{"title":"HIV-1 capsid found guilty of breaking and entering","authors":"Adarsh Dharan, Edward M. Campbell","doi":"10.1038/s41564-025-02071-y","DOIUrl":"https://doi.org/10.1038/s41564-025-02071-y","url":null,"abstract":"Two new studies find that HIV-1 can enter the nucleus by cracking or distorting nuclear pore structures, explaining how the HIV-1 capsid can seemingly ignore the size limitations associated with conventional nuclear import.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"31 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144747386","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}
Yong Fan, Liwei Lyu, Ruben Vazquez-Uribe, Wanliang Zhang, Mareike Bongers, Andreas Koulouktsis, Mengliu Yang, Vita Sereika-Bejder, Tulika Arora, Evelina Stankevic, Jeremy Armetta, Franziska Zosel, Charlotta D. de la Cour, Lotte Simonsen, Alina Kulakova, Michael Wierer, Pernille Harris, Joachim Gæde, Peter Rossing, Filip K. Knop, Tune H. Pers, Tue Haldor Hansen, Trine Nielsen, Ling Li, Kristian Strømgaard, Gangyi Yang, Morten Otto Alexander Sommer, Oluf Pedersen
{"title":"Polypeptides synthesized by common bacteria in the human gut improve rodent metabolism","authors":"Yong Fan, Liwei Lyu, Ruben Vazquez-Uribe, Wanliang Zhang, Mareike Bongers, Andreas Koulouktsis, Mengliu Yang, Vita Sereika-Bejder, Tulika Arora, Evelina Stankevic, Jeremy Armetta, Franziska Zosel, Charlotta D. de la Cour, Lotte Simonsen, Alina Kulakova, Michael Wierer, Pernille Harris, Joachim Gæde, Peter Rossing, Filip K. Knop, Tune H. Pers, Tue Haldor Hansen, Trine Nielsen, Ling Li, Kristian Strømgaard, Gangyi Yang, Morten Otto Alexander Sommer, Oluf Pedersen","doi":"10.1038/s41564-025-02064-x","DOIUrl":"https://doi.org/10.1038/s41564-025-02064-x","url":null,"abstract":"<p>The human gut microbiota has the potential to synthesize proteins that may influence host metabolism. Here we report two polypeptides, RUMTOR-derived peptide (RORDEP) 1 and RORDEP2, circulating in human blood and synthesized by specific strains of gut commensal <i>Ruminococcus torques</i> that correlate inversely with adiposity in humans. Oral gavage with RORDEP-expressing strains improved glucose tolerance, increased bone density and reduced fat mass with an enhanced expression of genes and proteins involved in thermogenesis and lipolysis in lean mice on a high-fat diet and diet-induced obese mice. Recombinant RORDEP1 given to rats intraperitoneally decreased plasma gastric inhibitory polypeptide but increased glucagon-like peptide 1, peptide YY and insulin. Intestinal delivery of recombinant RORDEP1 to rats potentiated insulin-mediated inhibition of hepatic glucose production by downregulating genes and proteins controlling liver gluconeogenesis, glycogenolysis and lipogenesis but upregulating those involved in insulin signalling, glycogenesis and glycolysis. These preclinical findings warrant the exploration of RORDEPs for the prevention and treatment of human metabolic disorders.</p>","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"13 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144747387","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":"From farm to factory to fork","authors":"Kate S. Baker, Alison E. Mather","doi":"10.1038/s41564-025-02069-6","DOIUrl":"https://doi.org/10.1038/s41564-025-02069-6","url":null,"abstract":"A recent study has examined the flow of antimicrobial resistance genes in food production using nearly 2,000 metagenomes, indicating a potential role for contamination in processing facilities.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"1 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144747385","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":"Deep, long-read metagenome sequencing expands knowledge of prokaryotic phylogenetic diversity","authors":"","doi":"10.1038/s41564-025-02073-w","DOIUrl":"https://doi.org/10.1038/s41564-025-02073-w","url":null,"abstract":"Deep, long-read metagenome sequencing of 154 soil and sediment samples from diverse habitats in Denmark enabled recovery of 4,894 high-quality and highly contiguous microbial genomes. The vast untapped microbial diversity in complex ecosystems can now be systematically explored, categorized and capitalized on.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"14 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144747586","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}
Narciso M. Quijada, José F. Cobo-Díaz, Vincenzo Valentino, Coral Barcenilla, Francesca De Filippis, Raul Cabrera-Rubio, Niccolò Carlino, Federica Pinto, Monika Dzieciol, Inés Calvete-Torre, Carlos Sabater, Francesco Rubino, Stephen Knobloch, Sigurlaug Skirnisdottir, Lorena Ruiz, Mercedes López, Miguel Prieto, Viggó Thór Marteinsson, Abelardo Margolles, Nicola Segata, Paul D. Cotter, Martin Wagner, Danilo Ercolini, Avelino Alvarez-Ordóñez
