Pub Date : 2026-02-19DOI: 10.1038/s41564-026-02265-y
Jessica Braverman, Ian R. Monk, Adrianna M. Turner, Asolina Braun, Heran Zhang, Shanzou Chung, Claerwen M. Jones, Pirooz Zareie, Nicole L. La Gruta, Joanne Rimmer, Glen P. Carter, Benjamin P. Howden, Nancy Wang, Anthony W. Purcell, Timothy P. Stinear, Linda M. Wakim
Vaccines are effective and much-needed tools against bacterial infection, which mitigate multidrug resistance; however, selection of bacterial antigens that elicit protection and contribute to effective vaccines remains challenging. Here we use immunopeptidomics to identify CD4+ T cell vaccine targets in methicillin-resistant Staphylococcus aureus, a clinically significant, antibiotic-resistant bacterium that is susceptible to T cell-mediated control. We identified a highly conserved, immunodominant CD4+ T cell epitope in S. aureus that is derived from the core DNA-binding protein Hu (Hup). This epitope was shared across a range of clinically relevant streptococcal and staphylococcal species, and cross-species-reactive Hup-specific CD4+ T cells were found in both mice and humans. Immunization of mice with the Hup epitope resulted in the development of broadly protective CD4+ T cell immunity capable of limiting disease severity following infection with S. aureus and Streptococcus pneumoniae. These findings suggest that vaccines incorporating antigens derived from core genes conserved across species might confer broad-spectrum protection against multiple clinically relevant, antibiotic-resistant streptococcal and staphylococcal strains. Immunopeptidomics identify CD4⁺ T cell epitopes from the conserved bacterial Hup protein that confer protection against multiple bacterial infections in mice suggesting potential for development of broader-spectrum vaccines against staphylococci and streptococci.
{"title":"Conserved CD4+ T cell staphylococcal and streptococcal epitopes enable broad-acting vaccines in mice","authors":"Jessica Braverman, Ian R. Monk, Adrianna M. Turner, Asolina Braun, Heran Zhang, Shanzou Chung, Claerwen M. Jones, Pirooz Zareie, Nicole L. La Gruta, Joanne Rimmer, Glen P. Carter, Benjamin P. Howden, Nancy Wang, Anthony W. Purcell, Timothy P. Stinear, Linda M. Wakim","doi":"10.1038/s41564-026-02265-y","DOIUrl":"10.1038/s41564-026-02265-y","url":null,"abstract":"Vaccines are effective and much-needed tools against bacterial infection, which mitigate multidrug resistance; however, selection of bacterial antigens that elicit protection and contribute to effective vaccines remains challenging. Here we use immunopeptidomics to identify CD4+ T cell vaccine targets in methicillin-resistant Staphylococcus aureus, a clinically significant, antibiotic-resistant bacterium that is susceptible to T cell-mediated control. We identified a highly conserved, immunodominant CD4+ T cell epitope in S. aureus that is derived from the core DNA-binding protein Hu (Hup). This epitope was shared across a range of clinically relevant streptococcal and staphylococcal species, and cross-species-reactive Hup-specific CD4+ T cells were found in both mice and humans. Immunization of mice with the Hup epitope resulted in the development of broadly protective CD4+ T cell immunity capable of limiting disease severity following infection with S. aureus and Streptococcus pneumoniae. These findings suggest that vaccines incorporating antigens derived from core genes conserved across species might confer broad-spectrum protection against multiple clinically relevant, antibiotic-resistant streptococcal and staphylococcal strains. Immunopeptidomics identify CD4⁺ T cell epitopes from the conserved bacterial Hup protein that confer protection against multiple bacterial infections in mice suggesting potential for development of broader-spectrum vaccines against staphylococci and streptococci.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 3","pages":"731-746"},"PeriodicalIF":19.4,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146223319","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 : 2026-02-18DOI: 10.1038/s41564-026-02268-9
Gretchen Diffendall, Perine Millot, Patty Chen, Balotin Fogang, Dominique Dorin-Semblat, Fanny Aprahamian, Sylvère Durand, Benoît Gamain, Antoine Claessens, Artur Scherf
In malaria-endemic regions, asymptomatic Plasmodium falciparum infections during periods of low transmission alternate with symptomatic infections during periods of high transmission. The mechanisms underlying P. falciparum persistence without causing symptoms during low-transmission periods remain unclear. Here we analysed the plasma metabolome (n = 199) of individuals in the Gambia, West Africa, during the high and low malaria transmission periods. We observed significant metabolome changes associated with seasonality and to a lesser extent with malaria pathogenicity. We show that plasma levels of taurine, an amino sulfonic acid, increase longitudinally during periods of low transmission. Although taurine showed no effect on the development of cultured parasites in vitro, it strongly inhibited and prevented malaria-infected red blood cell (iRBC) adhesion via PfEMP1 to the common adhesion receptor CD36 and the endothelial protein C receptor, which is linked to cerebral malaria. We reveal a role for taurine in reducing cytoadhesion, which could inform strategies to reduce symptomatic malaria in sub-Saharan Africa. Seasonal metabolomics revealed that taurine increases during low malaria transmission and is linked to asymptomatic Plasmodium falciparum infection.
