Jan de Witt, Tom Luthe, Johanna Wiechert, Kenneth Jensen, Tino Polen, Astrid Wirtz, Stephan Thies, Julia Frunzke, Benedikt Wynands, Nick Wierckx
{"title":"Upcycling of polyamides through chemical hydrolysis and engineered Pseudomonas putida","authors":"Jan de Witt, Tom Luthe, Johanna Wiechert, Kenneth Jensen, Tino Polen, Astrid Wirtz, Stephan Thies, Julia Frunzke, Benedikt Wynands, Nick Wierckx","doi":"10.1038/s41564-025-01929-5","DOIUrl":"https://doi.org/10.1038/s41564-025-01929-5","url":null,"abstract":"<p>Aliphatic polyamides, or nylons, are widely used in the textile and automotive industry due to their high durability and tensile strength, but recycling rates are below 5%. Chemical recycling of polyamides is possible but typically yields mixtures of monomers and oligomers which hinders downstream purification. Here, <i>Pseudomonas putida</i> KT2440 was engineered to metabolize C<sub>6</sub>-polyamide monomers such as 6-aminohexanoic acid, ε-caprolactam and 1,6-hexamethylenediamine, guided by adaptive laboratory evolution. Heterologous expression of nylonases also enabled <i>P. putida</i> to metabolize linear and cyclic nylon oligomers derived from chemical polyamide hydrolysis. RNA sequencing and reverse engineering revealed the metabolic pathways for these non-natural substrates. To demonstrate microbial upcycling, the <i>phaCAB</i> operon from <i>Cupriavidus necator</i> was heterologously expressed to enable production of polyhydroxybutyrate (PHB) from PA6 hydrolysates. This study presents a microbial host for the biological conversion, in combination with chemical hydrolysis, of polyamide monomers and mixed polyamids hydrolysates to a value-added product.</p>","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"85 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143375383","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":"Bacterial adhesion strategies and countermeasures in urinary tract infection","authors":"Carlos Flores, Jennifer L. Rohn","doi":"10.1038/s41564-025-01926-8","DOIUrl":"https://doi.org/10.1038/s41564-025-01926-8","url":null,"abstract":"<p>Urinary tract infections (UTIs) are compounded by antimicrobial resistance, which increases the risk of UTI recurrence and antibiotic treatment failure. This also intensifies the burden of disease upon healthcare systems worldwide, and of morbidity and mortality. Uropathogen adhesion is a critical step in the pathogenic process, as has been mainly shown for <i>Escherichia coli</i>, <i>Pseudomonas aeruginosa</i>, <i>Klebsiella pneumoniae</i>, <i>Streptococcus agalactiae</i>, <i>Proteus</i>, <i>Enterococcus</i> and <i>Staphylococcus</i> species. Although many bacterial adhesion molecules from these uropathogens have been described, our understanding of their contributions to UTIs is limited. Here we explore knowledge gaps in the UTI field, as we discuss the broader repertoire of uropathogen adhesins, including their role beyond initial attachment and the counter-responses of the host immune system. Finally, we describe the development of therapeutic approaches that target uropathogenic adhesion strategies and provide potential alternatives to antibiotics.</p>","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"144 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143375382","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}
Edward A. Partlow, Anna Jaeggi-Wong, Steven D. Planitzer, Nick Berg, Zhenyu Li, Tijana Ivanovic
{"title":"Influenza A virus rapidly adapts particle shape to environmental pressures","authors":"Edward A. Partlow, Anna Jaeggi-Wong, Steven D. Planitzer, Nick Berg, Zhenyu Li, Tijana Ivanovic","doi":"10.1038/s41564-025-01925-9","DOIUrl":"https://doi.org/10.1038/s41564-025-01925-9","url":null,"abstract":"<p>Enveloped viruses such as influenza A virus (IAV) often produce a mixture of virion shapes, ranging from 100 nm spheres to micron-long filaments. Spherical virions use fewer resources, while filamentous virions resist cell-entry pressures such as antibodies. While shape changes are believed to require genetic adaptation, the mechanisms of how viral mutations alter shape remain unclear. Here we find that IAV dynamically adjusts its shape distribution in response to environmental pressures. We developed a quantitative flow virometry assay to measure the shape of viral particles under various infection conditions (such as multiplicity, replication inhibition and antibody treatment) while using different combinations of IAV strains and cell lines. We show that IAV rapidly tunes its shape distribution towards spheres under optimal conditions but favours filaments under attenuation. Our work demonstrates that this phenotypic flexibility allows IAV to rapidly respond to environmental pressures in a way that provides dynamic adaptation potential in changing surroundings.