The Staphylococcus aureus (S. aureus) SaeRS two-component system (TCS) regulates over 20 virulence factors. While its impact on chronic infection has been thoroughly discussed, its role in the early stage of infection remains elusive. Since macrophages serve as the primary immune defenders at the onset of infection, this study investigates the influence of SaeRS on macrophage functions and elucidates the underlying mechanisms. Macrophage expression of inflammatory and chemotactic factors, phagocytosis, and bactericidal activity against S. aureus were assessed, along with the evaluation of cellular oxidative stress. SaeRS was found to impair macrophage function. Mechanistically, SaeRS inhibited NF-κB pathway activation via toll-like receptor 2 (TLR2). Its immune-modulating effect could partially be explained by the strengthened biofilm formation. More importantly, we found SaeRS compromised macrophage immune functions at early infection stages even prior to biofilm formation. These early immune evasion effects were dependent on bacterial clumping as cytokine secretion, phagocytosis, and bactericidal activity were repaired when clumping was inhibited. We speculate that the bacterial clumping-mediated antigen mask is responsible for SaeRS-mediated immune evasion at the early infection stage. In vivo, ΔsaeRS infection was cleared earlier, accompanied by early pro-inflammatory cytokines production, and increased tissue oxidative stress. Subsequently, macrophages transitioned to an anti-inflammatory state, thereby promoting tissue repair. In summary, our findings underscore the critical role of the SaeRS TCS in S. aureus pathogenicity, particularly during early infection, which is likely initiated by SaeRS-mediated bacterial clumping.
{"title":"Staphylococcus aureus SaeRS impairs macrophage immune functions through bacterial clumps formation in the early stage of infection.","authors":"Mingzhang Li, Boyong Wang, Jiani Chen, Luhui Jiang, Yawen Zhou, Geyong Guo, Feng Jiang, Yujie Hu, Changming Wang, Yi Yang, Jin Tang, Pei Han, Jinlong Yu, Hao Shen","doi":"10.1038/s41522-024-00576-8","DOIUrl":"10.1038/s41522-024-00576-8","url":null,"abstract":"<p><p>The Staphylococcus aureus (S. aureus) SaeRS two-component system (TCS) regulates over 20 virulence factors. While its impact on chronic infection has been thoroughly discussed, its role in the early stage of infection remains elusive. Since macrophages serve as the primary immune defenders at the onset of infection, this study investigates the influence of SaeRS on macrophage functions and elucidates the underlying mechanisms. Macrophage expression of inflammatory and chemotactic factors, phagocytosis, and bactericidal activity against S. aureus were assessed, along with the evaluation of cellular oxidative stress. SaeRS was found to impair macrophage function. Mechanistically, SaeRS inhibited NF-κB pathway activation via toll-like receptor 2 (TLR2). Its immune-modulating effect could partially be explained by the strengthened biofilm formation. More importantly, we found SaeRS compromised macrophage immune functions at early infection stages even prior to biofilm formation. These early immune evasion effects were dependent on bacterial clumping as cytokine secretion, phagocytosis, and bactericidal activity were repaired when clumping was inhibited. We speculate that the bacterial clumping-mediated antigen mask is responsible for SaeRS-mediated immune evasion at the early infection stage. In vivo, ΔsaeRS infection was cleared earlier, accompanied by early pro-inflammatory cytokines production, and increased tissue oxidative stress. Subsequently, macrophages transitioned to an anti-inflammatory state, thereby promoting tissue repair. In summary, our findings underscore the critical role of the SaeRS TCS in S. aureus pathogenicity, particularly during early infection, which is likely initiated by SaeRS-mediated bacterial clumping.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11456606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381355","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 : 2024-10-04DOI: 10.1038/s41522-024-00574-w
Satoshi Kawaichi, Rhitu Kotoky, Jacek Fiutowski, Amelia-Elena Rotaru
Due to unique genomic adaptations, Methanococcus maripaludis Mic1c10 is highly corrosive when in direct contact with Fe0. A critical adaptation involves increased glycosylation of an extracellular [NiFe]-hydrogenase, facilitating its anchoring to cell surface proteins. Corrosive strains adapt to the constructed environment via horizontal gene transfer while retaining ancestral genes important for intraspecies competition and surface attachment. This calls for a reevaluation of how the built environment impacts methane cycling.