{"title":"Longitudinal plasma metabolomics reveals a role for taurine in asymptomatic malaria and seasonal persistence","authors":"Gretchen Diffendall, Perine Millot, Patty Chen, Balotin Fogang, Dominique Dorin-Semblat, Fanny Aprahamian, Sylvère Durand, Benoît Gamain, Antoine Claessens, Artur Scherf","doi":"10.1038/s41564-026-02268-9","DOIUrl":"10.1038/s41564-026-02268-9","url":null,"abstract":"In malaria-endemic regions, asymptomatic Plasmodium falciparum infections during periods of low transmission alternate with symptomatic infections during periods of high transmission. The mechanisms underlying P. falciparum persistence without causing symptoms during low-transmission periods remain unclear. Here we analysed the plasma metabolome (n = 199) of individuals in the Gambia, West Africa, during the high and low malaria transmission periods. We observed significant metabolome changes associated with seasonality and to a lesser extent with malaria pathogenicity. We show that plasma levels of taurine, an amino sulfonic acid, increase longitudinally during periods of low transmission. Although taurine showed no effect on the development of cultured parasites in vitro, it strongly inhibited and prevented malaria-infected red blood cell (iRBC) adhesion via PfEMP1 to the common adhesion receptor CD36 and the endothelial protein C receptor, which is linked to cerebral malaria. We reveal a role for taurine in reducing cytoadhesion, which could inform strategies to reduce symptomatic malaria in sub-Saharan Africa. Seasonal metabolomics revealed that taurine increases during low malaria transmission and is linked to asymptomatic Plasmodium falciparum infection.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 3","pages":"678-689"},"PeriodicalIF":19.4,"publicationDate":"2026-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146210123","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 : 2026-02-17DOI: 10.1038/s41564-026-02270-1
Yabing Song, Jinxin Chen, Junhua Wan, Jiamo Zhang, Qizheng Liu, Fei Sun, Hanlin Zhang, Yuru Guo, Eve W. L. Chow, Yali Chen, Ziyu Yan, Jianbin Wang, Kun Chen, Yue Wang, Jiaxin Gao
Candida auris is an emerging fungal pathogen notable for its intrinsically high resistance to fluconazole, the most prescribed antifungal drug. However, the genetic regulators underlying fluconazole susceptibility in C. auris remain unclear. Here we performed a pooled screen of piggyBac (PB) transposition mutants and identified significant enrichment of mitochondrial genes whose inactivation reduces fluconazole susceptibility. A genome-wide genetic interaction analysis of a mitochondrial gene deletion mutant, pet309Δ, suggests that the vacuolar calcium pump homologue CDT1 (Calcium and Drug Transporter 1) is responsible for its reduced fluconazole susceptibility. Fluconazole induces significant upregulation of CDT1 through the calcineurin signalling pathway. Cdt1, beyond its canonical calcium-pumping function, has evolved another function in mediating fluconazole efflux through its fluconazole-induced, calcineurin- and ATP hydrolysis-dependent plasma membrane localization. In addition, Cdt1 accelerates the evolution of fluconazole resistance or tolerance, and its transcript levels are substantially elevated across resistant clinical isolates. Our findings reveal a neofunctionalized role for Cdt1 in mediating fluconazole efflux in C. auris. The relocalization of the vacuolar calcium pump Cdt1 to the plasma membrane contributes to fluconazole adaptation in Candida auris.
