Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging bunyavirus causing severe systemic infection with high mortality rates. Previously, SFTSV RNA was reported in the semen of infected patients, but whether SFTSV infects the male reproductive tract remains unclear. Here we demonstrate that SFTSV exhibits broad tropism for male reproductive organs in mice, resulting in low sperm count and local inflammation. SFTSV infects Leydig cells in the testis, triggering apoptosis, pyroptosis and inflammation, thereby disrupting testosterone production. Single-cell RNA sequencing identified infiltration of CCR2+ and SPP1+ macrophages expressing S100A4, a key driver of epididymal hyperinflammation and fibrosis. An S100A4 inhibitor reduced pathology and mortality in infected mice. Potential male-to-female sexual transmission risk was observed in mice. In infected patients, viral shedding in semen correlated with disease severity and spermatogenic dysfunction, with viral persistence lasting nearly 3 months after symptom onset. These findings suggest a potential risk of sexual transmission and adverse effects on male reproductive health.
{"title":"Severe fever with thrombocytopenia syndrome virus infection of the male reproductive tract induces pathology and inflammation","authors":"Yunfa Zhang, Lingyu Zhang, Huan Xu, Xiaohong Yin, Xiaojie Zheng, Ning Cui, Hongdi Lv, Xiaoai Zhang, Liqun Fang, Leike Zhang, Hongbo Chen, Wei Liu, Hao Li","doi":"10.1038/s41564-026-02298-3","DOIUrl":"https://doi.org/10.1038/s41564-026-02298-3","url":null,"abstract":"Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging bunyavirus causing severe systemic infection with high mortality rates. Previously, SFTSV RNA was reported in the semen of infected patients, but whether SFTSV infects the male reproductive tract remains unclear. Here we demonstrate that SFTSV exhibits broad tropism for male reproductive organs in mice, resulting in low sperm count and local inflammation. SFTSV infects Leydig cells in the testis, triggering apoptosis, pyroptosis and inflammation, thereby disrupting testosterone production. Single-cell RNA sequencing identified infiltration of CCR2+ and SPP1+ macrophages expressing S100A4, a key driver of epididymal hyperinflammation and fibrosis. An S100A4 inhibitor reduced pathology and mortality in infected mice. Potential male-to-female sexual transmission risk was observed in mice. In infected patients, viral shedding in semen correlated with disease severity and spermatogenic dysfunction, with viral persistence lasting nearly 3 months after symptom onset. These findings suggest a potential risk of sexual transmission and adverse effects on male reproductive health.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"17 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147506130","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 : 2026-03-25DOI: 10.1038/s41564-026-02283-w
Rebecca A. Gladstone, Maiju Pesonen, Anna K. Pöntinen, Tommi Mäklin, Neil MacAlasdair, Harry Thorpe, Yan Shao, Sudaraka Mallawaarachchi, Sergio Arredondo-Alonso, Benjamin J. Parcell, Jake David Turnbull, Gerry Tonkin-hill, Pål J. Johnsen, Ørjan Samuelsen, Nicholas R. Thomson, Trevor Lawley, Jukka Corander
Bacterial polysaccharide capsules contribute to antigenic diversity and immune evasion. Escherichia coli infections, including those caused by extraintestinal pathogenic E. coli (ExPEC), cause substantial antimicrobial resistance-associated morbidity and mortality. However, much-needed genotypic methods for E. coli capsule typing to aid epidemiological analysis and therapeutic design are lacking. Here we describe the curation of an in silico typing database for group 2 and 3 ATP-binding cassette transporter-dependent capsule (K) loci from 18,185 kps-positive E. coli genomes from all continents and its application to carriage and ExPEC disease cohorts. Capsules K1, K5 and K2 were the most common types in European BSIs, and together with K100 and K52 they were responsible for 58% of multidrug resistance, with differing associations with invasiveness. Homologous recombination, insertion sequences and plasmids were associated with capsular gene exchange. These findings improve understanding of capsule epidemiology and evolution to inform future diagnostic and therapeutic strategies to combat ExPEC infections.
