Pub Date : 2025-11-27DOI: 10.1038/s41564-025-02174-6
Darlan da Silva Candido, Simon Dellicour, Laura V. Cooper, Carlos A. Prete Jr, David Jorgensen, Christopher B. Uzzell, Arend Voorman, Hil Lyons, Dimitra Klapsa, Manasi Majumdar, Kafayat Arowolo, Corey M. Peak, Ananda S. Bandyopadhyay, Javier Martin, Nicholas C. Grassly, Isobel M. Blake
Outbreaks of vaccine-derived poliovirus type 2 (cVDPV2) have become a major threat to polio eradication. However, variations in spatiotemporal spread have not been quantified. Here we analysed cVDPV2 cases and wild poliovirus type 1 sequences to uncover spatiotemporal patterns and drivers of poliovirus spread. Between 1 May 2016 and 29 September 2023, 3,120 cVDPV2 poliomyelitis cases were reported across 75 outbreaks in 39 countries. Outbreaks had a median observed circulation of 202 (range 0–1,905) days and a median maximum distance of 231 (range 0–4,442) km. Wavefront velocity analysis of large outbreaks revealed a median velocity of spread of 2.3 (5th–95th percentile 0.7–9.2) km per day. International borders were associated with a slower velocity of spread (P < 0.001), in periods with high estimated population immunity. Phylogeographic analysis of 1,572 global wild poliovirus 1 sequences revealed that historic spread resembles recent cVDPV2 patterns and that international spread is largely sustained by unidirectional movement between neighbouring countries. Our findings offer insights for enhancing the geographical scope of vaccination response in the final phases of poliovirus eradication. Vaccine-derived poliovirus type 2 currently spreads similarly to historical poliovirus—unidirectionally across neighbouring countries at a median velocity of 2.3 km per day. International borders are associated with slower velocity when immunity is high.
{"title":"Historical and current spatiotemporal patterns of wild and vaccine-derived poliovirus spread","authors":"Darlan da Silva Candido, Simon Dellicour, Laura V. Cooper, Carlos A. Prete Jr, David Jorgensen, Christopher B. Uzzell, Arend Voorman, Hil Lyons, Dimitra Klapsa, Manasi Majumdar, Kafayat Arowolo, Corey M. Peak, Ananda S. Bandyopadhyay, Javier Martin, Nicholas C. Grassly, Isobel M. Blake","doi":"10.1038/s41564-025-02174-6","DOIUrl":"10.1038/s41564-025-02174-6","url":null,"abstract":"Outbreaks of vaccine-derived poliovirus type 2 (cVDPV2) have become a major threat to polio eradication. However, variations in spatiotemporal spread have not been quantified. Here we analysed cVDPV2 cases and wild poliovirus type 1 sequences to uncover spatiotemporal patterns and drivers of poliovirus spread. Between 1 May 2016 and 29 September 2023, 3,120 cVDPV2 poliomyelitis cases were reported across 75 outbreaks in 39 countries. Outbreaks had a median observed circulation of 202 (range 0–1,905) days and a median maximum distance of 231 (range 0–4,442) km. Wavefront velocity analysis of large outbreaks revealed a median velocity of spread of 2.3 (5th–95th percentile 0.7–9.2) km per day. International borders were associated with a slower velocity of spread (P < 0.001), in periods with high estimated population immunity. Phylogeographic analysis of 1,572 global wild poliovirus 1 sequences revealed that historic spread resembles recent cVDPV2 patterns and that international spread is largely sustained by unidirectional movement between neighbouring countries. Our findings offer insights for enhancing the geographical scope of vaccination response in the final phases of poliovirus eradication. Vaccine-derived poliovirus type 2 currently spreads similarly to historical poliovirus—unidirectionally across neighbouring countries at a median velocity of 2.3 km per day. International borders are associated with slower velocity when immunity is high.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 12","pages":"3148-3161"},"PeriodicalIF":19.4,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-025-02174-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145609468","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}
Pub Date : 2025-11-26DOI: 10.1038/s41564-025-02182-6
Indra Roux, Anna E. Lindell, Anne Grießhammer, Tom Smith, Shagun Krishna, Rui Guan, Deniz Rad, Luisa Faria, Sonja Blasche, Kaustubh R. Patil, Nicole C. Kleinstreuer, Lisa Maier, Stephan Kamrad, Kiran R. Patil