{"title":"Candida auris vacuolar calcium pump mediates fluconazole efflux and resistance evolution","authors":"Yabing Song, Jinxin Chen, Junhua Wan, Jiamo Zhang, Qizheng Liu, Fei Sun, Hanlin Zhang, Yuru Guo, Eve W. L. Chow, Yali Chen, Ziyu Yan, Jianbin Wang, Kun Chen, Yue Wang, Jiaxin Gao","doi":"10.1038/s41564-026-02270-1","DOIUrl":"10.1038/s41564-026-02270-1","url":null,"abstract":"Candida auris is an emerging fungal pathogen notable for its intrinsically high resistance to fluconazole, the most prescribed antifungal drug. However, the genetic regulators underlying fluconazole susceptibility in C. auris remain unclear. Here we performed a pooled screen of piggyBac (PB) transposition mutants and identified significant enrichment of mitochondrial genes whose inactivation reduces fluconazole susceptibility. A genome-wide genetic interaction analysis of a mitochondrial gene deletion mutant, pet309Δ, suggests that the vacuolar calcium pump homologue CDT1 (Calcium and Drug Transporter 1) is responsible for its reduced fluconazole susceptibility. Fluconazole induces significant upregulation of CDT1 through the calcineurin signalling pathway. Cdt1, beyond its canonical calcium-pumping function, has evolved another function in mediating fluconazole efflux through its fluconazole-induced, calcineurin- and ATP hydrolysis-dependent plasma membrane localization. In addition, Cdt1 accelerates the evolution of fluconazole resistance or tolerance, and its transcript levels are substantially elevated across resistant clinical isolates. Our findings reveal a neofunctionalized role for Cdt1 in mediating fluconazole efflux in C. auris. The relocalization of the vacuolar calcium pump Cdt1 to the plasma membrane contributes to fluconazole adaptation in Candida auris.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 3","pages":"786-801"},"PeriodicalIF":19.4,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146204971","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 : 2026-02-16DOI: 10.1038/s41564-025-02253-8
Stavros Bashiardes, Melina Heinemann, Lorenz Adlung, Rafael Valdés-Mas, Jemal Ali Mahdi, Samuel P. Nobs, Timur Tuganbaev, Takahiro Yamada, Max Horn, Uria Mor, Yotam Cohen, Sarah Israel, Maya Korem, Yonatan Oster, Karen Olshtain-Pops, Efrat Orenbuch-Harroch, Muhammed Dervis Arslan, Shahar Molina, Maya Zur, Shimrit Eliyahu-Miller, Aurélie Bukimer, Sara Federici, Mally Dori-Bachash, Nira Amar, Daniel Elbirt, Ronit Cohen-Poradosu, Dan Turner, Tiberiu Hershcovici, Elez Vainer, Noa Stettner, Alon Harmelin, Hailay Gebremeskel, Yazezew Kebede, Sabine Schmidt, Niv Zmora, Arunraj Dhamodaran, Jens Puschhof, Zvi Bentwich, Hagit Shapiro, Ido Amit, Hila Elinav, Eran Elinav
The gut microbiome of people living with human immunodeficiency virus (PLWH) has been characterized, but its role in influencing host immunity and associated clinical features are unclear. Here we used shotgun metagenomics to characterize the faecal microbiome of two geographically distinct cohorts of PLWH and healthy controls in Israel and Ethiopia. We uncovered disease-specific, geographically divergent microbial patterns including a shift from Bacteroides to Prevotella species in an Israeli cohort and multiple Enterobacteriaceae species including Escherichia coli and Klebsiella quasivariicola in an Ethiopian cohort. We identified correlations between human immunodeficiency virus-related dysbiosis and the extent of systemic immunodeficiency, as proxied by peripheral CD4+ T cell counts. Faecal microbiome transplantation from PLWH with high peripheral CD4+ T cell counts induced colonic epithelium-associated CD4+ T cells in germ-free or antibiotic-treated recipient mice. Impaired epithelium-associated lymphocyte induction in recipients of faecal microbiome transplantation from severely immunodeficient PLWH donors was associated with altered protection from Cryptosporidium parvum infection. Collectively, our results suggest a link between systemic immunodeficiency and associated intestinal dysbiosis in PLWH, resulting in impaired gut mucosal immunity. Human immunodeficiency virus (HIV)-associated gut microbiome dysbiosis correlates with systemic immunodeficiency and opportunistic gut infections. Faecal microbiome transplantation from people living with HIV with high peripheral CD4+ T cell counts improved intestinal immunity and protection against Cryptosporidium parvum in mice.