{"title":"Identification of transporter-dependent capsular loci associated with the invasive potential of Escherichia coli","authors":"Rebecca A. Gladstone, Maiju Pesonen, Anna K. Pöntinen, Tommi Mäklin, Neil MacAlasdair, Harry Thorpe, Yan Shao, Sudaraka Mallawaarachchi, Sergio Arredondo-Alonso, Benjamin J. Parcell, Jake David Turnbull, Gerry Tonkin-hill, Pål J. Johnsen, Ørjan Samuelsen, Nicholas R. Thomson, Trevor Lawley, Jukka Corander","doi":"10.1038/s41564-026-02283-w","DOIUrl":"https://doi.org/10.1038/s41564-026-02283-w","url":null,"abstract":"Bacterial polysaccharide capsules contribute to antigenic diversity and immune evasion. Escherichia coli infections, including those caused by extraintestinal pathogenic E. coli (ExPEC), cause substantial antimicrobial resistance-associated morbidity and mortality. However, much-needed genotypic methods for E. coli capsule typing to aid epidemiological analysis and therapeutic design are lacking. Here we describe the curation of an in silico typing database for group 2 and 3 ATP-binding cassette transporter-dependent capsule (K) loci from 18,185 kps-positive E. coli genomes from all continents and its application to carriage and ExPEC disease cohorts. Capsules K1, K5 and K2 were the most common types in European BSIs, and together with K100 and K52 they were responsible for 58% of multidrug resistance, with differing associations with invasiveness. Homologous recombination, insertion sequences and plasmids were associated with capsular gene exchange. These findings improve understanding of capsule epidemiology and evolution to inform future diagnostic and therapeutic strategies to combat ExPEC infections.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"19 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147506129","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 : 2026-03-23DOI: 10.1038/s41564-026-02284-9
Timothy M Ghaly
{"title":"Climate change propels antibiotic resistance from soils into hospitals.","authors":"Timothy M Ghaly","doi":"10.1038/s41564-026-02284-9","DOIUrl":"https://doi.org/10.1038/s41564-026-02284-9","url":null,"abstract":"","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"112 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147502236","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 : 2026-03-23DOI: 10.1038/s41564-026-02274-x
Xiaoyu Shan, Karen Cao, Hannah Jeckel, Reinaldo E. Alcalde, Inês B. Trindade, Jarek V. Kwiecinski, Dianne K. Newman
Antibiotic resistance is a growing threat to human health and is often attributed to excessive clinical usage that selects for resistance. Although many antibiotics are derived from soil microorganisms, how environmental changes to soil ecosystems might promote resistance is poorly understood. Here we establish drought as a driving force of antibiotic resistance in the soil, with potentially far-reaching public health consequences. Across various geographic regions and soil types, we consistently observe metagenomic signatures of enrichment for antibiotic producers under drought conditions. Experimentally, we demonstrate that drought-induced lowering of water content concentrates natural antibiotics, thereby intensifying selection against sensitive strains and favouring antibiotic-resistant bacteria. Using clinical surveillance data from 116 countries, we show that the average frequency of hospital antibiotic resistance is strongly correlated with the local aridity index, even after controlling for regional income differences. Together, our findings reveal an underrecognized link between climate factors and antibiotic resistance.
{"title":"Drought drives elevated antibiotic resistance across soils","authors":"Xiaoyu Shan, Karen Cao, Hannah Jeckel, Reinaldo E. Alcalde, Inês B. Trindade, Jarek V. Kwiecinski, Dianne K. Newman","doi":"10.1038/s41564-026-02274-x","DOIUrl":"https://doi.org/10.1038/s41564-026-02274-x","url":null,"abstract":"Antibiotic resistance is a growing threat to human health and is often attributed to excessive clinical usage that selects for resistance. Although many antibiotics are derived from soil microorganisms, how environmental changes to soil ecosystems might promote resistance is poorly understood. Here we establish drought as a driving force of antibiotic resistance in the soil, with potentially far-reaching public health consequences. Across various geographic regions and soil types, we consistently observe metagenomic signatures of enrichment for antibiotic producers under drought conditions. Experimentally, we demonstrate that drought-induced lowering of water content concentrates natural antibiotics, thereby intensifying selection against sensitive strains and favouring antibiotic-resistant bacteria. Using clinical surveillance data from 116 countries, we show that the average frequency of hospital antibiotic resistance is strongly correlated with the local aridity index, even after controlling for regional income differences. Together, our findings reveal an underrecognized link between climate factors and antibiotic resistance.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"146 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147496839","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 : 2026-03-23DOI: 10.1038/s41564-026-02296-5
Delfina Fernandes Hlashwayo
{"title":"Science diplomacy, research and global health.","authors":"Delfina Fernandes Hlashwayo","doi":"10.1038/s41564-026-02296-5","DOIUrl":"https://doi.org/10.1038/s41564-026-02296-5","url":null,"abstract":"","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"35 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147502237","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}
Yellow fever virus (YFV) is an arbovirus causing substantial human morbidity and mortality. The live-attenuated 17D strain serves as vaccine and is one of the most successful vaccines so far. Receptor usage between attenuated and pathogenic YFV strains remains unclear. Here we performed a barcoded, genome-wide human open-reading frame library screen and identified LRP8 (also named APOER2) as a receptor for YFV. We show that LRP8 expression increases YFV infection (17D and two clinical strains, BJ01 and Asibi) in cell lines by promoting entry. Adeno-associated virus-mediated expression of human LRP8 in mouse liver aggravates infection and pathology of the clinical strain BJ01. LRP8 knockdown decreases YFV infection in brain cells, primary human hepatocytes and mosquitoes. LRP8 directly interacts with YFV 17D particles via the viral envelope protein. A soluble LRP8 decoy protein can block YFV 17D and BJ01 infection. Our findings provide insights for understanding YFV entry, tropism and pathogenesis.
