Pub Date : 2024-09-11DOI: 10.1038/s41522-024-00550-4
Tianyuan Jia, Xianbiao Bi, Menglu Li, Chenhui Zhang, Anmin Ren, Shangru Li, Tian Zhou, Yingdan Zhang, Yang Liu, Xue Liu, Yinyue Deng, Bin Liu, Guobao Li, Liang Yang
Pseudomonas aeruginosa is a widespread nosocomial pathogen with a significant to cause both severe planktonic acute and biofilm-related chronic infections. Small RNAs (sRNAs) are noncoding regulatory molecules that are stabilized by the RNA chaperone Hfq to trigger various virulence-related signaling pathways. Here, we identified an Hfq-binding sRNA in P. aeruginosa PAO1, PqsS, which promotes bacterial pathogenicity and pseudomonas quinolone signal quorum sensing (pqs QS) system. Specifically, PqsS enhanced acute bacterial infections by inducing host cell death and promoting rhamnolipid-regulated swarming motility. Meanwhile, PqsS reduced chronic infection traits including biofilm formation and antibiotic resistance. Moreover, PqsS repressed pqsL transcript, increasing PQS levels for pqs QS. A PQS-rich environment promoted PqsS expression, thus forming a positive feedback loop. Furthermore, we demonstrated that the PqsS interacts and destabilizes the pqsL mRNA by recruiting RNase E to drive degradation. These findings provide insights for future research on P. aeruginosa pathogenesis and targeted treatment.
{"title":"Hfq-binding small RNA PqsS regulates Pseudomonas aeruginosa pqs quorum sensing system and virulence","authors":"Tianyuan Jia, Xianbiao Bi, Menglu Li, Chenhui Zhang, Anmin Ren, Shangru Li, Tian Zhou, Yingdan Zhang, Yang Liu, Xue Liu, Yinyue Deng, Bin Liu, Guobao Li, Liang Yang","doi":"10.1038/s41522-024-00550-4","DOIUrl":"https://doi.org/10.1038/s41522-024-00550-4","url":null,"abstract":"<p><i>Pseudomonas aeruginosa</i> is a widespread nosocomial pathogen with a significant to cause both severe planktonic acute and biofilm-related chronic infections. Small RNAs (sRNAs) are noncoding regulatory molecules that are stabilized by the RNA chaperone Hfq to trigger various virulence-related signaling pathways. Here, we identified an Hfq-binding sRNA in <i>P. aeruginosa</i> PAO1, PqsS, which promotes bacterial pathogenicity and <i>pseudomonas quinolone signal</i> quorum sensing (<i>pqs</i> QS) system. Specifically, PqsS enhanced acute bacterial infections by inducing host cell death and promoting rhamnolipid-regulated swarming motility. Meanwhile, PqsS reduced chronic infection traits including biofilm formation and antibiotic resistance. Moreover, PqsS repressed <i>pqsL</i> transcript, increasing PQS levels for <i>pqs</i> QS. A PQS-rich environment promoted PqsS expression, thus forming a positive feedback loop. Furthermore, we demonstrated that the PqsS interacts and destabilizes the <i>pqsL</i> mRNA by recruiting RNase E to drive degradation. These findings provide insights for future research on <i>P. aeruginosa</i> pathogenesis and targeted treatment.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142226935","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 : 2024-09-08DOI: 10.1038/s41522-024-00561-1
Sunjae Lee, Victoria Meslier, Gholamreza Bidkhori, Fernando Garcia-Guevara, Lucie Etienne-Mesmin, Frederick Clasen, Junseok Park, Florian Plaza Oñate, Haizhuang Cai, Emmanuelle Le Chatelier, Nicolas Pons, Marcela Pereira, Maike Seifert, Fredrik Boulund, Lars Engstrand, Doheon Lee, Gordon Proctor, Adil Mardinoglu, Stéphanie Blanquet-Diot, David Moyes, Mathieu Almeida, S Dusko Ehrlich, Mathias Uhlen, Saeed Shoaie
Species composition of the healthy adult gut microbiota tends to be stable over time. Destabilization of the gut microbiome under the influence of different factors is the main driver of the microbial dysbiosis and subsequent impacts on host physiology. Here, we used metagenomics data from a Swedish longitudinal cohort, to determine the stability of the gut microbiome and uncovered two distinct microbial species groups; persistent colonizing species (PCS) and transient colonizing species (TCS). We validated the continuation of this grouping, generating gut metagenomics data for additional time points from the same Swedish cohort. We evaluated the existence of PCS/TCS across different geographical regions and observed they are globally conserved features. To characterize PCS/TCS phenotypes, we performed bioreactor fermentation with faecal samples and metabolic modeling. Finally, using chronic disease gut metagenome and other multi-omics data, we identified roles of TCS in microbial dysbiosis and link with abnormal changes to host physiology.