Industrial and agricultural chemicals such as pesticides are often considered to have restricted biological activity. Yet, there are concerns regarding their broader toxicity range and impact on human gut microbiota. Here we report a systematic in vitro screening to assess the impact of 1,076 pollutants, spanning diverse chemistries and indicated applications, on 22 prevalent gut bacteria. Our investigation uncovered 588 inhibitory interactions involving 168 chemicals, the majority of which were not previously reported to have antibacterial properties. Fungicides and industrial chemicals showed the largest impact, with around 30% exhibiting anti-gut-bacterial properties. We demonstrate that the scale of our dataset enables a machine learning approach for predicting the antibacterial activity of pesticides. Mechanistically, chemical–genetic screens using transposon mutant libraries of Parabacteroides merdae and Bacteroides thetaiotaomicron implicated genes involved in conserved efflux pathways, including the acrR locus, as mediators of pollutant resistance. We also found that loss-of-function mutations in genes coding for metabolic enzymes were selected under pollutant exposure, including those for branched short-chain fatty acid biosynthesis under tetrabromobisphenol A, a flame retardant. Taken together, our results suggest that the antibacterial activity of chemical pollutants should be considered in future studies on the microbiome and the emergence of antimicrobial resistance, as well as in toxicological assessments. Screening of 1,076 compounds reveals 168 chemical pollutants with inhibitory effects on gut bacteria and genetic screens indicate commonality between pollutant and antibiotic resistance.
{"title":"Industrial and agricultural chemicals exhibit antimicrobial activity against human gut bacteria in vitro","authors":"Indra Roux, Anna E. Lindell, Anne Grießhammer, Tom Smith, Shagun Krishna, Rui Guan, Deniz Rad, Luisa Faria, Sonja Blasche, Kaustubh R. Patil, Nicole C. Kleinstreuer, Lisa Maier, Stephan Kamrad, Kiran R. Patil","doi":"10.1038/s41564-025-02182-6","DOIUrl":"10.1038/s41564-025-02182-6","url":null,"abstract":"Industrial and agricultural chemicals such as pesticides are often considered to have restricted biological activity. Yet, there are concerns regarding their broader toxicity range and impact on human gut microbiota. Here we report a systematic in vitro screening to assess the impact of 1,076 pollutants, spanning diverse chemistries and indicated applications, on 22 prevalent gut bacteria. Our investigation uncovered 588 inhibitory interactions involving 168 chemicals, the majority of which were not previously reported to have antibacterial properties. Fungicides and industrial chemicals showed the largest impact, with around 30% exhibiting anti-gut-bacterial properties. We demonstrate that the scale of our dataset enables a machine learning approach for predicting the antibacterial activity of pesticides. Mechanistically, chemical–genetic screens using transposon mutant libraries of Parabacteroides merdae and Bacteroides thetaiotaomicron implicated genes involved in conserved efflux pathways, including the acrR locus, as mediators of pollutant resistance. We also found that loss-of-function mutations in genes coding for metabolic enzymes were selected under pollutant exposure, including those for branched short-chain fatty acid biosynthesis under tetrabromobisphenol A, a flame retardant. Taken together, our results suggest that the antibacterial activity of chemical pollutants should be considered in future studies on the microbiome and the emergence of antimicrobial resistance, as well as in toxicological assessments. Screening of 1,076 compounds reveals 168 chemical pollutants with inhibitory effects on gut bacteria and genetic screens indicate commonality between pollutant and antibiotic resistance.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 12","pages":"3107-3121"},"PeriodicalIF":19.4,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-025-02182-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145599904","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}
Pub Date : 2025-11-25DOI: 10.1038/s41564-025-02193-3
Chahat Mehra, Jesús Alvarado Valverde, Ana Margarida Nogueira Matias, Francesca Torelli, Tânia Catarina Medeiros, Julian Straub, James D. Asaki, Peter J. Bradley, Katja Luck, Steffen Lawo, Moritz Treeck, Lena Pernas
Membrane contact sites (MCS) are essential for organelle communication in eukaryotic cells. Pathogens also establish MCS with host organelles, but the mechanisms underlying these interactions and their role in infection remain poorly understood. Here, using a fluorescence sensor and CRISPR-based loss-of-function screening, together with imaging and proteomics, we identify the parasite effector mediating MCS between host endoplasmic reticulum (ER) and the vacuole containing the intracellular parasite Toxoplasma gondii. TgROP1 acts as a tether and mimics a canonical FFAT motif to bind the host ER proteins VAPA and VAPB. The loss of VAPA/B abolished host ER–Toxoplasma MCS and decreased pathogen growth. These findings indicate that targeting of host MCS tethers is a strategy exploited by pathogens during infection, which could inform future treatment design. The Toxoplasma gondii effector TgROP1 mimics host factors to bind VAPA/B, thereby establishing parasite–host ER contact sites.