{"title":"LRP8 is a functional receptor for yellow fever virus.","authors":"Miao Mei,Yang Yang,Zihan Zhang,Yue Yin,Jiali Tan,Chao Jiang,Yu Gao,Zhaoyang Wang,Donghong Wang,Yajing Li,Yingyi Cong,Zhiyuan Zhang,Yousong Peng,Wenjie Tan,Jiandong Li,Li Li,Hanxuan Wang,Ren Lang,Qiang He,Zihou Deng,Xiaojie Huang,Bin Luo,Chao Shan,Yonghong Zhang,Lin Mei,Gong Cheng,Xu Tan","doi":"10.1038/s41564-026-02278-7","DOIUrl":"https://doi.org/10.1038/s41564-026-02278-7","url":null,"abstract":"Yellow fever virus (YFV) is an arbovirus causing substantial human morbidity and mortality. The live-attenuated 17D strain serves as vaccine and is one of the most successful vaccines so far. Receptor usage between attenuated and pathogenic YFV strains remains unclear. Here we performed a barcoded, genome-wide human open-reading frame library screen and identified LRP8 (also named APOER2) as a receptor for YFV. We show that LRP8 expression increases YFV infection (17D and two clinical strains, BJ01 and Asibi) in cell lines by promoting entry. Adeno-associated virus-mediated expression of human LRP8 in mouse liver aggravates infection and pathology of the clinical strain BJ01. LRP8 knockdown decreases YFV infection in brain cells, primary human hepatocytes and mosquitoes. LRP8 directly interacts with YFV 17D particles via the viral envelope protein. A soluble LRP8 decoy protein can block YFV 17D and BJ01 infection. Our findings provide insights for understanding YFV entry, tropism and pathogenesis.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"11 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147483661","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 : 2026-03-19DOI: 10.1038/s41564-026-02305-7
{"title":"Metagenomic surveillance of zoonotic yellow fever and spillover dynamics at a forest-urban interface.","authors":"","doi":"10.1038/s41564-026-02305-7","DOIUrl":"https://doi.org/10.1038/s41564-026-02305-7","url":null,"abstract":"","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"58 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147483664","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 : 2026-03-19DOI: 10.1038/s41564-026-02295-6
Li Yang,Robert C Peery,Shirui Zhou,Xiaomin Chen,Leah M Farmer,Fabiola Gutierrez,Stephanie Fowler,Lanjing Zhang,Julia M Salamat,Karen Riggins,Jiejun Shi,Lanlan Shen
During weaning, the transition to solid food diversifies the gut microbiome, triggering a programmed immune response critical for long-lasting mucosal immunity. Previous work showed that the gut microbiome mediates epigenetic development in intestinal stem cells (ISCs) during suckling, but what happens during weaning is unclear. Here, genome-wide profiling revealed that weaning-driven microbiome changes shape the DNA methylome and transcriptome of murine ISCs in an IFNγ-dependent manner. Specifically, we observe demethylation of enhancer elements essential for MHC class II genes, which results in a transcriptional memory that persists through differentiation into adulthood. IFNγ blockade, or low-dose penicillin to target Gram-positive bacteria, in early life impaired microbiome-mediated epigenetic control and mucosal immunity, and exacerbated colitis. Murine organoids primed with IFNγ showed rapid, amplified transcriptional responses upon secondary stimulations. These findings reveal that early-life events alter the gut microbiome and these changes reprogramme ISC epigenetic memory to shape mucosal immunity.