{"title":"Transient colonizing microbes promote gut dysbiosis and functional impairment.","authors":"Sunjae Lee, Victoria Meslier, Gholamreza Bidkhori, Fernando Garcia-Guevara, Lucie Etienne-Mesmin, Frederick Clasen, Junseok Park, Florian Plaza Oñate, Haizhuang Cai, Emmanuelle Le Chatelier, Nicolas Pons, Marcela Pereira, Maike Seifert, Fredrik Boulund, Lars Engstrand, Doheon Lee, Gordon Proctor, Adil Mardinoglu, Stéphanie Blanquet-Diot, David Moyes, Mathieu Almeida, S Dusko Ehrlich, Mathias Uhlen, Saeed Shoaie","doi":"10.1038/s41522-024-00561-1","DOIUrl":"10.1038/s41522-024-00561-1","url":null,"abstract":"<p><p>Species composition of the healthy adult gut microbiota tends to be stable over time. Destabilization of the gut microbiome under the influence of different factors is the main driver of the microbial dysbiosis and subsequent impacts on host physiology. Here, we used metagenomics data from a Swedish longitudinal cohort, to determine the stability of the gut microbiome and uncovered two distinct microbial species groups; persistent colonizing species (PCS) and transient colonizing species (TCS). We validated the continuation of this grouping, generating gut metagenomics data for additional time points from the same Swedish cohort. We evaluated the existence of PCS/TCS across different geographical regions and observed they are globally conserved features. To characterize PCS/TCS phenotypes, we performed bioreactor fermentation with faecal samples and metabolic modeling. Finally, using chronic disease gut metagenome and other multi-omics data, we identified roles of TCS in microbial dysbiosis and link with abnormal changes to host physiology.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11381545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154717","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 : 2024-09-03DOI: 10.1038/s41522-024-00547-z
Anthony M Bonacolta, Pieter T Visscher, Javier Del Campo, Richard Allen White Iii
Protists are less studied for their role and diversity in ecosystems. Notably, protists have played and still play an important role in microbialites. Microbialites, or lithified microbial mats, represent the oldest evidence of fossil biofilms (~3.5 Gyr). Modern microbialites may offer a unique proxy to study the potential role of protists within a geological context. We examined protist diversity in freshwater (Kelly and Pavilion Lake in British Columbia, Canada) and marine (Highborne Cay, Bahamas) to hypersaline (Shark Bay, Australia) microbialites to decipher their geomicrobiological role. The freshwater microbialite communities were clearly distinct from their marine and hypersaline counterparts. Chlorophytes had higher numerical abundance in freshwater microbialites; whereas pennate diatoms dominated numerically in marine microbialites. Despite the differences, protists across ecosystems may have adopted similar roles and functions. We suggest a consistent biogeochemical role of protists across microbialites globally; but that salinity may shape protist composition and evolution in these ecosystems.