{"title":"Adaptation of a methanogen to Fe<sup>0</sup> corrosion via direct contact.","authors":"Satoshi Kawaichi, Rhitu Kotoky, Jacek Fiutowski, Amelia-Elena Rotaru","doi":"10.1038/s41522-024-00574-w","DOIUrl":"10.1038/s41522-024-00574-w","url":null,"abstract":"<p><p>Due to unique genomic adaptations, Methanococcus maripaludis Mic1c10 is highly corrosive when in direct contact with Fe<sup>0</sup>. A critical adaptation involves increased glycosylation of an extracellular [NiFe]-hydrogenase, facilitating its anchoring to cell surface proteins. Corrosive strains adapt to the constructed environment via horizontal gene transfer while retaining ancestral genes important for intraspecies competition and surface attachment. This calls for a reevaluation of how the built environment impacts methane cycling.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11452385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375766","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 : 2024-10-02DOI: 10.1038/s41522-024-00555-z
Iztok Dogsa, Barbara Bellich, Mojca Blaznik, Cristina Lagatolla, Neil Ravenscroft, Roberto Rizzo, David Stopar, Paola Cescutti
Extracellular polysaccharides are crucial components for biofilm development. Although Bacillus subtilis is one of the most characterized Gram-positive biofilm model system, the structure-function of its exopolysaccharide, EpsA-O, remains to be elucidated. By combining chemical analysis, NMR spectroscopy, rheology, and molecular modeling, high-resolution data of EpsA-O structure from atom to supramolecular scale was obtained. The repeating unit is composed of the trisaccharide backbone [→3)-β-D-QuipNAc4NAc-(1→3)-β-D-GalpNAc-(1→3)-α-D-GlcpNAc-(1]n, and the side chain β-D-Galp(3,4-S-Pyr)-(1→6)-β-D-Galp(3,4-S-Pyr)-(1→6)-α-D-Galp-(1→ linked to C4 of GalNAc. Close agreement between the primary structure and rheological behavior allowed us to model EpsA-O macromolecular and supramolecular solution structure, which can span the intercellular space forming a gel that leads to a complex 3D biofilm network as corroborated by a mutant strain with impaired ability to produce EpsA-O. This is a comprehensive structure-function investigation of the essential biofilm adhesive exopolysaccharide that will serve as a useful guide for future studies in biofilm architecture formation.
{"title":"Bacillus subtilis EpsA-O: A novel exopolysaccharide structure acting as an efficient adhesive in biofilms.","authors":"Iztok Dogsa, Barbara Bellich, Mojca Blaznik, Cristina Lagatolla, Neil Ravenscroft, Roberto Rizzo, David Stopar, Paola Cescutti","doi":"10.1038/s41522-024-00555-z","DOIUrl":"10.1038/s41522-024-00555-z","url":null,"abstract":"<p><p>Extracellular polysaccharides are crucial components for biofilm development. Although Bacillus subtilis is one of the most characterized Gram-positive biofilm model system, the structure-function of its exopolysaccharide, EpsA-O, remains to be elucidated. By combining chemical analysis, NMR spectroscopy, rheology, and molecular modeling, high-resolution data of EpsA-O structure from atom to supramolecular scale was obtained. The repeating unit is composed of the trisaccharide backbone [→3)-β-D-QuipNAc4NAc-(1→3)-β-D-GalpNAc-(1→3)-α-D-GlcpNAc-(1]<sub>n</sub>, and the side chain β-D-Galp(3,4-S-Pyr)-(1→6)-β-D-Galp(3,4-S-Pyr)-(1→6)-α-D-Galp-(1→ linked to C4 of GalNAc. Close agreement between the primary structure and rheological behavior allowed us to model EpsA-O macromolecular and supramolecular solution structure, which can span the intercellular space forming a gel that leads to a complex 3D biofilm network as corroborated by a mutant strain with impaired ability to produce EpsA-O. This is a comprehensive structure-function investigation of the essential biofilm adhesive exopolysaccharide that will serve as a useful guide for future studies in biofilm architecture formation.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365959","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 : 2024-10-02DOI: 10.1038/s41522-024-00536-2
Sunil Nagpal, Sarvesh Kumar Srivastava
Ingestible microdevices represent a breakthrough in non-invasive sampling of the human gastrointestinal (GI) tract. By capturing the native spatiotemporal microbiome and intricate biochemical gradients, these devices allow a non-invasive multi-omic access to the unperturbed host-microbiota crosstalk, immune/nutritional landscapes and gut-organ connections. We present the current progress of GI sampling microdevices towards personalized metabolism and fostering collaboration among clinicians, engineers, and data scientists.