{"title":"Toxoplasma effector TgROP1 establishes membrane contact sites with the endoplasmic reticulum during infection","authors":"Chahat Mehra, Jesús Alvarado Valverde, Ana Margarida Nogueira Matias, Francesca Torelli, Tânia Catarina Medeiros, Julian Straub, James D. Asaki, Peter J. Bradley, Katja Luck, Steffen Lawo, Moritz Treeck, Lena Pernas","doi":"10.1038/s41564-025-02193-3","DOIUrl":"10.1038/s41564-025-02193-3","url":null,"abstract":"Membrane contact sites (MCS) are essential for organelle communication in eukaryotic cells. Pathogens also establish MCS with host organelles, but the mechanisms underlying these interactions and their role in infection remain poorly understood. Here, using a fluorescence sensor and CRISPR-based loss-of-function screening, together with imaging and proteomics, we identify the parasite effector mediating MCS between host endoplasmic reticulum (ER) and the vacuole containing the intracellular parasite Toxoplasma gondii. TgROP1 acts as a tether and mimics a canonical FFAT motif to bind the host ER proteins VAPA and VAPB. The loss of VAPA/B abolished host ER–Toxoplasma MCS and decreased pathogen growth. These findings indicate that targeting of host MCS tethers is a strategy exploited by pathogens during infection, which could inform future treatment design. The Toxoplasma gondii effector TgROP1 mimics host factors to bind VAPA/B, thereby establishing parasite–host ER contact sites.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 12","pages":"3331-3345"},"PeriodicalIF":19.4,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-025-02193-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145594091","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}
Pub Date : 2025-11-24DOI: 10.1038/s41564-025-02175-5
Santiago E. Caño Muñiz, Stephen Trigg, Georgeos Hardo, Anja Hagting, Ieuan E. Evans, Christopher Ruis, Ali F. Alsulami, David Summers, Felicity Crawshay-Williams, Tom L. Blundell, Lucas Boeck, Somenath Bakshi, R. Andres Floto
Porins mediate the passage of hydrophilic nutrients and antibiotics across the outer membrane but might contribute to proton leak from the periplasm, suggesting that their conductance could be regulated. Here we show, using single-cell imaging, that porin permeability in Escherichia coli is controlled by changes in periplasmic H+ and K+ concentration. Conductance through porins increases with low periplasmic H+ caused by starvation, promoting nutrient uptake, and decreases with periplasmic acidification during growth in lipid media, limiting proton loss. High metabolic activity during growth in glucose media, however, activates the inner membrane voltage-gated potassium channel, Kch, increasing periplasmic potassium and enhancing porin permeability to dissipate reactive oxygen species. This metabolic control of porin permeability explains the observed increase in ciprofloxacin resistance of bacteria catabolizing lipids and clarifies the impact of mutations in central metabolism genes on drug resistance, identifying Kch as a therapeutic target to improve bacterial killing by antibiotics. The permeability of bacterial porins is dynamically regulated by periplasmic proton and potassium concentrations, altering antibiotic resistance.