</p>","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"44 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143375381","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}
Puspendu Sardar, Benjamin S. Beresford-Jones, Wangmingyu Xia, Omar Shabana, Satoshi Suyama, Ruben J. F. Ramos, Amelia T. Soderholm, Panagiotis Tourlomousis, Paula Kuo, Alexander C. Evans, Charlotte J. Imianowski, Alberto G. Conti, Alexander J. Wesolowski, Natalie M. Baker, Emily A. L. McCord, Klaus Okkenhaug, Sarah K. Whiteside, Rahul Roychoudhuri, Clare E. Bryant, Justin R. Cross, Virginia A. Pedicord
{"title":"Gut microbiota-derived hexa-acylated lipopolysaccharides enhance cancer immunotherapy responses","authors":"Puspendu Sardar, Benjamin S. Beresford-Jones, Wangmingyu Xia, Omar Shabana, Satoshi Suyama, Ruben J. F. Ramos, Amelia T. Soderholm, Panagiotis Tourlomousis, Paula Kuo, Alexander C. Evans, Charlotte J. Imianowski, Alberto G. Conti, Alexander J. Wesolowski, Natalie M. Baker, Emily A. L. McCord, Klaus Okkenhaug, Sarah K. Whiteside, Rahul Roychoudhuri, Clare E. Bryant, Justin R. Cross, Virginia A. Pedicord","doi":"10.1038/s41564-025-01930-y","DOIUrl":"https://doi.org/10.1038/s41564-025-01930-y","url":null,"abstract":"<p>The gut microbiome modulates immunotherapy treatment responses, and this may explain why immune checkpoint inhibitors, such as anti-PD-1, are only effective in some patients. Previous studies correlated lipopolysaccharide (LPS)-producing gut microbes with poorer prognosis; however, LPS from diverse bacterial species can range from immunostimulatory to inhibitory. Here, by functionally analysing faecal metagenomes from 112 patients with melanoma, we found that a subset of LPS-producing bacteria encoding immunostimulatory hexa-acylated LPS was enriched in microbiomes of clinical responders. In an implanted tumour mouse model of anti-PD-1 treatment, microbiota-derived hexa-acylated LPS was required for effective anti-tumour immune responses, and LPS-binding antibiotics and a small-molecule TLR4 antagonist abolished anti-PD-1 efficacy. Conversely, oral administration of hexa-acylated LPS to mice significantly augmented anti-PD-1-mediated anti-tumour immunity. Penta-acylated LPS did not improve anti-PD-1 efficacy in vivo and inhibited hexa-acylated LPS-induced immune activation in vitro. Microbiome hexa-acylated LPS therefore represents an accessible predictor and potential enhancer of immunotherapy responses.</p>","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"13 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143375418","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}
Yonatan Chemla, Connor J. Sweeney, Christopher A. Wozniak, Christopher A. Voigt
{"title":"Design and regulation of engineered bacteria for environmental release","authors":"Yonatan Chemla, Connor J. Sweeney, Christopher A. Wozniak, Christopher A. Voigt","doi":"10.1038/s41564-024-01918-0","DOIUrl":"10.1038/s41564-024-01918-0","url":null,"abstract":"Emerging products of biotechnology involve the release of living genetically modified microbes (GMMs) into the environment. However, regulatory challenges limit their use. So far, GMMs have mainly been tested in agriculture and environmental cleanup, with few approved for commercial purposes. Current government regulations do not sufficiently address modern genetic engineering and limit the potential of new applications, including living therapeutics, engineered living materials, self-healing infrastructure, anticorrosion coatings and consumer products. Here, based on 47 global studies on soil-released GMMs and laboratory microcosm experiments, we discuss the environmental behaviour of released bacteria and offer engineering strategies to help improve performance, control persistence and reduce risk. Furthermore, advanced technologies that improve GMM function and control, but lead to increases in regulatory scrutiny, are reviewed. Finally, we propose a new regulatory framework informed by recent data to maximize the benefits of GMMs and address risks. Chemla et al. review the release of bacteria into the environment and propose engineering strategies to help improve performance and reduce risk.