{"title":"Colon or semicolon: gut sampling microdevices for omics insights.","authors":"Sunil Nagpal, Sarvesh Kumar Srivastava","doi":"10.1038/s41522-024-00536-2","DOIUrl":"10.1038/s41522-024-00536-2","url":null,"abstract":"<p><p>Ingestible microdevices represent a breakthrough in non-invasive sampling of the human gastrointestinal (GI) tract. By capturing the native spatiotemporal microbiome and intricate biochemical gradients, these devices allow a non-invasive multi-omic access to the unperturbed host-microbiota crosstalk, immune/nutritional landscapes and gut-organ connections. We present the current progress of GI sampling microdevices towards personalized metabolism and fostering collaboration among clinicians, engineers, and data scientists.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365960","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 : 2024-10-02DOI: 10.1038/s41522-024-00572-y
Amin Valiei, Andrew Dickson, Javad Aminian-Dehkordi, Mohammad R K Mofrad
The gut microbiome plays a major role in human health; however, little is known about the structural arrangement of microbes and factors governing their distribution. In this work, we present an in silico agent-based model (ABM) to conceptually simulate the dynamics of gut mucosal bacterial communities. We explored how various types of metabolic interactions, including competition, neutralism, commensalism, and mutualism, affect community structure, through nutrient consumption and metabolite exchange. Results showed that, across scenarios with different initial species abundances, cross-feeding promotes species coexistence. Morphologically, competition and neutralism resulted in segregation, while mutualism and commensalism fostered high intermixing. In addition, cooperative relations resulted in community properties with little sensitivity to the selective uptake of metabolites produced by the host. Moreover, metabolic interactions strongly influenced colonization success following the invasion of newcomer species. These results provide important insights into the utility of ABM in deciphering complex microbiome patterns.
{"title":"Metabolic interactions shape emergent biofilm structures in a conceptual model of gut mucosal bacterial communities.","authors":"Amin Valiei, Andrew Dickson, Javad Aminian-Dehkordi, Mohammad R K Mofrad","doi":"10.1038/s41522-024-00572-y","DOIUrl":"10.1038/s41522-024-00572-y","url":null,"abstract":"<p><p>The gut microbiome plays a major role in human health; however, little is known about the structural arrangement of microbes and factors governing their distribution. In this work, we present an in silico agent-based model (ABM) to conceptually simulate the dynamics of gut mucosal bacterial communities. We explored how various types of metabolic interactions, including competition, neutralism, commensalism, and mutualism, affect community structure, through nutrient consumption and metabolite exchange. Results showed that, across scenarios with different initial species abundances, cross-feeding promotes species coexistence. Morphologically, competition and neutralism resulted in segregation, while mutualism and commensalism fostered high intermixing. In addition, cooperative relations resulted in community properties with little sensitivity to the selective uptake of metabolites produced by the host. Moreover, metabolic interactions strongly influenced colonization success following the invasion of newcomer species. These results provide important insights into the utility of ABM in deciphering complex microbiome patterns.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365961","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 : 2024-10-01DOI: 10.1038/s41522-024-00567-9
Wen Sun, Yue Zhang, Ruochun Guo, Shanshan Sha, Changming Chen, Hayan Ullah, Yan Zhang, Jie Ma, Wei You, Jinxin Meng, Qingbo Lv, Lin Cheng, Shao Fan, Rui Li, Xiaohong Mu, Shenghui Li, Qiulong Yan
The gut microbiome has been implicated in various human diseases, though findings across studies have shown considerable variability. In this study, we reanalyzed 6314 publicly available fecal metagenomes from 36 case-control studies on different diseases to investigate microbial diversity and disease-shared signatures. Using a unified analysis pipeline, we observed reduced microbial diversity in many diseases, while some exhibited increased diversity. Significant alterations in microbial communities were detected across most diseases. A meta-analysis identified 277 disease-associated gut species, including numerous opportunistic pathogens enriched in patients and a depletion of beneficial microbes. A random forest classifier based on these signatures achieved high accuracy in distinguishing diseased individuals from controls (AUC = 0.776) and high-risk patients from controls (AUC = 0.825), and it also performed well in external cohorts. These results offer insights into the gut microbiome's role in common diseases in the Chinese population and will guide personalized disease management strategies.
