Pub Date : 2024-10-23DOI: 10.1038/s41564-024-01840-5
Tridib Mahata, Katarzyna Kanarek, Moran G. Goren, Rameshkumar Marimuthu Ragavan, Eran Bosis, Udi Qimron, Dor Salomon
The evolutionary arms race between bacteria and phages led to the emergence of bacterial immune systems whose diversity and dynamics remain poorly understood. Here we use comparative genomics to describe a widespread genetic element, defined by the presence of the Gamma-Mobile-Trio (GMT) proteins, that serves as a reservoir of offensive and defensive tools. We demonstrate, using Vibrio parahaemolyticus as a model, that GMT-containing genomic islands are active mobile elements. Furthermore, we show that GMT islands’ cargoes contain various anti-phage defence systems, antibacterial type VI secretion system (T6SS) effectors and antibiotic-resistance genes. We reveal four anti-phage defence systems encoded within GMT islands and further characterize one system, GAPS1, showing it is triggered by a phage capsid protein to induce cell dormancy. Our findings underscore the need to broaden the concept of ‘defence islands’ to include defensive and offensive tools, as both share the same mobile elements for dissemination.
{"title":"Gamma-Mobile-Trio systems are mobile elements rich in bacterial defensive and offensive tools","authors":"Tridib Mahata, Katarzyna Kanarek, Moran G. Goren, Rameshkumar Marimuthu Ragavan, Eran Bosis, Udi Qimron, Dor Salomon","doi":"10.1038/s41564-024-01840-5","DOIUrl":"https://doi.org/10.1038/s41564-024-01840-5","url":null,"abstract":"<p>The evolutionary arms race between bacteria and phages led to the emergence of bacterial immune systems whose diversity and dynamics remain poorly understood. Here we use comparative genomics to describe a widespread genetic element, defined by the presence of the Gamma-Mobile-Trio (GMT) proteins, that serves as a reservoir of offensive and defensive tools. We demonstrate, using <i>Vibrio parahaemolyticus</i> as a model, that GMT-containing genomic islands are active mobile elements. Furthermore, we show that GMT islands’ cargoes contain various anti-phage defence systems, antibacterial type VI secretion system (T6SS) effectors and antibiotic-resistance genes. We reveal four anti-phage defence systems encoded within GMT islands and further characterize one system, GAPS1, showing it is triggered by a phage capsid protein to induce cell dormancy. Our findings underscore the need to broaden the concept of ‘defence islands’ to include defensive and offensive tools, as both share the same mobile elements for dissemination.</p>","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"225 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142487416","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}
Microorganisms use toxins to kill competing microorganisms or eukaryotic cells. Polymorphic toxins are proteins that encode carboxy-terminal toxin domains. Here we developed a computational approach to identify previously undiscovered, conserved toxin domains of polymorphic toxins within 105,438 microbial genomes. We validated nine short toxins, showing that they cause cell death upon heterologous expression in either Escherichia coli or Saccharomyces cerevisiae. Five cognate immunity genes that neutralize the toxins were also discovered. The toxins are encoded by 2.2% of sequenced bacteria. A subset of the toxins exhibited potent antifungal activity against various pathogenic fungi but not against two invertebrate model organisms or macrophages. Experimental validation suggested that these toxins probably target the cell membrane or DNA or inhibit cell division. Further characterization and structural analysis of two toxin–immunity protein complexes confirmed DNase activity. These findings expand our knowledge of microbial toxins involved in inter-microbial competition that may have the potential for clinical and biotechnological applications. Genome sequence mining and computational analyses lead to the discovery and functional characterization of conserved bacterial toxins with activity against bacteria and fungi.