{"title":"The food-associated resistome is shaped by processing and production environments","authors":"Narciso M. Quijada, José F. Cobo-Díaz, Vincenzo Valentino, Coral Barcenilla, Francesca De Filippis, Raul Cabrera-Rubio, Niccolò Carlino, Federica Pinto, Monika Dzieciol, Inés Calvete-Torre, Carlos Sabater, Francesco Rubino, Stephen Knobloch, Sigurlaug Skirnisdottir, Lorena Ruiz, Mercedes López, Miguel Prieto, Viggó Thór Marteinsson, Abelardo Margolles, Nicola Segata, Paul D. Cotter, Martin Wagner, Danilo Ercolini, Avelino Alvarez-Ordóñez","doi":"10.1038/s41564-025-02059-8","DOIUrl":"https://doi.org/10.1038/s41564-025-02059-8","url":null,"abstract":"<p>Food production systems may act as transmission routes for antimicrobial-resistant (AMR) bacteria and AMR genes (AMRGs) to humans. However, the food resistome remains poorly characterized. Here 1,780 raw-material (milk, brine, fresh meat and so on), end-product (cheese, fish, meat products and vegetables) and surface (processing, cooling, smoking, ripening and packing rooms) samples from 113 food processing facilities were subjected to whole-metagenome sequencing. Assembly-free analyses demonstrated that >70% of all known AMRGs, including many predicted to confer resistance to critically important antibiotics, circulate throughout food production chains, with those conferring resistance to tetracyclines, β-lactams, aminoglycosides and macrolides being the most abundant overall. An assembly-based analysis highlighted that bacteria from the ESKAPEE group, together with <i>Staphylococcus equorum</i> and <i>Acinetobacter johnsonii</i>, were the main AMRG carriers. Further evaluation demonstrated that ~40% of the AMRGs were associated with mobile genetic elements, mainly plasmids. These findings will help guide the appropriate use of biocides and other antimicrobials in food production settings when designing efficient antimicrobial stewardship policies.</p>","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"12 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144737012","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}
Virginie Girault, Alexey Stukalov, Madalina Elena Carter-Timofte, Jonny Hertzog, Melissa Verin, Katharina Austen, Darya A. Haas, Lila Oubraham, Antonio Piras, Susanne Maidl, Rupert Öllinger, Roland Rad, Ulrike Protzer, Benedikt B. Kaufer, Robert J. Lebbink, Jan Rehwinkel, Trine H. Mogensen, Andreas Pichlmair
{"title":"Multi-proteomic profiling of the varicella-zoster virus–host interface reveals host susceptibilities to severe infection","authors":"Virginie Girault, Alexey Stukalov, Madalina Elena Carter-Timofte, Jonny Hertzog, Melissa Verin, Katharina Austen, Darya A. Haas, Lila Oubraham, Antonio Piras, Susanne Maidl, Rupert Öllinger, Roland Rad, Ulrike Protzer, Benedikt B. Kaufer, Robert J. Lebbink, Jan Rehwinkel, Trine H. Mogensen, Andreas Pichlmair","doi":"10.1038/s41564-025-02068-7","DOIUrl":"https://doi.org/10.1038/s41564-025-02068-7","url":null,"abstract":"<p>Varicella-zoster virus (VZV) infects most humans and causes chickenpox, shingles and central nervous system pathologies. The molecular basis for these phenotypes remains elusive. Here we conducted a multi-proteomic survey on 64 individual VZV proteins and infection-induced perturbations in a neuronal cell line, identifying 900 interactors and 3,618 regulated host proteins. Data integration suggested molecular functions of viral proteins, such as a mechanism for the ORF61-mediated IFI16 degradation via the recruitment of E3 ligase co-factors. Moreover, we identified proviral host factors (MPP8 and ZNF280D) as potential targets to limit infection. Integration of exome sequencing analysis from patients with VZV-associated central nervous system pathologies identified nephrocystin 4 as a viral restriction factor, and its S862N variant, which showed reduced activity and decreased binding to the regulatory proteins 14-3-3. Collectively, our study provides a comprehensive herpesvirus–host interface resource, which aids our understanding of disease-associated molecular perturbations and data-driven identification of antiviral treatment options.</p>","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"26 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144737011","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}
Michaël Deghelt, Seung-Hyun Cho, Jiawei Sun, Sander K. Govers, Arne Janssens, Alix Vincent Dachsbeck, Han K. Remaut, Kerwyn Casey Huang, Jean-François Collet
