PPP2R1A, and NHE1-mediated ECM internalisation significantly impaired cancer cell migration and invasion in 2D and 3D culture systems. Of note, integrin-bound ECM was targeted for lysosomal degradation, which was required for cell migration on cell-derived matrices. Finally, α2β1 integrin and MAP3K1 expression were significantly up-regulated in pancreatic tumours and correlated with poor prognosis in pancreatic cancer patients. Strikingly, MAP3K1, MAPK11, PPP2R1A, and α2 integrin expression were higher in chemotherapy-resistant tumours in breast cancer patients. Our results identified the α2β1 integrin/p38 signalling axis as a novel regulator of ECM endocytosis, which drives invasive migration and tumour progression, demonstrating that our high-content screening approach has the capability of identifying novel regulators of cancer cell invasion.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 12","pages":"e3002930"},"PeriodicalIF":9.8,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11637276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819560","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}

{"title":"Genome size influences plant growth and biodiversity responses to nutrient fertilization in diverse grassland communities.","authors":"Joseph A Morton, Carlos Alberto Arnillas, Lori Biedermann, Elizabeth T Borer, Lars A Brudvig, Yvonne M Buckley, Marc W Cadotte, Kendi Davies, Ian Donohue, Anne Ebeling, Nico Eisenhauer, Catalina Estrada, Sylvia Haider, Yann Hautier, Anke Jentsch, Holly Martinson, Rebecca L McCulley, Xavier Raynaud, Christiane Roscher, Eric W Seabloom, Carly J Stevens, Katerina Vesela, Alison Wallace, Ilia J Leitch, Andrew R Leitch, Erika I Hersch-Green","doi":"10.1371/journal.pbio.3002927","DOIUrl":"10.1371/journal.pbio.3002927","url":null,"abstract":"<p><p>Experiments comparing diploids with polyploids and in single grassland sites show that nitrogen and/or phosphorus availability influences plant growth and community composition dependent on genome size; specifically, plants with larger genomes grow faster under nutrient enrichments relative to those with smaller genomes. However, it is unknown if these effects are specific to particular site localities with speciifc plant assemblages, climates, and historical contingencies. To determine the generality of genome size-dependent growth responses to nitrogen and phosphorus fertilization, we combined genome size and species abundance data from 27 coordinated grassland nutrient addition experiments in the Nutrient Network that occur in the Northern Hemisphere across a range of climates and grassland communities. We found that after nitrogen treatment, species with larger genomes generally increased more in cover compared to those with smaller genomes, potentially due to a release from nutrient limitation. Responses were strongest for C3 grasses and in less seasonal, low precipitation environments, indicating that genome size effects on water-use-efficiency modulates genome size-nutrient interactions. Cumulatively, the data suggest that genome size is informative and improves predictions of species' success in grassland communities.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 12","pages":"e3002927"},"PeriodicalIF":9.8,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814740","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}

{"title":"Public engagement with research reproducibility.","authors":"Constant Vinatier, Magdalena Kozula, Veerle Van den Eynden, Laura Caquelin, Hynek Roubik, Inge Stegeman, Florian Naudet","doi":"10.1371/journal.pbio.3002953","DOIUrl":"10.1371/journal.pbio.3002953","url":null,"abstract":"<p><p>Public engagement with reproducibility is crucial for fostering trust in science. This Community Page outlines, through the example of baking Christmas tree meringues, how scientists can effectively engage and educate the public about the importance of reproducibility in research.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 12","pages":"e3002953"},"PeriodicalIF":9.8,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814743","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}

{"title":"Quantitative perturbation-phenotype maps reveal nonlinear responses underlying robustness of PAR-dependent asymmetric cell division.","authors":"Nelio T L Rodrigues, Tom Bland, KangBo Ng, Nisha Hirani, Nathan W Goehring","doi":"10.1371/journal.pbio.3002437","DOIUrl":"10.1371/journal.pbio.3002437","url":null,"abstract":"<p><p>A key challenge in the development of an organism is to maintain robust phenotypic outcomes in the face of perturbation. Yet, it is often unclear how such robust outcomes are encoded by developmental networks. Here, we use the Caenorhabditis elegans zygote as a model to understand sources of developmental robustness during PAR polarity-dependent asymmetric cell division. By quantitatively linking alterations in protein dosage to phenotype in individual embryos, we show that spatial information in the zygote is read out in a highly nonlinear fashion and, as a result, phenotypes are highly canalized against substantial variation in input signals. Our data point towards robustness of the conserved PAR polarity network that renders polarity axis specification resistant to variations in both the strength of upstream symmetry-breaking cues and PAR protein dosage. Analogously, downstream pathways involved in cell size and fate asymmetry are robust to dosage-dependent changes in the local concentrations of PAR proteins, implying nontrivial complexity in translating PAR concentration profiles into pathway outputs. We propose that these nonlinear signal-response dynamics between symmetry-breaking, PAR polarity, and asymmetric division modules effectively insulate each individual module from variation arising in others. This decoupling helps maintain the embryo along the correct developmental trajectory, thereby ensuring that asymmetric division is robust to perturbation. Such modular organization of developmental networks is likely to be a general mechanism to achieve robust developmental outcomes.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 12","pages":"e3002437"},"PeriodicalIF":9.8,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11627365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142802880","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}