微生物利用毒素杀死竞争微生物或真核细胞。多态毒素是编码羧基末端毒素结构域的蛋白质。在这里，我们开发了一种计算方法，在 105,438 个微生物基因组中识别出以前未被发现的多态毒素保守毒素结构域。我们验证了九种短毒素，发现它们在大肠杆菌或酿酒酵母中异源表达时会导致细胞死亡。我们还发现了五个能中和毒素的同源免疫基因。2.2%的测序细菌编码这些毒素。这些毒素的一个子集对多种致病真菌具有很强的抗真菌活性，但对两种无脊椎动物模式生物或巨噬细胞没有活性。实验验证表明，这些毒素可能以细胞膜或 DNA 为靶标，或抑制细胞分裂。对两种毒素-免疫蛋白复合物的进一步表征和结构分析证实了 DNase 活性。这些发现拓展了我们对参与微生物间竞争的微生物毒素的认识，可能具有临床和生物技术应用潜力。
{"title":"Systematic discovery of antibacterial and antifungal bacterial toxins","authors":"Nimrod Nachmias, Noam Dotan, Marina Campos Rocha, Rina Fraenkel, Katharina Detert, Monika Kluzek, Maor Shalom, Shani Cheskis, Sonu Peedikayil-Kurien, Gilad Meitav, Arbel Rivitz, Naama Shamash-Halevy, Inbar Cahana, Noam Deouell, Jacob Klein, Meital Oren-Suissa, Herbert Schmidt, Neta Schlezinger, Netanel Tzarum, Yaara Oppenheimer-Shaanan, Asaf Levy","doi":"10.1038/s41564-024-01820-9","DOIUrl":"10.1038/s41564-024-01820-9","url":null,"abstract":"Microorganisms use toxins to kill competing microorganisms or eukaryotic cells. Polymorphic toxins are proteins that encode carboxy-terminal toxin domains. Here we developed a computational approach to identify previously undiscovered, conserved toxin domains of polymorphic toxins within 105,438 microbial genomes. We validated nine short toxins, showing that they cause cell death upon heterologous expression in either Escherichia coli or Saccharomyces cerevisiae. Five cognate immunity genes that neutralize the toxins were also discovered. The toxins are encoded by 2.2% of sequenced bacteria. A subset of the toxins exhibited potent antifungal activity against various pathogenic fungi but not against two invertebrate model organisms or macrophages. Experimental validation suggested that these toxins probably target the cell membrane or DNA or inhibit cell division. Further characterization and structural analysis of two toxin–immunity protein complexes confirmed DNase activity. These findings expand our knowledge of microbial toxins involved in inter-microbial competition that may have the potential for clinical and biotechnological applications. Genome sequence mining and computational analyses lead to the discovery and functional characterization of conserved bacterial toxins with activity against bacteria and fungi.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 11","pages":"3041-3058"},"PeriodicalIF":20.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142452602","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 : 2024-10-22DOI: 10.1038/s41564-024-01825-4
Jose Gabriel Nino Barreat, Aris Katzourakis
Integration of viruses into host genomes can give rise to endogenous viral elements (EVEs), which provide insights into viral diversity, host range and evolution. A systematic search for EVEs is becoming computationally challenging given the available genomic data. We used a cloud-computing approach to perform a comprehensive search for EVEs in the kingdoms Shotokuvirae and Orthornavirae across vertebrates. We identified 2,040 EVEs in 295 vertebrate genomes and provide evidence for EVEs belonging to the families Chuviridae, Paramyxoviridae, Nairoviridae and Benyviridae. We also find an EVE from the Hepacivirus genus of flaviviruses with orthology across murine rodents. In addition, our analyses revealed that reptarenaviruses and filoviruses probably acquired their glycoprotein ectodomains three times independently from retroviral elements. Taken together, these findings encourage the addition of 4 virus families and the Hepacivirus genus to the growing virus fossil record of vertebrates, providing key insights into their natural history and evolution. Computational cloud-based screen of vertebrate genomes identifies endogenous viral elements of members of the kingdoms Shotokuvirae and Orthornavirae and informs about evolutionary history of non-retroviral elements.