{"title":"Human immunodeficiency virus-associated gut microbiome impacts systemic immunodeficiency and susceptibility to opportunistic gut infection","authors":"Stavros Bashiardes, Melina Heinemann, Lorenz Adlung, Rafael Valdés-Mas, Jemal Ali Mahdi, Samuel P. Nobs, Timur Tuganbaev, Takahiro Yamada, Max Horn, Uria Mor, Yotam Cohen, Sarah Israel, Maya Korem, Yonatan Oster, Karen Olshtain-Pops, Efrat Orenbuch-Harroch, Muhammed Dervis Arslan, Shahar Molina, Maya Zur, Shimrit Eliyahu-Miller, Aurélie Bukimer, Sara Federici, Mally Dori-Bachash, Nira Amar, Daniel Elbirt, Ronit Cohen-Poradosu, Dan Turner, Tiberiu Hershcovici, Elez Vainer, Noa Stettner, Alon Harmelin, Hailay Gebremeskel, Yazezew Kebede, Sabine Schmidt, Niv Zmora, Arunraj Dhamodaran, Jens Puschhof, Zvi Bentwich, Hagit Shapiro, Ido Amit, Hila Elinav, Eran Elinav","doi":"10.1038/s41564-025-02253-8","DOIUrl":"10.1038/s41564-025-02253-8","url":null,"abstract":"The gut microbiome of people living with human immunodeficiency virus (PLWH) has been characterized, but its role in influencing host immunity and associated clinical features are unclear. Here we used shotgun metagenomics to characterize the faecal microbiome of two geographically distinct cohorts of PLWH and healthy controls in Israel and Ethiopia. We uncovered disease-specific, geographically divergent microbial patterns including a shift from Bacteroides to Prevotella species in an Israeli cohort and multiple Enterobacteriaceae species including Escherichia coli and Klebsiella quasivariicola in an Ethiopian cohort. We identified correlations between human immunodeficiency virus-related dysbiosis and the extent of systemic immunodeficiency, as proxied by peripheral CD4+ T cell counts. Faecal microbiome transplantation from PLWH with high peripheral CD4+ T cell counts induced colonic epithelium-associated CD4+ T cells in germ-free or antibiotic-treated recipient mice. Impaired epithelium-associated lymphocyte induction in recipients of faecal microbiome transplantation from severely immunodeficient PLWH donors was associated with altered protection from Cryptosporidium parvum infection. Collectively, our results suggest a link between systemic immunodeficiency and associated intestinal dysbiosis in PLWH, resulting in impaired gut mucosal immunity. Human immunodeficiency virus (HIV)-associated gut microbiome dysbiosis correlates with systemic immunodeficiency and opportunistic gut infections. Faecal microbiome transplantation from people living with HIV with high peripheral CD4+ T cell counts improved intestinal immunity and protection against Cryptosporidium parvum in mice.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 3","pages":"690-703"},"PeriodicalIF":19.4,"publicationDate":"2026-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146204973","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 : 2026-02-13DOI: 10.1038/s41564-026-02280-z
Michael A. Brockhurst, Joanne L. Fothergill, Stineke van Houte, Edze R. Westra
On 25 November 2025, the international phage therapy research and biotechnology communities gathered in Liverpool, UK, to discuss progress in implementing clinical phage therapies and the latest technological breakthroughs in phage biology and engineering, while UK regulators and health agencies provided the latest guidance.