{"title":"The eukaryome of modern microbialites reveals distinct colonization across aquatic ecosystems.","authors":"Anthony M Bonacolta, Pieter T Visscher, Javier Del Campo, Richard Allen White Iii","doi":"10.1038/s41522-024-00547-z","DOIUrl":"10.1038/s41522-024-00547-z","url":null,"abstract":"<p><p>Protists are less studied for their role and diversity in ecosystems. Notably, protists have played and still play an important role in microbialites. Microbialites, or lithified microbial mats, represent the oldest evidence of fossil biofilms (~3.5 Gyr). Modern microbialites may offer a unique proxy to study the potential role of protists within a geological context. We examined protist diversity in freshwater (Kelly and Pavilion Lake in British Columbia, Canada) and marine (Highborne Cay, Bahamas) to hypersaline (Shark Bay, Australia) microbialites to decipher their geomicrobiological role. The freshwater microbialite communities were clearly distinct from their marine and hypersaline counterparts. Chlorophytes had higher numerical abundance in freshwater microbialites; whereas pennate diatoms dominated numerically in marine microbialites. Despite the differences, protists across ecosystems may have adopted similar roles and functions. We suggest a consistent biogeochemical role of protists across microbialites globally; but that salinity may shape protist composition and evolution in these ecosystems.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11372052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126194","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 : 2024-09-03DOI: 10.1038/s41522-024-00558-w
Daniel N Villageliu, Kelly C Cunningham, Deandra R Smith, Daren L Knoell, Mason Mandolfo, Todd A Wyatt, Derrick R Samuelson
Alcohol use is an independent risk factor for the development of bacterial pneumonia due, in part, to impaired mucus-facilitated clearance, macrophage phagocytosis, and recruitment of neutrophils. Alcohol consumption is also known to reduce peripheral natural killer (NK) cell numbers and compromise NK cell cytolytic activity, especially NK cells with a mature phenotype. However, the role of innate lymphocytes, such as NK cells during host defense against alcohol-associated bacterial pneumonia is essentially unknown. We have previously shown that indole supplementation mitigates increases in pulmonary bacterial burden and improves pulmonary NK cell recruitment in alcohol-fed mice, which were dependent on aryl hydrocarbon receptor (AhR) signaling. Employing a binge-on-chronic alcohol-feeding model we sought to define the role and interaction of indole and NK cells during pulmonary host defense against alcohol-associated pneumonia. We demonstrate that alcohol dysregulates NK cell effector function and pulmonary recruitment via alterations in two key signaling pathways. We found that alcohol increases transforming growth factor beta (TGF-β) signaling while suppressing AhR signaling. We further demonstrated that NK cells isolated from alcohol-fed mice have a reduced ability to kill Klebsiella pneumoniae. NK cell migratory capacity to chemokines was also significantly altered by alcohol, as NK cells isolated from alcohol-fed mice exhibited preferential migration in response to CXCR3 chemokines but exhibited reduced migration in response to CCR2, CXCR4, and CX3CR1 chemokines. Together this data suggests that alcohol disrupts NK cell-specific TGF-β and AhR signaling pathways leading to decreased pulmonary recruitment and cytolytic activity thereby increasing susceptibility to alcohol-associated bacterial pneumonia.
酗酒是细菌性肺炎发病的一个独立危险因素,部分原因是粘液促进的清除能力、巨噬细胞吞噬能力和中性粒细胞招募能力受损。众所周知,饮酒也会减少外周自然杀伤(NK)细胞的数量,损害 NK 细胞的细胞溶解活性,尤其是具有成熟表型的 NK 细胞。然而,先天性淋巴细胞(如 NK 细胞)在宿主防御酒精相关细菌性肺炎过程中所起的作用基本上是未知的。我们之前已经证明,补充吲哚可以减轻酒精喂养小鼠肺部细菌负荷的增加,并改善肺部 NK 细胞的招募,而这依赖于芳基烃受体(AhR)信号传导。我们采用了一种长期酗酒模型,试图明确吲哚和 NK 细胞在肺部宿主防御酒精相关肺炎过程中的作用和相互作用。我们证明,酒精会通过改变两个关键信号通路来失调 NK 细胞效应功能和肺部招募。我们发现酒精增加了转化生长因子β(TGF-β)信号传导,同时抑制了AhR信号传导。我们进一步证实,从酒精喂养的小鼠体内分离出的 NK 细胞杀死肺炎克雷伯氏菌的能力下降。酒精还显著改变了NK细胞对趋化因子的迁移能力,因为从酒精喂养的小鼠体内分离出的NK细胞对CXCR3趋化因子表现出优先迁移,但对CCR2、CXCR4和CX3CR1趋化因子的迁移能力则有所下降。这些数据共同表明,酒精会破坏 NK 细胞特异性的 TGF-β 和 AhR 信号通路,导致肺募集和细胞溶解活性降低,从而增加对酒精相关细菌性肺炎的易感性。