{"title":"Weaning drives microbiome-mediated epigenetic regulation to shape immune memory in mice.","authors":"Li Yang,Robert C Peery,Shirui Zhou,Xiaomin Chen,Leah M Farmer,Fabiola Gutierrez,Stephanie Fowler,Lanjing Zhang,Julia M Salamat,Karen Riggins,Jiejun Shi,Lanlan Shen","doi":"10.1038/s41564-026-02295-6","DOIUrl":"https://doi.org/10.1038/s41564-026-02295-6","url":null,"abstract":"During weaning, the transition to solid food diversifies the gut microbiome, triggering a programmed immune response critical for long-lasting mucosal immunity. Previous work showed that the gut microbiome mediates epigenetic development in intestinal stem cells (ISCs) during suckling, but what happens during weaning is unclear. Here, genome-wide profiling revealed that weaning-driven microbiome changes shape the DNA methylome and transcriptome of murine ISCs in an IFNγ-dependent manner. Specifically, we observe demethylation of enhancer elements essential for MHC class II genes, which results in a transcriptional memory that persists through differentiation into adulthood. IFNγ blockade, or low-dose penicillin to target Gram-positive bacteria, in early life impaired microbiome-mediated epigenetic control and mucosal immunity, and exacerbated colitis. Murine organoids primed with IFNγ showed rapid, amplified transcriptional responses upon secondary stimulations. These findings reveal that early-life events alter the gut microbiome and these changes reprogramme ISC epigenetic memory to shape mucosal immunity.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"13 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147483662","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 : 2026-03-18DOI: 10.1038/s41564-026-02291-w
Michaela K Fiedler,Marianne S I Pandler,Ruolan Gong,Sonja Fuchs,Katharina Rox,Verena Friedrich,Dietmar Pfeiffer,Dharmesh Singh,Till Reinhardt,Cora Mibus,Matthias Huber,Corinna R Hess,Raquel Mejías-Luque,Markus Gerhard,Michael Groll,Stephan A Sieber
Metronidazole is a front-line drug for the treatment of Helicobacter pylori infections. However, its mode of action and cellular targets are poorly defined, and higher dosing and combination therapies are required to overcome resistance. Here we performed activity-based protein profiling with tailored metronidazole probes and identified chaperonin HpGroEL and thiol peroxidase HpTpx as prominent targets, the latter being essential for H. pylori survival under oxidative stress. Alkynylated ether probes exhibited enhanced antibacterial potency compared with the parent drug in vitro, including activity against resistant strains. Biological assays, chemical proteomics and co-crystallization studies confirmed target engagement, with enhanced binding of ether derivatives to HpTpx. Refined ether analogues exhibited favourable pharmacological profiles without cytotoxicity. The in vivo activity of ether analogues using an H. pylori mouse model demonstrated full bacterial eradication at low dosing of 0.3 mg kg-1 day-1. Our findings reveal that stress induction and simultaneous inhibition of the stress response represent a mechanism of this compound class.
{"title":"Metronidazole and ether derivatives target Helicobacter pylori via simultaneous stress induction and inhibition.","authors":"Michaela K Fiedler,Marianne S I Pandler,Ruolan Gong,Sonja Fuchs,Katharina Rox,Verena Friedrich,Dietmar Pfeiffer,Dharmesh Singh,Till Reinhardt,Cora Mibus,Matthias Huber,Corinna R Hess,Raquel Mejías-Luque,Markus Gerhard,Michael Groll,Stephan A Sieber","doi":"10.1038/s41564-026-02291-w","DOIUrl":"https://doi.org/10.1038/s41564-026-02291-w","url":null,"abstract":"Metronidazole is a front-line drug for the treatment of Helicobacter pylori infections. However, its mode of action and cellular targets are poorly defined, and higher dosing and combination therapies are required to overcome resistance. Here we performed activity-based protein profiling with tailored metronidazole probes and identified chaperonin HpGroEL and thiol peroxidase HpTpx as prominent targets, the latter being essential for H. pylori survival under oxidative stress. Alkynylated ether probes exhibited enhanced antibacterial potency compared with the parent drug in vitro, including activity against resistant strains. Biological assays, chemical proteomics and co-crystallization studies confirmed target engagement, with enhanced binding of ether derivatives to HpTpx. Refined ether analogues exhibited favourable pharmacological profiles without cytotoxicity. The in vivo activity of ether analogues using an H. pylori mouse model demonstrated full bacterial eradication at low dosing of 0.3 mg kg-1 day-1. Our findings reveal that stress induction and simultaneous inhibition of the stress response represent a mechanism of this compound class.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"12 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147478544","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 : 2026-03-16DOI: 10.1038/s41564-026-02285-8