{"title":"Realizing phage therapy in the UK","authors":"Michael A. Brockhurst, Joanne L. Fothergill, Stineke van Houte, Edze R. Westra","doi":"10.1038/s41564-026-02280-z","DOIUrl":"10.1038/s41564-026-02280-z","url":null,"abstract":"On 25 November 2025, the international phage therapy research and biotechnology communities gathered in Liverpool, UK, to discuss progress in implementing clinical phage therapies and the latest technological breakthroughs in phage biology and engineering, while UK regulators and health agencies provided the latest guidance.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 3","pages":"619-621"},"PeriodicalIF":19.4,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146195068","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 : 2026-02-12DOI: 10.1038/s41564-026-02262-1
Ines Ambite, Adrian Pilatz, Mareike Buch-Heberling, Shahram Ahmadi, Gabriela Godaly, Florian Wagenlehner, Catharina Svanborg
Cystitis is a bacterial infection of the bladder that occurs in about half of women at least once in their lifetime. Antibiotics such as nitrofurantoin are used to treat cystitis, but antibiotic resistance is a concern, especially for recurrent infections. Here we report an open-label, randomized, single-centre, phase 2 study to analyse the acute and long-term safety and efficacy of the IL-1 receptor antagonist anakinra, compared with nitrofurantoin, in recurrent cystitis. A total of 30 adult female patients with a documented history of recurrent cystitis and a current acute cystitis episode were randomized in a 2:1 ratio to treatment with anakinra (n = 20) or nitrofurantoin (n = 10) for 5 days. Primary and secondary efficacy end-points were reached, defined as the reduction in typical symptoms, measured by the acute cystitis symptom score (day 5), longitudinal symptom scores, recurrence rates, quality of life, gene expression analysis and microbiology at follow-up on days 15 and 30 and at 6 months. Symptom scores were decreased in the anakinra (P < 0.001) and nitrofurantoin (P < 0.001) arms after 5 days and remained low after 15 days, 30 days and 6 months. Recurrences were less frequent after 6 months in both treatment groups compared with the 6-month pre-enrolment history (P < 0.001 for anakinra and P = 0.004 for nitrofurantoin), and the quality of life was increased, without adverse effects. Immune gene expression was rapidly inhibited in the anakinra-treated patients but not in the nitrofurantoin group. Targeted innate immune inhibition therapy shows non-inferiority to nitrofurantoin in patients with recurrent acute cystitis. German Clinical Trials Register ID: DRKS00025964 . An open-label, randomized, single-centre, phase 2 study shows that the IL-1 receptor antagonist anakinra shows non-inferiority to the antibiotic nitrofurantoin in patients with recurrent acute cystitis.