{"title":"Natural killer cell effector function is critical for host defense against alcohol-associated bacterial pneumonia.","authors":"Daniel N Villageliu, Kelly C Cunningham, Deandra R Smith, Daren L Knoell, Mason Mandolfo, Todd A Wyatt, Derrick R Samuelson","doi":"10.1038/s41522-024-00558-w","DOIUrl":"10.1038/s41522-024-00558-w","url":null,"abstract":"<p><p>Alcohol use is an independent risk factor for the development of bacterial pneumonia due, in part, to impaired mucus-facilitated clearance, macrophage phagocytosis, and recruitment of neutrophils. Alcohol consumption is also known to reduce peripheral natural killer (NK) cell numbers and compromise NK cell cytolytic activity, especially NK cells with a mature phenotype. However, the role of innate lymphocytes, such as NK cells during host defense against alcohol-associated bacterial pneumonia is essentially unknown. We have previously shown that indole supplementation mitigates increases in pulmonary bacterial burden and improves pulmonary NK cell recruitment in alcohol-fed mice, which were dependent on aryl hydrocarbon receptor (AhR) signaling. Employing a binge-on-chronic alcohol-feeding model we sought to define the role and interaction of indole and NK cells during pulmonary host defense against alcohol-associated pneumonia. We demonstrate that alcohol dysregulates NK cell effector function and pulmonary recruitment via alterations in two key signaling pathways. We found that alcohol increases transforming growth factor beta (TGF-β) signaling while suppressing AhR signaling. We further demonstrated that NK cells isolated from alcohol-fed mice have a reduced ability to kill Klebsiella pneumoniae. NK cell migratory capacity to chemokines was also significantly altered by alcohol, as NK cells isolated from alcohol-fed mice exhibited preferential migration in response to CXCR3 chemokines but exhibited reduced migration in response to CCR2, CXCR4, and CX3CR1 chemokines. Together this data suggests that alcohol disrupts NK cell-specific TGF-β and AhR signaling pathways leading to decreased pulmonary recruitment and cytolytic activity thereby increasing susceptibility to alcohol-associated bacterial pneumonia.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11372167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126193","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 : 2024-08-29DOI: 10.1038/s41522-024-00545-1
E Gonzalez, M D Lee, B T Tierney, N Lipieta, P Flores, M Mishra, L Beckett, A Finkelstein, A Mo, P Walton, F Karouia, R Barker, R J Jansen, S J Green, S Weging, J Kelliher, N K Singh, D Bezdan, J Galazska, N J B Brereton
The ISS rodent habitat has provided crucial insights into the impact of spaceflight on mammals, inducing symptoms characteristic of liver disease, insulin resistance, osteopenia, and myopathy. Although these physiological responses can involve the microbiome on Earth, host-microbiota interactions during spaceflight are still being elucidated. We explore murine gut microbiota and host gene expression in the colon and liver after 29 and 56 days of spaceflight using multiomics. Metagenomics revealed significant changes in 44 microbiome species, including relative reductions in bile acid and butyrate metabolising bacteria like Extibacter muris and Dysosmobacter welbionis. Functional prediction indicate over-representation of fatty acid and bile acid metabolism, extracellular matrix interactions, and antibiotic resistance genes. Host gene expression described corresponding changes to bile acid and energy metabolism, and immune suppression. These changes imply that interactions at the host-gut microbiome interface contribute to spaceflight pathology and that these interactions might critically influence human health and long-duration spaceflight feasibility.