{"title":"Deep mining reveals the diversity of endogenous viral elements in vertebrate genomes","authors":"Jose Gabriel Nino Barreat, Aris Katzourakis","doi":"10.1038/s41564-024-01825-4","DOIUrl":"10.1038/s41564-024-01825-4","url":null,"abstract":"Integration of viruses into host genomes can give rise to endogenous viral elements (EVEs), which provide insights into viral diversity, host range and evolution. A systematic search for EVEs is becoming computationally challenging given the available genomic data. We used a cloud-computing approach to perform a comprehensive search for EVEs in the kingdoms Shotokuvirae and Orthornavirae across vertebrates. We identified 2,040 EVEs in 295 vertebrate genomes and provide evidence for EVEs belonging to the families Chuviridae, Paramyxoviridae, Nairoviridae and Benyviridae. We also find an EVE from the Hepacivirus genus of flaviviruses with orthology across murine rodents. In addition, our analyses revealed that reptarenaviruses and filoviruses probably acquired their glycoprotein ectodomains three times independently from retroviral elements. Taken together, these findings encourage the addition of 4 virus families and the Hepacivirus genus to the growing virus fossil record of vertebrates, providing key insights into their natural history and evolution. Computational cloud-based screen of vertebrate genomes identifies endogenous viral elements of members of the kingdoms Shotokuvirae and Orthornavirae and informs about evolutionary history of non-retroviral elements.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 11","pages":"3013-3024"},"PeriodicalIF":20.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41564-024-01825-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142452603","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 : 2024-10-18DOI: 10.1038/s41564-024-01824-5
Racheal S. Dube Mandishora, Brittney L. Dickey, Wenyi Fan, Bradley Sirak, Kimberly Isaacs-Soriano, Julie Rathwell, Martha Abrahamsen, Richard R. Reich, Michael J. Schell, Eduardo Lazcano-Ponce, Luisa L. Villa, Anna R. Giuliano
Oral human papillomavirus (HPV) is associated with oropharyngeal cancer (OPC). Although OPC incidence is increasing globally, knowledge of oral HPV infection rates is limited. Here we carried out an observational epidemiological analysis of oral HPV incidence in 3,137 men enrolled from the United States, Mexico and Brazil between 2005 and 2009. Individuals were followed for new HPV infection for a median of 57 months. Cumulative incidence and factors associated with acquisition were also assessed. The incidence rate of oral oncogenic HPV was 2.4 per 1,000 person-months, did not vary with age and was constant throughout the study period. Risk of oral HPV acquisition was significantly associated with alcohol consumption, having male sexual partners, more lifetime female sexual partners, more oral sex given and higher educational attainment. These data indicate that men are at risk of acquiring oral HPV throughout their lifetime, suggesting that catch-up vaccination may reduce new infection incidence. Multinational analysis of oral human papillomavirus infection incidence and associated factors in 3,137 men reveals infection risk is maintained throughout lifetime, with implications for vaccination strategies.
{"title":"Multinational epidemiological analysis of oral human papillomavirus incidence in 3,137 men","authors":"Racheal S. Dube Mandishora, Brittney L. Dickey, Wenyi Fan, Bradley Sirak, Kimberly Isaacs-Soriano, Julie Rathwell, Martha Abrahamsen, Richard R. Reich, Michael J. Schell, Eduardo Lazcano-Ponce, Luisa L. Villa, Anna R. Giuliano","doi":"10.1038/s41564-024-01824-5","DOIUrl":"10.1038/s41564-024-01824-5","url":null,"abstract":"Oral human papillomavirus (HPV) is associated with oropharyngeal cancer (OPC). Although OPC incidence is increasing globally, knowledge of oral HPV infection rates is limited. Here we carried out an observational epidemiological analysis of oral HPV incidence in 3,137 men enrolled from the United States, Mexico and Brazil between 2005 and 2009. Individuals were followed for new HPV infection for a median of 57 months. Cumulative incidence and factors associated with acquisition were also assessed. The incidence rate of oral oncogenic HPV was 2.4 per 1,000 person-months, did not vary with age and was constant throughout the study period. Risk of oral HPV acquisition was significantly associated with alcohol consumption, having male sexual partners, more lifetime female sexual partners, more oral sex given and higher educational attainment. These data indicate that men are at risk of acquiring oral HPV throughout their lifetime, suggesting that catch-up vaccination may reduce new infection incidence. Multinational analysis of oral human papillomavirus infection incidence and associated factors in 3,137 men reveals infection risk is maintained throughout lifetime, with implications for vaccination strategies.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 11","pages":"2836-2846"},"PeriodicalIF":20.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142448345","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}
Enteroviruses contain multiple serotypes and can cause severe neurological complications. The intricate life cycle of enteroviruses involving dynamic virus–receptor interaction hampers the development of broad therapeutics and vaccines. Here, using function-based screening, we identify a broadly therapeutic antibody h1A6.2 that potently protects mice in lethal models of infection with both enterovirus A71 and coxsackievirus A16 through multiple mechanisms, including inhibition of the virion–SCARB2 interactions and monocyte/macrophage-dependent Fc effector functions. h1A6.2 mitigates inflammation and improves intramuscular mechanics, which are associated with diminished innate immune signalling and preserved tissue repair. Moreover, cryogenic electron microscopy structures delineate an adaptive binding of h1A6.2 to the flexible and dynamic nature of the VP2 EF loop with a binding angle mimicking the SCARB2 receptor. The coordinated binding mode results in efficient binding of h1A6.2 to all viral particle types and facilitates broad neutralization of enterovirus, therefore informing a promising target for the structure-guided design of pan-enterovirus vaccine. Identification of a broadly therapeutic antibody h1A6.2 against enteroviruses, which mimics the entry receptor SCARB2 and triggers monocyte/macrophage-dependent Fc effector functions in mice.