{"title":"Targeted innate immune inhibition therapy compared with antibiotics for recurrent acute cystitis: a randomized, open-label phase 2 trial","authors":"Ines Ambite, Adrian Pilatz, Mareike Buch-Heberling, Shahram Ahmadi, Gabriela Godaly, Florian Wagenlehner, Catharina Svanborg","doi":"10.1038/s41564-026-02262-1","DOIUrl":"10.1038/s41564-026-02262-1","url":null,"abstract":"Cystitis is a bacterial infection of the bladder that occurs in about half of women at least once in their lifetime. Antibiotics such as nitrofurantoin are used to treat cystitis, but antibiotic resistance is a concern, especially for recurrent infections. Here we report an open-label, randomized, single-centre, phase 2 study to analyse the acute and long-term safety and efficacy of the IL-1 receptor antagonist anakinra, compared with nitrofurantoin, in recurrent cystitis. A total of 30 adult female patients with a documented history of recurrent cystitis and a current acute cystitis episode were randomized in a 2:1 ratio to treatment with anakinra (n = 20) or nitrofurantoin (n = 10) for 5 days. Primary and secondary efficacy end-points were reached, defined as the reduction in typical symptoms, measured by the acute cystitis symptom score (day 5), longitudinal symptom scores, recurrence rates, quality of life, gene expression analysis and microbiology at follow-up on days 15 and 30 and at 6 months. Symptom scores were decreased in the anakinra (P < 0.001) and nitrofurantoin (P < 0.001) arms after 5 days and remained low after 15 days, 30 days and 6 months. Recurrences were less frequent after 6 months in both treatment groups compared with the 6-month pre-enrolment history (P < 0.001 for anakinra and P = 0.004 for nitrofurantoin), and the quality of life was increased, without adverse effects. Immune gene expression was rapidly inhibited in the anakinra-treated patients but not in the nitrofurantoin group. Targeted innate immune inhibition therapy shows non-inferiority to nitrofurantoin in patients with recurrent acute cystitis. German Clinical Trials Register ID: DRKS00025964 . An open-label, randomized, single-centre, phase 2 study shows that the IL-1 receptor antagonist anakinra shows non-inferiority to the antibiotic nitrofurantoin in patients with recurrent acute cystitis.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 3","pages":"638-647"},"PeriodicalIF":19.4,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-026-02262-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146181203","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 : 2026-02-06DOI: 10.1038/s41564-026-02267-w
Lejla Daruka, Petra Szili, Márton Simon Czikkely, Zoltán Farkas, Csaba Pál
{"title":"Addendum: ESKAPE pathogens rapidly develop resistance against antibiotics in development in vitro","authors":"Lejla Daruka, Petra Szili, Márton Simon Czikkely, Zoltán Farkas, Csaba Pál","doi":"10.1038/s41564-026-02267-w","DOIUrl":"10.1038/s41564-026-02267-w","url":null,"abstract":"","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 3","pages":"833-835"},"PeriodicalIF":19.4,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-026-02267-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132301","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 : 2026-02-05DOI: 10.1038/s41564-026-02259-w
H. Krukowski, S. Valkenburg, A. Vich Vila, L. F. Maciel, J. F. Vázquez-Castellanos, T. Gryp, M. Joossens, W. Van Biesen, F. Verbeke, M. Derrien, G. R. B. Huys, G. Glorieux, J. Raes
Despite recent progress, microbial associations reported in chronic kidney disease (CKD) remain inconsistent. Here we combined quantitative faecal metagenomics (n = 130) and cross-study biomarker comparisons (ntotal = 4,420) to study microbiome associations with estimated glomerular filtration rate (eGFR; kidney function) and 4-year CKD progression. Intestinal transit time (ITT) and medications significantly explained microbiome variation, surpassing eGFR-related effects. Lower eGFR was associated with increased p-cresol and indole biosynthetic potential and reduced plant-to-animal CAZyme ratios. This was consistent with community-wide saccharolytic-to-proteolytic microbiome transitions linked to dietary guidelines and slowed-down ITT. Peritoneal dialysis patients showed distinct microbiome dysbiosis accompanied by increased intestinal inflammation. Only Escherichia coli, an unnamed Alistipes species and Bifidobacterium adolescentis were covariate-independent markers for eGFR, but neither these nor previous microbial markers convincingly replicated across 11 studies. No predictors for CKD progression were found. Nevertheless, our study adds insight into plausible ITT and nutrition-related effects, highlighting their potential in CKD interventions. A covariate-aware analysis reveals that microbiome changes in the gut of patients with chronic kidney disease are better explained by intestinal transit time than by kidney function.