{"title":"Spaceflight alters host-gut microbiota interactions.","authors":"E Gonzalez, M D Lee, B T Tierney, N Lipieta, P Flores, M Mishra, L Beckett, A Finkelstein, A Mo, P Walton, F Karouia, R Barker, R J Jansen, S J Green, S Weging, J Kelliher, N K Singh, D Bezdan, J Galazska, N J B Brereton","doi":"10.1038/s41522-024-00545-1","DOIUrl":"https://doi.org/10.1038/s41522-024-00545-1","url":null,"abstract":"<p><p>The ISS rodent habitat has provided crucial insights into the impact of spaceflight on mammals, inducing symptoms characteristic of liver disease, insulin resistance, osteopenia, and myopathy. Although these physiological responses can involve the microbiome on Earth, host-microbiota interactions during spaceflight are still being elucidated. We explore murine gut microbiota and host gene expression in the colon and liver after 29 and 56 days of spaceflight using multiomics. Metagenomics revealed significant changes in 44 microbiome species, including relative reductions in bile acid and butyrate metabolising bacteria like Extibacter muris and Dysosmobacter welbionis. Functional prediction indicate over-representation of fatty acid and bile acid metabolism, extracellular matrix interactions, and antibiotic resistance genes. Host gene expression described corresponding changes to bile acid and energy metabolism, and immune suppression. These changes imply that interactions at the host-gut microbiome interface contribute to spaceflight pathology and that these interactions might critically influence human health and long-duration spaceflight feasibility.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11362537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142109985","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 : 2024-08-29DOI: 10.1038/s41522-024-00542-4
Philipp Licht, Nazzareno Dominelli, Johannes Kleemann, Stefan Pastore, Elena-Sophia Müller, Maximilian Haist, Kim Sophie Hartmann, Henner Stege, Matthias Bros, Markus Meissner, Stephan Grabbe, Ralf Heermann, Volker Mailänder
Mycosis fungoides (MF) is the most common entity of Cutaneous T cell lymphomas (CTCL) and is characterized by the presence of clonal malignant T cells in the skin. The role of the skin microbiome for MF development and progression are currently poorly understood. Using shotgun metagenomic profiling, real-time qPCR, and T cell receptor sequencing, we compared lesional and nonlesional skin of 20 MF patients with early and advanced MF. Additionally, we isolated Staphylococcus aureus and other bacteria from MF skin for functional profiling and to study the S. aureus virulence factor spa. We identified a subgroup of MF patients with substantial dysbiosis on MF lesions and concomitant outgrowth of S. aureus on plaque-staged lesions, while the other MF patients had a balanced microbiome on lesional skin. Dysbiosis and S. aureus outgrowth were accompanied by ectopic levels of cutaneous antimicrobial peptides (AMPs), including adaptation of the plaque-derived S. aureus strain. Furthermore, the plaque-derived S. aureus strain showed a reduced susceptibility towards antibiotics and an upregulation of the virulence factor spa, which may activate the NF-κB pathway. Remarkably, patients with dysbiosis on MF lesions had a restricted T cell receptor repertoire and significantly lower event-free survival. Our study highlights the potential for microbiome-modulating treatments targeting S. aureus to prevent MF progression.
真菌病(MF)是皮肤 T 细胞淋巴瘤(CTCL)中最常见的一种,其特点是皮肤中存在克隆性恶性 T 细胞。目前,人们对皮肤微生物组在 MF 发生和发展过程中的作用还知之甚少。我们使用枪式元基因组剖析、实时 qPCR 和 T 细胞受体测序技术,比较了 20 名早期和晚期 MF 患者的病变和非病变皮肤。此外,我们还从 MF 皮肤中分离出了金黄色葡萄球菌和其他细菌,以进行功能分析并研究金黄色葡萄球菌的毒力因子 spa。我们发现有一部分手足口病患者的皮损处存在严重的菌群失调,斑块期皮损处同时有金黄色葡萄球菌生长,而其他手足口病患者的皮损处微生物群平衡。菌群失调和金黄色葡萄球菌生长伴随着皮肤抗菌肽(AMPs)水平的异位,包括斑块衍生的金黄色葡萄球菌菌株的适应。此外,菌斑衍生的金黄色葡萄球菌菌株对抗生素的敏感性降低,毒力因子 spa 上调,这可能会激活 NF-κB 通路。值得注意的是,中耳炎病变上菌群失调的患者T细胞受体谱系受限,无事件生存率明显降低。我们的研究强调了针对金黄色葡萄球菌的微生物组调节疗法在预防 MF 进展方面的潜力。