肠道病毒包含多种血清型，可引起严重的神经系统并发症。肠道病毒的生命周期错综复杂，涉及病毒与受体的动态相互作用，这阻碍了广泛疗法和疫苗的开发。在这里，我们通过基于功能的筛选，发现了一种具有广泛治疗作用的抗体 h1A6.2，它能通过多种机制（包括抑制病毒-SCARB2 相互作用和单核细胞/巨噬细胞依赖性 Fc 效应器功能）有效保护感染肠道病毒 A71 和柯萨奇病毒 A16 的致死模型小鼠。此外，低温电子显微镜结构显示，h1A6.2 与 VP2 EF 环的柔性和动态性质进行了适应性结合，其结合角度模仿 SCARB2 受体。这种协调的结合模式使 h1A6.2 与所有病毒颗粒类型有效结合，促进了对肠道病毒的广泛中和，从而为以结构为导向设计泛肠道病毒疫苗提供了一个有前途的靶点。
{"title":"Broadly therapeutic antibody provides cross-serotype protection against enteroviruses via Fc effector functions and by mimicking SCARB2","authors":"Rui Zhu, Yuanyuan Wu, Yang Huang, Yanan Jiang, Yichao Jiang, Dongqing Zhang, Hui Sun, Zhenhong Zhou, Lizhi Zhou, Shihan Weng, Hao Chen, Xiaoqing Chen, Wenjing Ning, Yuxiang Zou, Maozhou He, Hongwei Yang, Weixi Deng, Yu Li, Zhenqin Chen, Xiangzhong Ye, Jinle Han, Zhichao Yin, Huan Zhao, Che Liu, Yuqiong Que, Mujin Fang, Hai Yu, Jun Zhang, Wenxin Luo, Shaowei Li, Qingbing Zheng, Longfa Xu, Ningshao Xia, Tong Cheng","doi":"10.1038/s41564-024-01822-7","DOIUrl":"10.1038/s41564-024-01822-7","url":null,"abstract":"Enteroviruses contain multiple serotypes and can cause severe neurological complications. The intricate life cycle of enteroviruses involving dynamic virus–receptor interaction hampers the development of broad therapeutics and vaccines. Here, using function-based screening, we identify a broadly therapeutic antibody h1A6.2 that potently protects mice in lethal models of infection with both enterovirus A71 and coxsackievirus A16 through multiple mechanisms, including inhibition of the virion–SCARB2 interactions and monocyte/macrophage-dependent Fc effector functions. h1A6.2 mitigates inflammation and improves intramuscular mechanics, which are associated with diminished innate immune signalling and preserved tissue repair. Moreover, cryogenic electron microscopy structures delineate an adaptive binding of h1A6.2 to the flexible and dynamic nature of the VP2 EF loop with a binding angle mimicking the SCARB2 receptor. The coordinated binding mode results in efficient binding of h1A6.2 to all viral particle types and facilitates broad neutralization of enterovirus, therefore informing a promising target for the structure-guided design of pan-enterovirus vaccine. Identification of a broadly therapeutic antibody h1A6.2 against enteroviruses, which mimics the entry receptor SCARB2 and triggers monocyte/macrophage-dependent Fc effector functions in mice.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 11","pages":"2939-2953"},"PeriodicalIF":20.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142448358","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 : 2024-10-18DOI: 10.1038/s41564-024-01834-3
We show that men from the USA, Mexico and Brazil are at risk of acquiring oral human papillomavirus (HPV) throughout their lifetime. Risk factors for new HPV infections are alcohol consumption, having male sexual partners, more lifetime female sexual partners, more oral sex given and higher educational attainment.