Abigail Glascock, Cole Maguire, Hoang Van Phan, Emily C. Lydon, Joanna Schaenman, Carolyn S. Calfee, Esther Melamed, John Greenland, David B. Corry, Farrah Kheradmand, Lindsey R. Baden, Rafick Sekaly, Grace A. McComsey, Elias K. Haddad, Charles B. Cairns, Linda N. Geng, Bali Pulendran, Ana Fernandez-Sesma, Viviana Simon, Jordan P. Metcalf, Nelson I. Agudelo Higuita, William B. Messer, Mark M. Davis, Kari C. Nadeau, Monica Kraft, Christian Bime, David J. Erle, Mark A. Atkinson, Scott C. Brakenridge, Lauren I. R. Ehrlich, Ruth R. Montgomery, Albert C. Shaw, Catherine L. Hough, David A. Hafler, Alison D. Augustine, Patrice M. Becker, Bjoern Peters, Al Ozonoff, Annmarie Hoch, Seunghee Kim-Schulze, Florian Krammer, Steven Bosinger, Walter Eckalbar, Matthew C. Altman, Michael Wilson, Leying Guan, Holden Maecker, Hanno Steen, IMPACC Network, Joann Diray-Arce
Azithromycin is a widely used antibiotic and was frequently used to treat hospitalized patients during the COVID-19 pandemic. The impact of empiric azithromycin use on the respiratory microbiome in patients with viral respiratory infections is unclear. Here we used longitudinal metatranscriptomics on nasal swabs from a prospective multicentre cohort of 1,164 patients hospitalized for COVID-19. We compared the upper respiratory microbiome, resistome and systemic immune response in patients treated with azithromycin (n = 366) with those who received no antibiotics (n = 474) or other antibiotics (n = 324). We found that azithromycin altered microbiome composition and increased the expression and relative proportion of macrolide/lincosamide/streptogramin (MLS) resistance genes. These changes occurred after 1 day of exposure and persisted for over a week. MLS resistance gene expression was associated with commensals and potential pathogens, while there were no differences in host inflammatory gene expression in blood and airways. This demonstrates that empiric azithromycin treatment impacts the upper respiratory microbiome and resistome without apparent anti-inflammatory benefit.
{"title":"Empiric azithromycin alters the upper respiratory microbiome and resistome without anti-inflammatory benefit in COVID-19","authors":"Abigail Glascock, Cole Maguire, Hoang Van Phan, Emily C. Lydon, Joanna Schaenman, Carolyn S. Calfee, Esther Melamed, John Greenland, David B. Corry, Farrah Kheradmand, Lindsey R. Baden, Rafick Sekaly, Grace A. McComsey, Elias K. Haddad, Charles B. Cairns, Linda N. Geng, Bali Pulendran, Ana Fernandez-Sesma, Viviana Simon, Jordan P. Metcalf, Nelson I. Agudelo Higuita, William B. Messer, Mark M. Davis, Kari C. Nadeau, Monica Kraft, Christian Bime, David J. Erle, Mark A. Atkinson, Scott C. Brakenridge, Lauren I. R. Ehrlich, Ruth R. Montgomery, Albert C. Shaw, Catherine L. Hough, David A. Hafler, Alison D. Augustine, Patrice M. Becker, Bjoern Peters, Al Ozonoff, Annmarie Hoch, Seunghee Kim-Schulze, Florian Krammer, Steven Bosinger, Walter Eckalbar, Matthew C. Altman, Michael Wilson, Leying Guan, Holden Maecker, Hanno Steen, IMPACC Network, Joann Diray-Arce","doi":"10.1038/s41564-026-02285-8","DOIUrl":"https://doi.org/10.1038/s41564-026-02285-8","url":null,"abstract":"Azithromycin is a widely used antibiotic and was frequently used to treat hospitalized patients during the COVID-19 pandemic. The impact of empiric azithromycin use on the respiratory microbiome in patients with viral respiratory infections is unclear. Here we used longitudinal metatranscriptomics on nasal swabs from a prospective multicentre cohort of 1,164 patients hospitalized for COVID-19. We compared the upper respiratory microbiome, resistome and systemic immune response in patients treated with azithromycin (n = 366) with those who received no antibiotics (n = 474) or other antibiotics (n = 324). We found that azithromycin altered microbiome composition and increased the expression and relative proportion of macrolide/lincosamide/streptogramin (MLS) resistance genes. These changes occurred after 1 day of exposure and persisted for over a week. MLS resistance gene expression was associated with commensals and potential pathogens, while there were no differences in host inflammatory gene expression in blood and airways. This demonstrates that empiric azithromycin treatment impacts the upper respiratory microbiome and resistome without apparent anti-inflammatory benefit.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"95 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147465328","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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