{"title":"A population-scale analysis of 36 gut microbiome studies reveals universal species signatures for common diseases.","authors":"Wen Sun, Yue Zhang, Ruochun Guo, Shanshan Sha, Changming Chen, Hayan Ullah, Yan Zhang, Jie Ma, Wei You, Jinxin Meng, Qingbo Lv, Lin Cheng, Shao Fan, Rui Li, Xiaohong Mu, Shenghui Li, Qiulong Yan","doi":"10.1038/s41522-024-00567-9","DOIUrl":"10.1038/s41522-024-00567-9","url":null,"abstract":"<p><p>The gut microbiome has been implicated in various human diseases, though findings across studies have shown considerable variability. In this study, we reanalyzed 6314 publicly available fecal metagenomes from 36 case-control studies on different diseases to investigate microbial diversity and disease-shared signatures. Using a unified analysis pipeline, we observed reduced microbial diversity in many diseases, while some exhibited increased diversity. Significant alterations in microbial communities were detected across most diseases. A meta-analysis identified 277 disease-associated gut species, including numerous opportunistic pathogens enriched in patients and a depletion of beneficial microbes. A random forest classifier based on these signatures achieved high accuracy in distinguishing diseased individuals from controls (AUC = 0.776) and high-risk patients from controls (AUC = 0.825), and it also performed well in external cohorts. These results offer insights into the gut microbiome's role in common diseases in the Chinese population and will guide personalized disease management strategies.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11442664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351060","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 : 2024-09-30DOI: 10.1038/s41522-024-00560-2
P J Alexander, L B Oyama, H Olleik, F Godoy Santos, S O'Brien, A Cookson, S A Cochrane, B F Gilmore, M Maresca, S A Huws
Acinetobacter baumannii is designated by the World Health Organisation as a critical priority pathogen. Previously we discovered antimicrobial peptides (AMPs), namely Lynronne-1, -2 and -3, with efficacy against bacterial pathogens, such as Staphylococcus aureus and Pseudomonas aeruginosa. Here we assessed Lynronne-1, -2 and -3 structure by circular dichroism and efficacy against clinical strains of A. baumannii. All Lynronne AMPs demonstrated alpha-helical secondary structures and had antimicrobial activity towards all tested strains of A. baumannii (Minimum Inhibitory Concentrations 2-128 μg/ml), whilst also having anti-biofilm activity. Lynronne-2 and -3 demonstrated additive effects with amoxicillin and erythromycin, and synergy with gentamicin. The AMPs demonstrated little toxicity towards mammalian cell lines or Galleria mellonella. Fluorescence-based assay data demonstrated that Lynronne-1 and -3 had higher membrane-destabilising action against A. baumannii in comparison with Lynronne-2, which was corroborated by transcriptomic analysis. For the first time, we demonstrate the therapeutic activity of Lynronne AMPs against A. baumannii.