{"title":"Factors associated with oral HPV infection among a large multinational cohort of men","authors":"","doi":"10.1038/s41564-024-01834-3","DOIUrl":"10.1038/s41564-024-01834-3","url":null,"abstract":"We show that men from the USA, Mexico and Brazil are at risk of acquiring oral human papillomavirus (HPV) throughout their lifetime. Risk factors for new HPV infections are alcohol consumption, having male sexual partners, more lifetime female sexual partners, more oral sex given and higher educational attainment.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 11","pages":"2801-2802"},"PeriodicalIF":20.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142448325","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 : 2024-10-16DOI: 10.1038/s41564-024-01848-x
Marya Getchell, Suci Wulandari, Ruklanthi de Alwis, Shreya Agoramurthy, Yoong Khean Khoo, Tze-Minn Mak, La Moe, Anne-Claire Stona, Junxiong Pang, Muhd Haziq Fikry Haji Abdul Momin, Afreenish Amir, Lucia Rizka Andalucia, Ghows Azzam, Savuth Chin, Thanat Chookajorn, Govindakarnavar Arunkumar, Do Thai Hung, Aamer Ikram, Runa Jha, Erik A. Karlsson, Mai Quynh Le Thi, Surakameth Mahasirimongkol, Gathsaurie Neelika Malavige, Jessica E. Manning, Syarifah Liza Munira, Nguyen Vu Trung, Imran Nisar, Firdausi Qadri, Farah Naz Qamar, Matthew T. Robinson, Cynthia P. Saloma, Swe Setk, Tahmina Shirin, Le Van Tan, Timothy John R. Dizon, Ravindran Thayan, Hlaing Myat Thu, Hasitha Tissera, Phonepadith Xangsayarath, Zainun Zaini, John C. W. Lim, Sebastian Maurer-Stroh, Gavin J. D. Smith, Lin-Fa Wang, Paul Pronyk
Correction to: Nature Microbiology https://doi.org/10.1038/s41564-024-01809-4, published online 24 September 2024.
{"title":"Author Correction: Pathogen genomic surveillance status among lower resource settings in Asia","authors":"Marya Getchell, Suci Wulandari, Ruklanthi de Alwis, Shreya Agoramurthy, Yoong Khean Khoo, Tze-Minn Mak, La Moe, Anne-Claire Stona, Junxiong Pang, Muhd Haziq Fikry Haji Abdul Momin, Afreenish Amir, Lucia Rizka Andalucia, Ghows Azzam, Savuth Chin, Thanat Chookajorn, Govindakarnavar Arunkumar, Do Thai Hung, Aamer Ikram, Runa Jha, Erik A. Karlsson, Mai Quynh Le Thi, Surakameth Mahasirimongkol, Gathsaurie Neelika Malavige, Jessica E. Manning, Syarifah Liza Munira, Nguyen Vu Trung, Imran Nisar, Firdausi Qadri, Farah Naz Qamar, Matthew T. Robinson, Cynthia P. Saloma, Swe Setk, Tahmina Shirin, Le Van Tan, Timothy John R. Dizon, Ravindran Thayan, Hlaing Myat Thu, Hasitha Tissera, Phonepadith Xangsayarath, Zainun Zaini, John C. W. Lim, Sebastian Maurer-Stroh, Gavin J. D. Smith, Lin-Fa Wang, Paul Pronyk","doi":"10.1038/s41564-024-01848-x","DOIUrl":"https://doi.org/10.1038/s41564-024-01848-x","url":null,"abstract":"<p>Correction to: <i>Nature Microbiology</i> https://doi.org/10.1038/s41564-024-01809-4, published online 24 September 2024.</p>","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"230 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439716","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 : 2024-10-16DOI: 10.1038/s41564-024-01823-6
Yutao Liu, Jialin Wu, Ruiying Liu, Fan Li, Leyan Xuan, Qian Wang, Dan Li, XinTong Chen, Hao Sun, Xiaoya Li, Chen Jin, Di Huang, Linxing Li, Guosheng Tang, Bin Liu
Vibrio cholerae causes cholera, an important cause of death worldwide. A fuller understanding of how virulence is regulated offers the potential for developing virulence inhibitors, regarded as efficient therapeutic alternatives for cholera treatment. Here we show using competitive infections of wild-type and mutant bacteria that the regulator of chitosan utilization, ChsR, increases V. cholerae virulence in vivo. Mechanistically, RNA sequencing, chromatin immunoprecipitation with sequencing and molecular biology approaches revealed that ChsR directly upregulated the expression of the virulence regulator, TcpP, which promoted expression of the cholera toxin and the toxin co-regulated pilus, in response to low O2 levels in the small intestine. We also found that chitosan degradation products inhibit the ChsR–tcpP promoter interaction. Consistently, administration of chitosan oligosaccharide, particularly when delivered via sodium alginate microsphere carriers, reduced V. cholerae intestinal colonization and disease severity in mice by blocking the chsR-mediated pathway. These data reveal the potential of chitosan oligosaccharide as supplemental therapy for cholera treatment and prevention. The chitosan utilization regulator, ChsR, positively regulates Vibrio cholerae virulence factor expression, which can be inhibited therapeutically by chitosan oligosaccharide administration in mice.