{"title":"Metabolic control of porin permeability influences antibiotic resistance in Escherichia coli","authors":"Santiago E. Caño Muñiz, Stephen Trigg, Georgeos Hardo, Anja Hagting, Ieuan E. Evans, Christopher Ruis, Ali F. Alsulami, David Summers, Felicity Crawshay-Williams, Tom L. Blundell, Lucas Boeck, Somenath Bakshi, R. Andres Floto","doi":"10.1038/s41564-025-02175-5","DOIUrl":"10.1038/s41564-025-02175-5","url":null,"abstract":"Porins mediate the passage of hydrophilic nutrients and antibiotics across the outer membrane but might contribute to proton leak from the periplasm, suggesting that their conductance could be regulated. Here we show, using single-cell imaging, that porin permeability in Escherichia coli is controlled by changes in periplasmic H+ and K+ concentration. Conductance through porins increases with low periplasmic H+ caused by starvation, promoting nutrient uptake, and decreases with periplasmic acidification during growth in lipid media, limiting proton loss. High metabolic activity during growth in glucose media, however, activates the inner membrane voltage-gated potassium channel, Kch, increasing periplasmic potassium and enhancing porin permeability to dissipate reactive oxygen species. This metabolic control of porin permeability explains the observed increase in ciprofloxacin resistance of bacteria catabolizing lipids and clarifies the impact of mutations in central metabolism genes on drug resistance, identifying Kch as a therapeutic target to improve bacterial killing by antibiotics. The permeability of bacterial porins is dynamically regulated by periplasmic proton and potassium concentrations, altering antibiotic resistance.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 12","pages":"3202-3214"},"PeriodicalIF":19.4,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-025-02175-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145582943","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}
Probiotics are promising alternatives to antibiotics for the treatment of intestinal infections, but the effects of probiotics alone are often insufficient. Here we uncovered synergism between antibacterial iron–sulfur nanozymes (nFeS) and tryptophan derivatives that protects mice and pigs against bacterial gut infections. nFeS selectively inhibited potential intestinal pathogens while sparing commensal Lactobacillus vaginalis, whose presence enhanced the protective activity of nFeS against Salmonella enterica subsp. enterica serovar Typhimurium in vivo. Metabolomics and mutational analysis revealed that L. vaginalis synthesized 2-indolecarboxylic acid from a tryptophan derivative, indole-3-carboxaldehyde, a reaction that was catalysed by nFeS. The cytoplasmic pH of L. vaginalis (pH 7.5) allowed 2-indolecarboxylic acid to chelate free ferrous ions released by nFeS, thereby protecting it from antibacterial effects, whereas pathogens such as S. Typhimurium with a lower cytoplasmic pH were susceptible (pH 6.5). Pretreatment of pigs and mice with L. vaginalis and nFeS protected them against Salmonella infection. Our findings provide a foundation for improving probiotic bacteria-based therapies against intestinal infections. Iron‒sulfur nanozymes catalyse the production of an indole derivative, 2-indolecarboxylic acid, in Lactobacillus vaginalis, leading to a synergistic antibacterial activity that protects mice and weaned pigs against Salmonella Typhimurium infection.