{"title":"Peptidoglycan–outer membrane attachment generates periplasmic pressure to prevent lysis in Gram-negative bacteria","authors":"Michaël Deghelt, Seung-Hyun Cho, Jiawei Sun, Sander K. Govers, Arne Janssens, Alix Vincent Dachsbeck, Han K. Remaut, Kerwyn Casey Huang, Jean-François Collet","doi":"10.1038/s41564-025-02058-9","DOIUrl":"https://doi.org/10.1038/s41564-025-02058-9","url":null,"abstract":"<p>Bacteria are subject to a substantial concentration differential of osmolytes between the interior and exterior of the cell, resulting in turgor pressure. Failure to mechanically balance this turgor pressure causes cells to burst. Here, using microfluidics, imaging, biochemistry and mathematical modelling, we analysed how <i>Escherichia coli</i> cells with structural mutations in the envelope respond to hypoosmotic shocks. We show that the peptidoglycan cell wall forms a mechanical unit with the outer membrane that limits periplasmic volume increase under hypoosmotic shock, allowing osmotic pressure build-up in the periplasm. In turn, this periplasmic pressure balances cytoplasmic turgor across the inner membrane, preventing cell lysis and death. Thus, while the peptidoglycan layer is necessary, it is not sufficient to maintain turgor and protect cells from lysis. We propose a model in which the entire cell envelope, including the periplasm, collectively enables Gram-negative bacteria to overcome osmotic challenges.</p>","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"23 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144719702","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}
Ilke Aernout, Rein Verbeke, Fabien Thery, Patrick Willems, Uri Elia, Stefaan C. De Smedt, Rino Rappuoli, Dan Peer, Francis Impens, Ine Lentacker
{"title":"Challenges and opportunities in mRNA vaccine development against bacteria","authors":"Ilke Aernout, Rein Verbeke, Fabien Thery, Patrick Willems, Uri Elia, Stefaan C. De Smedt, Rino Rappuoli, Dan Peer, Francis Impens, Ine Lentacker","doi":"10.1038/s41564-025-02070-z","DOIUrl":"https://doi.org/10.1038/s41564-025-02070-z","url":null,"abstract":"<p>The global surge in antimicrobial resistance presents a critical threat to public health, emphasizing the urgent need for the development of new and more effective bacterial vaccines. Since the success of mRNA vaccines during the COVID-19 pandemic, this vaccine strategy has rapidly advanced, with most efforts focused on cancer immunotherapy and targeting viral pathogens. Recently, mRNA vaccines have entered the early phases of clinical development for bacterial diseases. However, bacteria present greater biological complexity compared with viruses, posing additional challenges for vaccine design, such as antigen selection, immune response and mRNA construct design. Here, we discuss critical aspects in the development of bacterial mRNA vaccines, from antigen selection to construct design. We also highlight the current preclinical landscape and discuss remaining translational challenges and future potential for mRNA vaccines against bacterial infections.</p>","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"60 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144719703","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":"Evolution of antifungal resistance in the environment","authors":"Norman van Rhijn, Johanna Rhodes","doi":"10.1038/s41564-025-02055-y","DOIUrl":"https://doi.org/10.1038/s41564-025-02055-y","url":null,"abstract":"<p>The emergence of drug-resistant fungal infections in agriculture and healthcare settings has caused severe implications for food security, public health and natural environments. They pose a substantial hazard for at-risk patient populations who often acquire serious and sometimes life-threatening infections. With the increasing use of fungicides in the environment, acquisition of resistance to fungicides and antifungal drugs pose a risk to health. In this Review we summarize the evolution, emergence and expansion of fungicide and antifungal drug resistance globally. We discuss different antifungals and fungicides, their modes of action and resistance mechanisms. Furthermore, we outline the current state of knowledge about the emergence and expansion of resistant fungi in hotspots and coldspots in the environment. Finally, we summarize alternative options and future directions in reducing antifungal resistance.</p>","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"129 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144719701","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":"Remote control designer probiotics","authors":"David Carreño, David T. Riglar","doi":"10.1038/s41564-025-02072-x","DOIUrl":"https://doi.org/10.1038/s41564-025-02072-x","url":null,"abstract":"Zhang and colleagues demonstrate the potential for disease monitoring and therapeutic delivery in the gut by interfacing engineered smart probiotics with a pill-camera-style endoscope.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"24 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144719482","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}