{"title":"Regulatory networks may evolve to favor adaptive foresight.","authors":"Alejandro Couce","doi":"10.1371/journal.pbio.3002922","DOIUrl":"10.1371/journal.pbio.3002922","url":null,"abstract":"<p><p>Pleiotropy-a single mutation altering many traits-has long been seen as hindering adaptation. A new study in PLOS Biology offers a striking counterexample, suggesting that regulatory networks may evolve to ensure mutations are simultaneously beneficial in correlated environments.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 12","pages":"e3002922"},"PeriodicalIF":9.8,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11623561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142789687","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}

{"title":"Not just a garbage truck: No-go decay plays a role during embryo development in zebrafish.","authors":"Alana R Plastrik, Hani S Zaher","doi":"10.1371/journal.pbio.3002925","DOIUrl":"10.1371/journal.pbio.3002925","url":null,"abstract":"<p><p>In eukaryotes, defective mRNAs that impede the movement of the ribosome are subject to rapid decay via no-go decay (NGD). In this issue of PLOS Biology, Ishibashi and colleagues expand on the role of NGD and reveal new endogenous targets for the process in zebrafish.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 12","pages":"e3002925"},"PeriodicalIF":9.8,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11623483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142789686","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}

{"title":"Gene transfer between fungal species triggers repeated coffee wilt disease outbreaks.","authors":"Brenda D Wingfield, Michael J Wingfield","doi":"10.1371/journal.pbio.3002901","DOIUrl":"10.1371/journal.pbio.3002901","url":null,"abstract":"<p><p>Two outbreaks of coffee wilt disease have devastated African coffee production. A PLOS Biology study suggests that horizontal gene transfer via large Starship transposons between 2 fungal species played a key role in the repeated emergence of the disease.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 12","pages":"e3002901"},"PeriodicalIF":9.8,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11623449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142789683","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}

{"title":"Copy number variants underlie major selective sweeps in insecticide resistance genes in Anopheles arabiensis.","authors":"Eric R Lucas, Sanjay C Nagi, Bilali Kabula, Bernard Batengana, William Kisinza, Alexander Egyir-Yawson, John Essandoh, Sam Dadzie, Joseph Chabi, Arjen E Van't Hof, Emily J Rippon, Dimitra Pipini, Nicholas J Harding, Naomi A Dyer, Chris S Clarkson, Alistair Miles, David Weetman, Martin J Donnelly","doi":"10.1371/journal.pbio.3002898","DOIUrl":"10.1371/journal.pbio.3002898","url":null,"abstract":"<p><p>To keep ahead of the evolution of resistance to insecticides in mosquitoes, national malaria control programmes must make use of a range of insecticides, both old and new, while monitoring resistance mechanisms. The outdoor-biting malaria vector Anopheles arabiensis is of increasing concern for malaria transmission because it is apparently less susceptible to many indoor control interventions, yet knowledge of its mechanisms of resistance remains limited. Furthermore, comparatively little is known in general about resistance to non-pyrethroid insecticides such as pirimiphos-methyl (PM), which are crucial for effective control in the context of globally high resistance to pyrethroids. We performed a genome-wide association study to determine the molecular mechanisms of resistance to the pyrethroid deltamethrin (commonly used in bednets) and PM (widespread use for indoor spraying), in An. arabiensis from 2 regions in Tanzania. Genomic regions of positive selection in these populations were largely driven by copy number variants (CNVs) in gene families involved in metabolic resistance. We found evidence of a new gene cluster involved in resistance to PM, identifying a strong selective sweep tied to a CNV in the carboxylesterase genes Coeae2g - Coeae6g. Using complementary data from another malaria vector, An. coluzzii, in Ghana, we show that copy number at this locus is significantly associated with PM resistance. Similarly, for deltamethrin, resistance was strongly associated with a novel CNV allele in the Cyp6aa / Cyp6p cluster (Cyp6aap_Dup33). Against this background of metabolic resistance, resistance caused by mutations in the insecticide target sites was very rare or absent. Mutations in the pyrethroid target site Vgsc were at very low frequency in Tanzania, yet combining these samples with 3 An. arabiensis individuals from West Africa revealed a startling evolutionary diversity, with up to 5 independent origins of Vgsc-995 mutations found within just 8 haplotypes. Thus, despite having been first recorded over 10 years ago, Vgsc resistance mutations in Tanzanian An. arabiensis have remained at stable low frequencies. Overall, our results provide a new copy number marker for monitoring resistance to PM in malaria mosquitoes, and reveal the complex picture of resistance patterns in An. arabiensis.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 12","pages":"e3002898"},"PeriodicalIF":9.8,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11620391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142787435","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}