{"title":"Nanozymes modulate probiotic tryptophan metabolism to prevent Salmonella infection in mammalian models","authors":"Zishen Lin, Yue Feng, Lei Chen, Jinping Wang, Qian Wang, Haolin Cao, Yang Gao, Lixue Wang, Ying Zhang, Jing Jiang, Lizeng Gao, Bing Dong","doi":"10.1038/s41564-025-02176-4","DOIUrl":"10.1038/s41564-025-02176-4","url":null,"abstract":"Probiotics are promising alternatives to antibiotics for the treatment of intestinal infections, but the effects of probiotics alone are often insufficient. Here we uncovered synergism between antibacterial iron–sulfur nanozymes (nFeS) and tryptophan derivatives that protects mice and pigs against bacterial gut infections. nFeS selectively inhibited potential intestinal pathogens while sparing commensal Lactobacillus vaginalis, whose presence enhanced the protective activity of nFeS against Salmonella enterica subsp. enterica serovar Typhimurium in vivo. Metabolomics and mutational analysis revealed that L. vaginalis synthesized 2-indolecarboxylic acid from a tryptophan derivative, indole-3-carboxaldehyde, a reaction that was catalysed by nFeS. The cytoplasmic pH of L. vaginalis (pH 7.5) allowed 2-indolecarboxylic acid to chelate free ferrous ions released by nFeS, thereby protecting it from antibacterial effects, whereas pathogens such as S. Typhimurium with a lower cytoplasmic pH were susceptible (pH 6.5). Pretreatment of pigs and mice with L. vaginalis and nFeS protected them against Salmonella infection. Our findings provide a foundation for improving probiotic bacteria-based therapies against intestinal infections. Iron‒sulfur nanozymes catalyse the production of an indole derivative, 2-indolecarboxylic acid, in Lactobacillus vaginalis, leading to a synergistic antibacterial activity that protects mice and weaned pigs against Salmonella Typhimurium infection.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 12","pages":"3272-3289"},"PeriodicalIF":19.4,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145582942","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}
Pub Date : 2025-11-21DOI: 10.1038/s41564-025-02187-1
Daniel S. C. Butler, Blanda Di Luccia, José G. Vilches-Moure, Denise M. Monack
Salmonella enterica can persist asymptomatically within tissues for extended periods. This is achieved through intricate host–pathogen interactions in immune cell aggregates called granulomas, wherein Salmonella establish favourable cellular niches to exploit while the host limits its expansion and tissue dissemination. Here, using a mouse model of persistent Salmonella infection, we identify a host-protective role for eosinophils in the control of Salmonella Typhimurium (STm) infection within the mesenteric lymph nodes, the main lymphoid tissue of STm persistence. Combining spatial transcriptomics and experimental manipulations, we found that monocytes and macrophages responding to STm infection recruited eosinophils in a C-C motif chemokine ligand 11 (CCL11)-dependent manner and enhanced their activation. The protein major basic protein, primarily expressed by eosinophils, was associated with altered macrophage polarization and bacterial control. Thus, eosinophils play a vital role in restraining Salmonella exploitation of granuloma macrophages at a key site of bacterial persistence. Eosinophils enhance granuloma-mediated control of persistent Salmonella infection in mice through CCL11-driven recruitment and MBP-dependent modulation of macrophage polarization and bacterial clearance.
{"title":"Eosinophils enhance granuloma-mediated control of persistent Salmonella infection in mice","authors":"Daniel S. C. Butler, Blanda Di Luccia, José G. Vilches-Moure, Denise M. Monack","doi":"10.1038/s41564-025-02187-1","DOIUrl":"10.1038/s41564-025-02187-1","url":null,"abstract":"Salmonella enterica can persist asymptomatically within tissues for extended periods. This is achieved through intricate host–pathogen interactions in immune cell aggregates called granulomas, wherein Salmonella establish favourable cellular niches to exploit while the host limits its expansion and tissue dissemination. Here, using a mouse model of persistent Salmonella infection, we identify a host-protective role for eosinophils in the control of Salmonella Typhimurium (STm) infection within the mesenteric lymph nodes, the main lymphoid tissue of STm persistence. Combining spatial transcriptomics and experimental manipulations, we found that monocytes and macrophages responding to STm infection recruited eosinophils in a C-C motif chemokine ligand 11 (CCL11)-dependent manner and enhanced their activation. The protein major basic protein, primarily expressed by eosinophils, was associated with altered macrophage polarization and bacterial control. Thus, eosinophils play a vital role in restraining Salmonella exploitation of granuloma macrophages at a key site of bacterial persistence. Eosinophils enhance granuloma-mediated control of persistent Salmonella infection in mice through CCL11-driven recruitment and MBP-dependent modulation of macrophage polarization and bacterial clearance.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 12","pages":"3176-3190"},"PeriodicalIF":19.4,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-025-02187-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145559932","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}
Pub Date : 2025-11-21DOI: 10.1038/s41564-025-02196-0
Osnat Weissberg, Dikla Aharonovich, Zhen Wu, Michael J. Follows, Daniel Sher
Phytoplankton growth and death depend on interactions with heterotrophic bacteria, yet the underlying mechanisms remain mostly unclear. Here we ask whether mathematical models explicitly representing four putative mechanisms of interaction (overflow metabolism, mixotrophy, exoenzymes and reactive oxygen species detoxification) can recapitulate diverse dynamics observed in laboratory co-cultures between the cyanobacterium Prochlorococcus and eight heterotrophic bacteria. Two distinct modes of interaction emerge from our models: (1) organic carbon and nitrogen recycling through exoenzymes or an overflow metabolism, in which the high biomass of both organisms leads to more productivity and recalcitrant organic matter, and (2) reactive oxygen species detoxification, in which a small number of ‘exploited’ heterotrophs are sufficient to support Prochlorococcus survival. Recycling is probably the main process in laboratory co-cultures. Models do not reproduce total inhibition of Prochlorococcus, suggesting that additional mechanisms such as allelopathy may be involved. The models highlight cell death and biomass recycling as unconstrained, key processes that could enhance our understanding of how interactions impact ecologically and biogeochemically important processes. Mathematical representations of overflow metabolism, mixotrophy, exoenzymes and reactive oxygen species detoxification recapitulate dynamics in co-cultures of Prochlorococcus and eight heterotrophic bacteria.