{"title":"Vibrio cholerae virulence is blocked by chitosan oligosaccharide-mediated inhibition of ChsR activity","authors":"Yutao Liu, Jialin Wu, Ruiying Liu, Fan Li, Leyan Xuan, Qian Wang, Dan Li, XinTong Chen, Hao Sun, Xiaoya Li, Chen Jin, Di Huang, Linxing Li, Guosheng Tang, Bin Liu","doi":"10.1038/s41564-024-01823-6","DOIUrl":"10.1038/s41564-024-01823-6","url":null,"abstract":"Vibrio cholerae causes cholera, an important cause of death worldwide. A fuller understanding of how virulence is regulated offers the potential for developing virulence inhibitors, regarded as efficient therapeutic alternatives for cholera treatment. Here we show using competitive infections of wild-type and mutant bacteria that the regulator of chitosan utilization, ChsR, increases V. cholerae virulence in vivo. Mechanistically, RNA sequencing, chromatin immunoprecipitation with sequencing and molecular biology approaches revealed that ChsR directly upregulated the expression of the virulence regulator, TcpP, which promoted expression of the cholera toxin and the toxin co-regulated pilus, in response to low O2 levels in the small intestine. We also found that chitosan degradation products inhibit the ChsR–tcpP promoter interaction. Consistently, administration of chitosan oligosaccharide, particularly when delivered via sodium alginate microsphere carriers, reduced V. cholerae intestinal colonization and disease severity in mice by blocking the chsR-mediated pathway. These data reveal the potential of chitosan oligosaccharide as supplemental therapy for cholera treatment and prevention. The chitosan utilization regulator, ChsR, positively regulates Vibrio cholerae virulence factor expression, which can be inhibited therapeutically by chitosan oligosaccharide administration in mice.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"9 11","pages":"2909-2922"},"PeriodicalIF":20.5,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Author Correction: Murine parainfluenza virus persists in lung innate immune cells sustaining chronic lung pathology","authors":"Ítalo Araújo Castro, Yanling Yang, Victoria Gnazzo, Do-Hyun Kim, Steven J. Van Dyken, Carolina B. López","doi":"10.1038/s41564-024-01852-1","DOIUrl":"https://doi.org/10.1038/s41564-024-01852-1","url":null,"abstract":"<p>Correction to: <i>Nature Microbiology</i> https://doi.org/10.1038/s41564-024-01805-8, published online 2 October 2024.</p>","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"1 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142440576","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 : 2024-10-14DOI: 10.1038/s41564-024-01830-7
Arturo Vera-Ponce de León, Tim Hensen, Matthias Hoetzinger, Shashank Gupta, Bronson Weston, Sander M. Johnsen, Jacob A. Rasmussen, Cecilie Grønlund Clausen, Louisa Pless, Ana Raquel Andrade Veríssimo, Knut Rudi, Lars Snipen, Christian René Karlsen, Morten T. Limborg, Stefan Bertilsson, Ines Thiele, Torgeir R. Hvidsten, Simen R. Sandve, Phillip B. Pope, Sabina Leanti La Rosa
To ensure sustainable aquaculture, it is essential to understand the path ‘from feed to fish’, whereby the gut microbiome plays an important role in digestion and metabolism, ultimately influencing host health and growth. Previous work has reported the taxonomic composition of the Atlantic salmon (Salmo salar) gut microbiome; however, functional insights are lacking. Here we present the Salmon Microbial Genome Atlas consisting of 211 high-quality bacterial genomes, recovered by cultivation (n = 131) and gut metagenomics (n = 80) from wild and farmed fish both in freshwater and seawater. Bacterial genomes were taxonomically assigned to 14 different orders, including 35 distinctive genera and 29 previously undescribed species. Using metatranscriptomics, we functionally characterized key bacterial populations, across five phyla, in the salmon gut. This included the ability to degrade diet-derived fibres and release vitamins and other exometabolites with known beneficial effects, which was supported by genome-scale metabolic modelling and in vitro cultivation of selected bacterial species coupled with untargeted metabolomic studies. Together, the Salmon Microbial Genome Atlas provides a genomic and functional resource to enable future studies on salmon nutrition and health. Using shotgun metagenomics, cultivation and metabolic modelling, the authors construct the Salmon Microbial Genome Atlas as a resource for future studies on sustainable aquaculture.
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