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 2","pages":"281-300"},"PeriodicalIF":20.5,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143084096","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":"Ensuring rigour of low-biomass microbiome research","authors":"","doi":"10.1038/s41564-025-01939-3","DOIUrl":"10.1038/s41564-025-01939-3","url":null,"abstract":"Determining whether human organs house a resident microbiome is challenging and the findings can be controversial. However, forging collaborations and careful study design can help overcome these issues.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 2","pages":"261-262"},"PeriodicalIF":20.5,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41564-025-01939-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143121525","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}
Dan Xu, Mengyao Guo, Xin Xu, Gan Luo, Yaxin Liu, Stephen J. Bush, Chengyao Wang, Tun Xu, Wenxin Zeng, Chongbing Liao, Qingxia Wang, Wei Zhao, Wenying Zhao, Yuezhuangnan Liu, Shanshan Li, Shuangshuang Zhao, Yaming Jiu, Nathalie Sauvonnet, Wuyuan Lu, Philippe J. Sansonetti, Kai Ye
{"title":"Shigella infection is facilitated by interaction of human enteric α-defensin 5 with colonic epithelial receptor P2Y11","authors":"Dan Xu, Mengyao Guo, Xin Xu, Gan Luo, Yaxin Liu, Stephen J. Bush, Chengyao Wang, Tun Xu, Wenxin Zeng, Chongbing Liao, Qingxia Wang, Wei Zhao, Wenying Zhao, Yuezhuangnan Liu, Shanshan Li, Shuangshuang Zhao, Yaming Jiu, Nathalie Sauvonnet, Wuyuan Lu, Philippe J. Sansonetti, Kai Ye","doi":"10.1038/s41564-024-01901-9","DOIUrl":"10.1038/s41564-024-01901-9","url":null,"abstract":"Human enteric α-defensin 5 (HD5) is an immune system peptide that acts as an important antimicrobial factor but is also known to promote pathogen infections by enhancing adhesion of the pathogens. The mechanistic basis of these conflicting functions is unknown. Here we show that HD5 induces abundant filopodial extensions in epithelial cells that capture Shigella, a major human enteroinvasive pathogen that is able to exploit these filopodia for invasion, revealing a mechanism for HD5-augmented bacterial invasion. Using multi-omics screening and in vitro, organoid, dynamic gut-on-chip and in vivo models, we identify the HD5 receptor as P2Y11, a purinergic receptor distributed apically on the luminal surface of the human colonic epithelium. Inhibitor screening identified cAMP-PKA signalling as the main pathway mediating the cytoskeleton-regulating activity of HD5. In illuminating this mechanism of Shigella invasion, our findings raise the possibility of alternative intervention strategies against HD5-augmented infections. HD5 induces filopodial extensions in epithelial cells that the pathogen Shigella exploits to facilitate invasion and infection.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 2","pages":"509-526"},"PeriodicalIF":20.5,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143077191","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}
Miles Richardson, Shijie Zhao, Liyuan Lin, Ravi U. Sheth, Yiming Qu, Jeongchan Lee, Thomas Moody, Deirdre Ricaurte, Yiming Huang, Florencia Velez-Cortes, Guillaume Urtecho, Harris H. Wang
{"title":"SAMPL-seq reveals micron-scale spatial hubs in the human gut microbiome","authors":"Miles Richardson, Shijie Zhao, Liyuan Lin, Ravi U. Sheth, Yiming Qu, Jeongchan Lee, Thomas Moody, Deirdre Ricaurte, Yiming Huang, Florencia Velez-Cortes, Guillaume Urtecho, Harris H. Wang","doi":"10.1038/s41564-024-01914-4","DOIUrl":"10.1038/s41564-024-01914-4","url":null,"abstract":"The local arrangement of microbes can profoundly impact community assembly, function and stability. However, our understanding of the spatial organization of the human gut microbiome at the micron scale is limited. Here we describe a high-throughput and streamlined method called Split-And-pool Metagenomic Plot-sampling sequencing (SAMPL-seq) to capture spatial co-localization in a complex microbial consortium. The method obtains