{"title":"Models and co-culture experiments assess four mechanisms of phytoplankton–bacteria interactions","authors":"Osnat Weissberg, Dikla Aharonovich, Zhen Wu, Michael J. Follows, Daniel Sher","doi":"10.1038/s41564-025-02196-0","DOIUrl":"10.1038/s41564-025-02196-0","url":null,"abstract":"Phytoplankton growth and death depend on interactions with heterotrophic bacteria, yet the underlying mechanisms remain mostly unclear. Here we ask whether mathematical models explicitly representing four putative mechanisms of interaction (overflow metabolism, mixotrophy, exoenzymes and reactive oxygen species detoxification) can recapitulate diverse dynamics observed in laboratory co-cultures between the cyanobacterium Prochlorococcus and eight heterotrophic bacteria. Two distinct modes of interaction emerge from our models: (1) organic carbon and nitrogen recycling through exoenzymes or an overflow metabolism, in which the high biomass of both organisms leads to more productivity and recalcitrant organic matter, and (2) reactive oxygen species detoxification, in which a small number of ‘exploited’ heterotrophs are sufficient to support Prochlorococcus survival. Recycling is probably the main process in laboratory co-cultures. Models do not reproduce total inhibition of Prochlorococcus, suggesting that additional mechanisms such as allelopathy may be involved. The models highlight cell death and biomass recycling as unconstrained, key processes that could enhance our understanding of how interactions impact ecologically and biogeochemically important processes. Mathematical representations of overflow metabolism, mixotrophy, exoenzymes and reactive oxygen species detoxification recapitulate dynamics in co-cultures of Prochlorococcus and eight heterotrophic bacteria.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 1","pages":"271-281"},"PeriodicalIF":19.4,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145559929","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}
Pub Date : 2025-11-18DOI: 10.1038/s41564-025-02179-1
Sean Miletic, Simoun Icho, Zhijie Li, John Tam, Elizabeth C. Rose, Cypress E. Perkins, Ali Nakhi, Xinglin Yang, Howard C. Hang, John L. Rubinstein, Peter I. Dosa, Casey M. Theriot, Roman A. Melnyk
Intestinal bile acids are a family of host and microbiota metabolites that can directly inhibit toxin B (TcdB), the primary virulence factor of Clostridioides difficile that causes infectious diarrhoea and colitis. However, the mechanism underlying the inhibition is unclear. Here we used cryogenic electron microscopy and determined the structure of TcdB bound to inhibitory bile acids cholic acid (methyl ester) and taurochenodeoxycholic acid at 2.9 Å and 3.3 Å resolution, respectively. These structures revealed that bile acids lock the C-terminal CROP domain of TcdB in a conformation that allosterically masks the two receptor-binding sites and prevents target cell recognition. Guided by the structure, we synthesized gut-restricted bile acid derivatives, designed to evade the bile acid reuptake transporters within the gut. One of the derivatives, sBA-2, was retained within the gut upon oral dosing and protected mice from toxin-induced C. difficile disease pathology. Our study uncovers the structural basis of inhibition of TcdB by bile acids and its analogues, paving the way for the development of orally deliverable therapeutics against C. difficile. A bile acid-bound structure of toxin TcdB revealed the mechanism of inhibition and guided the design of a synthetic bile acid that alleviated Clostridioides difficile infection in mice.