{"title":"The skin microbiome stratifies patients with cutaneous T cell lymphoma and determines event-free survival.","authors":"Philipp Licht, Nazzareno Dominelli, Johannes Kleemann, Stefan Pastore, Elena-Sophia Müller, Maximilian Haist, Kim Sophie Hartmann, Henner Stege, Matthias Bros, Markus Meissner, Stephan Grabbe, Ralf Heermann, Volker Mailänder","doi":"10.1038/s41522-024-00542-4","DOIUrl":"https://doi.org/10.1038/s41522-024-00542-4","url":null,"abstract":"<p><p>Mycosis fungoides (MF) is the most common entity of Cutaneous T cell lymphomas (CTCL) and is characterized by the presence of clonal malignant T cells in the skin. The role of the skin microbiome for MF development and progression are currently poorly understood. Using shotgun metagenomic profiling, real-time qPCR, and T cell receptor sequencing, we compared lesional and nonlesional skin of 20 MF patients with early and advanced MF. Additionally, we isolated Staphylococcus aureus and other bacteria from MF skin for functional profiling and to study the S. aureus virulence factor spa. We identified a subgroup of MF patients with substantial dysbiosis on MF lesions and concomitant outgrowth of S. aureus on plaque-staged lesions, while the other MF patients had a balanced microbiome on lesional skin. Dysbiosis and S. aureus outgrowth were accompanied by ectopic levels of cutaneous antimicrobial peptides (AMPs), including adaptation of the plaque-derived S. aureus strain. Furthermore, the plaque-derived S. aureus strain showed a reduced susceptibility towards antibiotics and an upregulation of the virulence factor spa, which may activate the NF-κB pathway. Remarkably, patients with dysbiosis on MF lesions had a restricted T cell receptor repertoire and significantly lower event-free survival. Our study highlights the potential for microbiome-modulating treatments targeting S. aureus to prevent MF progression.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11358159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142093647","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 : 2024-08-29DOI: 10.1038/s41522-024-00556-y
Adam M Hamilton, Lisa Blackmer-Raynolds, Yaqing Li, Sean D Kelly, Nardos Kebede, Anna E Williams, Jianjun Chang, Sandra M Garraway, Shanthi Srinivasan, Timothy R Sampson
Spinal cord injury (SCI) results in numerous systemic dysfunctions, including intestinal dysmotility and enteric nervous system (ENS) atrophy. The ENS has capacity to recover following perturbation, yet intestinal pathologies persist. With emerging evidence demonstrating SCI-induced alterations to gut microbiome composition, we hypothesized that microbiome modulation contributes to post-injury enteric recovery. Here, we show that intervention with the dietary fiber, inulin, prevents SCI-induced ENS atrophy and dysmotility in mice. While SCI-associated microbiomes and specific injury-sensitive gut microbes are not sufficient to modulate intestinal dysmotility after injury, intervention with microbially-derived short-chain fatty acid (SCFA) metabolites prevents ENS dysfunctions in injured mice. Notably, inulin-mediated resilience is dependent on IL-10 signaling, highlighting a critical diet-microbiome-immune axis that promotes ENS resilience post-injury. Overall, we demonstrate that diet and microbially-derived signals distinctly impact ENS survival after traumatic spinal injury and represent a foundation to uncover etiological mechanisms and future therapeutics for SCI-induced neurogenic bowel.