microbial composition of micron-scale subcommunities through split-and-pool barcoding. SAMPL-seq analysis of the healthy human gut microbiome identified bacterial taxa pairs that consistently co-occurred both over time and across multiple individuals. These co-localized microbes organize into spatially distinct groups or ‘spatial hubs’ dominated by Bacteroidaceae, Ruminococcaceae and Lachnospiraceae families. Using inulin as a dietary perturbation, we observed reversible spatial rearrangement of the gut microbiome where specific taxa form new local partnerships. Spatial metagenomics using SAMPL-seq can unlock insights into microbiomes at the micron scale. Split-And-pool Metagenomic Plot-sampling sequencing (SAMPL-seq) can be applied to complex microbial communities to reveal spatial co-localization of microbes at the micron scale.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 2","pages":"527-540"},"PeriodicalIF":20.5,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143077192","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":"Sliding clamp protein enables long-range gene silencing in a bacterial plasmid","authors":"","doi":"10.1038/s41564-025-01924-w","DOIUrl":"10.1038/s41564-025-01924-w","url":null,"abstract":"Long-distance gene regulation is uncommon in bacteria, and its molecular mechanisms are unclear. Using a combination of structural, biochemical and single-molecule techniques, researchers revealed that KorB, a DNA-sliding clamp capable of traversing long genomic distances, is captured by KorA to form a stable transcriptional co-repressor complex on a bacterial plasmid.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 2","pages":"279-280"},"PeriodicalIF":20.5,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143077203","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}
Gigliola Zanghí, Hardik Patel, Jenny L. Smith, Nelly Camargo, Yeji Bae, Eva Hesping, Justin A. Boddey, Kannan Venugopal, Matthias Marti, Erika L. Flannery, Vorada Chuenchob, Matthew E. Fishbaugher, Sebastian A. Mikolajczak, Wanlapa Roobsoong, Jetsumon Sattabongkot, Priya Gupta, Lucia Pazzagli, Nastaran Rezakhani, William Betz, Kiera Hayes, Debashree Goswami, Ashley M. Vaughan, Stefan H. I. Kappe
{"title":"Genome-wide gene expression profiles throughout human malaria parasite liver stage development in humanized mice","authors":"Gigliola Zanghí, Hardik Patel, Jenny L. Smith, Nelly Camargo, Yeji Bae, Eva Hesping, Justin A. Boddey, Kannan Venugopal, Matthias Marti, Erika L. Flannery, Vorada Chuenchob, Matthew E. Fishbaugher, Sebastian A. Mikolajczak, Wanlapa Roobsoong, Jetsumon Sattabongkot, Priya Gupta, Lucia Pazzagli, Nastaran Rezakhani, William Betz, Kiera Hayes, Debashree Goswami, Ashley M. Vaughan, Stefan H. I. Kappe","doi":"10.1038/s41564-024-01905-5","DOIUrl":"10.1038/s41564-024-01905-5","url":null,"abstract":"Gene expression of Plasmodium falciparum (Pf) liver-stage (LS) parasites has remained poorly characterized, although they are major vaccine and drug targets. Using a human liver-chimaeric mouse model and a fluorescent parasite line (PfNF54CSPGFP), we isolated PfLS and performed transcriptomics on key LS developmental phases. We linked clustered gene expression to ApiAP2, a major family of transcription factors that regulate the parasite life cycle. This provided insights into transcriptional regulation of LS infection and expression of essential LS metabolic and biosynthetic pathways. We observed expression of antigenically variant PfEMP1 proteins and the major Pf protein export machine PTEX and identified protein candidates that might be exported by LS parasites. Comparing Pf and P. vivax LS transcriptomes, we uncovered differences in their expression of sexual commitment factors. This data will aid LS research and vaccine and drug target identification for prevention of malaria infection. Transcriptomics of gene expression in Plasmodium falciparum liver-stage parasites reveals transcriptional regulation, metabolic pathways and antigen expression, facilitating vaccine and drug target identification.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 2","pages":"569-584"},"PeriodicalIF":20.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41564-024-01905-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143071898","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}