{"title":"Structure-guided design of a synthetic bile acid that inhibits Clostridioides difficile TcdB toxin","authors":"Sean Miletic, Simoun Icho, Zhijie Li, John Tam, Elizabeth C. Rose, Cypress E. Perkins, Ali Nakhi, Xinglin Yang, Howard C. Hang, John L. Rubinstein, Peter I. Dosa, Casey M. Theriot, Roman A. Melnyk","doi":"10.1038/s41564-025-02179-1","DOIUrl":"10.1038/s41564-025-02179-1","url":null,"abstract":"Intestinal bile acids are a family of host and microbiota metabolites that can directly inhibit toxin B (TcdB), the primary virulence factor of Clostridioides difficile that causes infectious diarrhoea and colitis. However, the mechanism underlying the inhibition is unclear. Here we used cryogenic electron microscopy and determined the structure of TcdB bound to inhibitory bile acids cholic acid (methyl ester) and taurochenodeoxycholic acid at 2.9 Å and 3.3 Å resolution, respectively. These structures revealed that bile acids lock the C-terminal CROP domain of TcdB in a conformation that allosterically masks the two receptor-binding sites and prevents target cell recognition. Guided by the structure, we synthesized gut-restricted bile acid derivatives, designed to evade the bile acid reuptake transporters within the gut. One of the derivatives, sBA-2, was retained within the gut upon oral dosing and protected mice from toxin-induced C. difficile disease pathology. Our study uncovers the structural basis of inhibition of TcdB by bile acids and its analogues, paving the way for the development of orally deliverable therapeutics against C. difficile. A bile acid-bound structure of toxin TcdB revealed the mechanism of inhibition and guided the design of a synthetic bile acid that alleviated Clostridioides difficile infection in mice.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 12","pages":"3215-3228"},"PeriodicalIF":19.4,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145536179","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}
Pub Date : 2025-11-14DOI: 10.1038/s41564-025-02185-3
Killian Scanlon, Fergus Shanahan, R. Paul Ross, Colin Hill
Bacteria have multiple mechanisms through which they sense changes in their environment and respond appropriately. In some instances, bacteria appear to retain an imprint of past events that can influence future behaviour, resembling a form of memory. This Perspective explores this concept of bacterial memory at the genetic, epigenetic, biochemical and ecological levels. We discuss how memory can prime bacteria to respond appropriately to recurring stimuli, providing fitness benefits in fluctuating environments. At the cellular level, there is evidence for memory storage mechanisms involving mutations, DNA methylation, or the inheritance of metabolites or proteins that provide a means of accessing past experiences. Complex bacterial communities can exhibit ecological memories of past environments, stored as microbiota population changes that persist or lag after acute environmental change. We review the emerging evidence supporting these concepts of microbial memory, outline some of the key molecular mechanisms, and identify research gaps and potential future applications. This Perspective discusses the concept, mechanisms and evidence for memory in bacteria at individual and community levels.
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Pub Date : 2025-11-11DOI: 10.1038/s41564-025-02204-3
Thiago Luiz Alves e Silva, Joel Vega-Rodriguez
Metarhizium fungi can be engineered to produce the volatile longifolene to attract and kill mosquitoes, offering a new approach to sustainable vector control.
绿僵菌可以产生挥发性长叶烯来吸引和杀死蚊子，为可持续的病媒控制提供了一种新的方法。
{"title":"Entomopathogenic fungi bait and kill insects with longifolene","authors":"Thiago Luiz Alves e Silva, Joel Vega-Rodriguez","doi":"10.1038/s41564-025-02204-3","DOIUrl":"10.1038/s41564-025-02204-3","url":null,"abstract":"Metarhizium fungi can be engineered to produce the volatile longifolene to attract and kill mosquitoes, offering a new approach to sustainable vector control.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 12","pages":"3043-3044"},"PeriodicalIF":19.4,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145484868","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}
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