{"title":"Diet-microbiome interactions promote enteric nervous system resilience following spinal cord injury.","authors":"Adam M Hamilton, Lisa Blackmer-Raynolds, Yaqing Li, Sean D Kelly, Nardos Kebede, Anna E Williams, Jianjun Chang, Sandra M Garraway, Shanthi Srinivasan, Timothy R Sampson","doi":"10.1038/s41522-024-00556-y","DOIUrl":"10.1038/s41522-024-00556-y","url":null,"abstract":"<p><p>Spinal cord injury (SCI) results in numerous systemic dysfunctions, including intestinal dysmotility and enteric nervous system (ENS) atrophy. The ENS has capacity to recover following perturbation, yet intestinal pathologies persist. With emerging evidence demonstrating SCI-induced alterations to gut microbiome composition, we hypothesized that microbiome modulation contributes to post-injury enteric recovery. Here, we show that intervention with the dietary fiber, inulin, prevents SCI-induced ENS atrophy and dysmotility in mice. While SCI-associated microbiomes and specific injury-sensitive gut microbes are not sufficient to modulate intestinal dysmotility after injury, intervention with microbially-derived short-chain fatty acid (SCFA) metabolites prevents ENS dysfunctions in injured mice. Notably, inulin-mediated resilience is dependent on IL-10 signaling, highlighting a critical diet-microbiome-immune axis that promotes ENS resilience post-injury. Overall, we demonstrate that diet and microbially-derived signals distinctly impact ENS survival after traumatic spinal injury and represent a foundation to uncover etiological mechanisms and future therapeutics for SCI-induced neurogenic bowel.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11362535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142109983","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 : 2024-08-29DOI: 10.1038/s41522-024-00552-2
Baixing Chen, Luis Ponce Benavente, Marco Chittò, Virginia Post, Caroline Constant, Stephan Zeiter, Pamela Nylund, Matteo D'Este, Mercedes González Moreno, Andrej Trampuz, Jeroen Wagemans, Rob Lavigne, Jolien Onsea, R Geoff Richards, Willem-Jan Metsemakers, T Fintan Moriarty
Fracture-related infections (FRIs), particularly those caused by methicillin-resistant Staphylococcus aureus (MRSA), are challenging to treat. This study designed and evaluated a hydrogel loaded with a cocktail of bacteriophages and vancomycin (1.2 mg/mL). The co-delivery hydrogel showed 99.72% reduction in MRSA biofilm in vitro. The hydrogel released 54% of phages and 82% of vancomycin within 72 h and maintained activity for eight days, in vivo the co-delivery hydrogel with systemic antibiotic significantly reduced bacterial load by 0.99 log10 CFU compared to controls, with active phages detected in tissues at euthanasia (2 × 103 PFU/mL). No phage resistance was detected in the phage treatment groups, and serum neutralization resulted in only a 20% reduction in phage count. In this work, we show that a phage-antibiotic co-delivery system via CMC hydrogel is a promising adjunct to systemic antibiotic therapy for MRSA-induced FRI, highlighting its potential for localized, sustained delivery and improved treatment outcomes.
{"title":"Combination of bacteriophages and vancomycin in a co-delivery hydrogel for localized treatment of fracture-related infections.","authors":"Baixing Chen, Luis Ponce Benavente, Marco Chittò, Virginia Post, Caroline Constant, Stephan Zeiter, Pamela Nylund, Matteo D'Este, Mercedes González Moreno, Andrej Trampuz, Jeroen Wagemans, Rob Lavigne, Jolien Onsea, R Geoff Richards, Willem-Jan Metsemakers, T Fintan Moriarty","doi":"10.1038/s41522-024-00552-2","DOIUrl":"https://doi.org/10.1038/s41522-024-00552-2","url":null,"abstract":"<p><p>Fracture-related infections (FRIs), particularly those caused by methicillin-resistant Staphylococcus aureus (MRSA), are challenging to treat. This study designed and evaluated a hydrogel loaded with a cocktail of bacteriophages and vancomycin (1.2 mg/mL). The co-delivery hydrogel showed 99.72% reduction in MRSA biofilm in vitro. The hydrogel released 54% of phages and 82% of vancomycin within 72 h and maintained activity for eight days, in vivo the co-delivery hydrogel with systemic antibiotic significantly reduced bacterial load by 0.99 log10 CFU compared to controls, with active phages detected in tissues at euthanasia (2 × 10<sup>3</sup> PFU/mL). No phage resistance was detected in the phage treatment groups, and serum neutralization resulted in only a 20% reduction in phage count. In this work, we show that a phage-antibiotic co-delivery system via CMC hydrogel is a promising adjunct to systemic antibiotic therapy for MRSA-induced FRI, highlighting its potential for localized, sustained delivery and improved treatment outcomes.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11362333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142109982","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}
The pig gut virome plays a vital role in the gut microbial ecosystem of pigs. However, a comprehensive understanding of their diversity and a reference database for the virome are currently lacking. To address this gap, we established a Pig Virome Database (PVD) that comprised of 5,566,804 viral contig sequences from 4650 publicly available gut metagenomic samples using a pipeline designated "metav". By clustering sequences, we identified 48,299 viral operational taxonomic units (vOTUs) genomes of at least medium quality, of which 92.83% of which were not found in existing major databases. The majority of vOTUs were identified as Caudoviricetes (72.21%). The PVD database contained a total of 2,362,631 protein-coding genes across the above medium-quality vOTUs genomes that can be used to explore the functional potential of the pig gut virome. These findings highlight the extensive diversity of viruses in the pig gut and provide a pivotal reference dataset for forthcoming research concerning the pig gut virome.