{"title":"Host factors dictate gut microbiome alterations in chronic kidney disease more strongly than kidney function","authors":"H. Krukowski, S. Valkenburg, A. Vich Vila, L. F. Maciel, J. F. Vázquez-Castellanos, T. Gryp, M. Joossens, W. Van Biesen, F. Verbeke, M. Derrien, G. R. B. Huys, G. Glorieux, J. Raes","doi":"10.1038/s41564-026-02259-w","DOIUrl":"10.1038/s41564-026-02259-w","url":null,"abstract":"Despite recent progress, microbial associations reported in chronic kidney disease (CKD) remain inconsistent. Here we combined quantitative faecal metagenomics (n = 130) and cross-study biomarker comparisons (ntotal = 4,420) to study microbiome associations with estimated glomerular filtration rate (eGFR; kidney function) and 4-year CKD progression. Intestinal transit time (ITT) and medications significantly explained microbiome variation, surpassing eGFR-related effects. Lower eGFR was associated with increased p-cresol and indole biosynthetic potential and reduced plant-to-animal CAZyme ratios. This was consistent with community-wide saccharolytic-to-proteolytic microbiome transitions linked to dietary guidelines and slowed-down ITT. Peritoneal dialysis patients showed distinct microbiome dysbiosis accompanied by increased intestinal inflammation. Only Escherichia coli, an unnamed Alistipes species and Bifidobacterium adolescentis were covariate-independent markers for eGFR, but neither these nor previous microbial markers convincingly replicated across 11 studies. No predictors for CKD progression were found. Nevertheless, our study adds insight into plausible ITT and nutrition-related effects, highlighting their potential in CKD interventions. A covariate-aware analysis reveals that microbiome changes in the gut of patients with chronic kidney disease are better explained by intestinal transit time than by kidney function.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 3","pages":"664-677"},"PeriodicalIF":19.4,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-026-02259-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146125692","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 : 2026-02-03DOI: 10.1038/s41564-026-02275-w
A near-complete model for the complex structure of the Campylobacter jejuni flagellar motor revealed different mechanisms of assembly, activation and stability from the simple ‘classical’ flagellar model. Some of the additional motor structures in C. jejuni are conserved and only found in species of Campylobacterota, whose ancestor likely co-opted type IV pilus components from bacteria in the deep ocean.
{"title":"The building blocks of one of the most complex flagellar nanomachines","authors":"","doi":"10.1038/s41564-026-02275-w","DOIUrl":"10.1038/s41564-026-02275-w","url":null,"abstract":"A near-complete model for the complex structure of the Campylobacter jejuni flagellar motor revealed different mechanisms of assembly, activation and stability from the simple ‘classical’ flagellar model. Some of the additional motor structures in C. jejuni are conserved and only found in species of Campylobacterota, whose ancestor likely co-opted type IV pilus components from bacteria in the deep ocean.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 3","pages":"622-623"},"PeriodicalIF":19.4,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146113781","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 : 2026-02-02DOI: 10.1038/s41564-026-02263-0
Mariah Hassert, Lisa L. Drewry, Lecia L. Pewe, Lisa S. Hancox, Rui He, Sahaana Arumugam, Madison R. Mix, Aliasger K. Salem, John T. Harty
Immunization with radiation-attenuated sporozoites (RAS) drives effective sterilizing immunity against liver-stage Plasmodium infection. However, protection is compromised in individuals living in malaria endemic regions and the mechanisms of vaccine failure are unclear. Here we show that previous blood-stage exposure in a mouse model of Plasmodium yoelii infection compromises Plasmodium berghei RAS-induced essential CD8+ T cell responses and subsequent protection. The persisting malarial pigment haemozoin mediates impaired CD8+ T cell responses owing to impaired antigen uptake by dendritic cells, leading to reduced T cell activation. We designed a lipid nanoparticle-encapsulated mRNA vaccine that encodes a string of Plasmodium CD8+ T cell epitopes, which overcomes the defective T cell response and restores protection in Plasmodium-exposed mice. A combined RAS-plus-mRNA vaccine regimen enhances liver-resident memory T cells and protection in murine malaria-experienced hosts. The identification of haemozoin as a potential obstacle to vaccine efficacy in malaria endemic areas can inform the design of more effective malaria vaccines. Previous malaria exposure weakens whole-parasite malaria vaccines by leaving haemozoin, which impairs T cell activation. An mRNA vaccine bypasses this block, restores protective T cells and improves protection when combined with whole-sporozoite vaccination.
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