{"title":"Massive expansion of the pig gut virome based on global metagenomic mining.","authors":"Jiandui Mi, Xiaoping Jing, Chouxian Ma, Yiwen Yang, Yong Li, Yu Zhang, Ruijun Long, Haixue Zheng","doi":"10.1038/s41522-024-00554-0","DOIUrl":"https://doi.org/10.1038/s41522-024-00554-0","url":null,"abstract":"<p><p>The pig gut virome plays a vital role in the gut microbial ecosystem of pigs. However, a comprehensive understanding of their diversity and a reference database for the virome are currently lacking. To address this gap, we established a Pig Virome Database (PVD) that comprised of 5,566,804 viral contig sequences from 4650 publicly available gut metagenomic samples using a pipeline designated \"metav\". By clustering sequences, we identified 48,299 viral operational taxonomic units (vOTUs) genomes of at least medium quality, of which 92.83% of which were not found in existing major databases. The majority of vOTUs were identified as Caudoviricetes (72.21%). The PVD database contained a total of 2,362,631 protein-coding genes across the above medium-quality vOTUs genomes that can be used to explore the functional potential of the pig gut virome. These findings highlight the extensive diversity of viruses in the pig gut and provide a pivotal reference dataset for forthcoming research concerning the pig gut virome.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11362615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142109984","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 : 2024-08-28DOI: 10.1038/s41522-024-00549-x
Anna K Hartikainen, Jonna Jalanka, Perttu Lahtinen, Alise J Ponsero, Tuomas Mertsalmi, Laura Finnegan, Fiona Crispie, Paul D Cotter, Perttu Arkkila, Reetta Satokari
Imbalanced microbiota may contribute to the pathophysiology of irritable bowel syndrome (IBS), thus fecal microbiota transplantation (FMT) has been suggested as a potential treatment. Previous studies on the relationship between clinical improvement and microbiota after FMT have been inconclusive. In this study, we used 16S rRNA gene amplicon and shotgun metagenomics data from a randomized, placebo controlled FMT trial on 49 IBS patients to analyze changes after FMT in microbiota composition and its functional potential, and to identify connections between microbiota and patients' clinical outcome. As a result, we found that the successful modulation of microbiota composition and functional profiles by FMT from a healthy donor was not associated with the resolution of symptoms in IBS patients. Notably, a donor derived strain of Prevotella copri dominated the microbiota in those patients in the FMT group who had a low relative abundance of P. copri pre-FMT. The results highlight the multifactorial nature of IBS and the role of recipient's microbiota in the colonization of donor's strains.
{"title":"Fecal microbiota transplantation influences microbiota without connection to symptom relief in irritable bowel syndrome patients.","authors":"Anna K Hartikainen, Jonna Jalanka, Perttu Lahtinen, Alise J Ponsero, Tuomas Mertsalmi, Laura Finnegan, Fiona Crispie, Paul D Cotter, Perttu Arkkila, Reetta Satokari","doi":"10.1038/s41522-024-00549-x","DOIUrl":"10.1038/s41522-024-00549-x","url":null,"abstract":"<p><p>Imbalanced microbiota may contribute to the pathophysiology of irritable bowel syndrome (IBS), thus fecal microbiota transplantation (FMT) has been suggested as a potential treatment. Previous studies on the relationship between clinical improvement and microbiota after FMT have been inconclusive. In this study, we used 16S rRNA gene amplicon and shotgun metagenomics data from a randomized, placebo controlled FMT trial on 49 IBS patients to analyze changes after FMT in microbiota composition and its functional potential, and to identify connections between microbiota and patients' clinical outcome. As a result, we found that the successful modulation of microbiota composition and functional profiles by FMT from a healthy donor was not associated with the resolution of symptoms in IBS patients. Notably, a donor derived strain of Prevotella copri dominated the microbiota in those patients in the FMT group who had a low relative abundance of P. copri pre-FMT. The results highlight the multifactorial nature of IBS and the role of recipient's microbiota in the colonization of donor's strains.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11349920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142081148","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}