{"title":"Microbiome-derived antimicrobial peptides show therapeutic activity against the critically important priority pathogen, Acinetobacter baumannii.","authors":"P J Alexander, L B Oyama, H Olleik, F Godoy Santos, S O'Brien, A Cookson, S A Cochrane, B F Gilmore, M Maresca, S A Huws","doi":"10.1038/s41522-024-00560-2","DOIUrl":"10.1038/s41522-024-00560-2","url":null,"abstract":"<p><p>Acinetobacter baumannii is designated by the World Health Organisation as a critical priority pathogen. Previously we discovered antimicrobial peptides (AMPs), namely Lynronne-1, -2 and -3, with efficacy against bacterial pathogens, such as Staphylococcus aureus and Pseudomonas aeruginosa. Here we assessed Lynronne-1, -2 and -3 structure by circular dichroism and efficacy against clinical strains of A. baumannii. All Lynronne AMPs demonstrated alpha-helical secondary structures and had antimicrobial activity towards all tested strains of A. baumannii (Minimum Inhibitory Concentrations 2-128 μg/ml), whilst also having anti-biofilm activity. Lynronne-2 and -3 demonstrated additive effects with amoxicillin and erythromycin, and synergy with gentamicin. The AMPs demonstrated little toxicity towards mammalian cell lines or Galleria mellonella. Fluorescence-based assay data demonstrated that Lynronne-1 and -3 had higher membrane-destabilising action against A. baumannii in comparison with Lynronne-2, which was corroborated by transcriptomic analysis. For the first time, we demonstrate the therapeutic activity of Lynronne AMPs against A. baumannii.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11443000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351064","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 adhesion of bacteria to surfaces is associated with physicochemical and biological interactions. The present investigations provide new results about the differential adhesion levels of skin bacteria using a representative 3D skin model which mainly relies on the different physicochemical properties of the respective surfaces. Modulation of the adhesion of bacteria and thus their colonization, may occur by adjusting the physicochemical properties of the epidermal and bacterial surfaces. Lewis acid and hydrophobicity were the most strongly correlated parameters with the antiadhesion properties of the tested compounds. Modulation of physicochemical properties appears to be the primary driver of reduced Staphylococcus aureus adhesion in this study, with no significant changes observed in the expression of genes associated with classical adhesion pathways.
{"title":"Preventing bacterial adhesion to skin by altering their physicochemical cell surface properties specifically.","authors":"Xavier Janvier, Severine Jansen, Charleyne Prenom, Nabiha Khodabux, Francesca Zuttion, Cécile Duclairoir-Poc, Sylvie Cupferman, Ahmad Khodr","doi":"10.1038/s41522-024-00568-8","DOIUrl":"10.1038/s41522-024-00568-8","url":null,"abstract":"<p><p>The adhesion of bacteria to surfaces is associated with physicochemical and biological interactions. The present investigations provide new results about the differential adhesion levels of skin bacteria using a representative 3D skin model which mainly relies on the different physicochemical properties of the respective surfaces. Modulation of the adhesion of bacteria and thus their colonization, may occur by adjusting the physicochemical properties of the epidermal and bacterial surfaces. Lewis acid and hydrophobicity were the most strongly correlated parameters with the antiadhesion properties of the tested compounds. Modulation of physicochemical properties appears to be the primary driver of reduced Staphylococcus aureus adhesion in this study, with no significant changes observed in the expression of genes associated with classical adhesion pathways.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11442763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351065","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}
Stress can lead to gut dysbiosis in brain-gut axis disordered diseases as irritable bowel syndrome (IBS), yet the mechanisms how stress transfer from the brain to the gut and disrupt gut microbiota remain elusive. Here we describe a stress-responsive brain-to-gut axis which impairs colonocytes' mitochondria to trigger gut dysbiosis. Patients with IBS exhibit significantly increased facultative anaerobes and decreased obligate anaerobes, related to increased serum corticotropin-releasing hormone (CRH) level and defected colonocytes' mitochondria ultrastructure. Mice exposed to acute stress experienced enhanced CRH-CRH receptor type 1 (CRHR1) signaling, which impaired mitochondria and epithelium hypoxia in the colon, subsequently triggered gut dysbiosis. Antagonizing CRHR1 expression to inhibit cAMP/Ras/MAPK signaling or activating mitochondria respiration conferred resilience against stress-induced mitochondria damaging and epithelium hypoxia impairment, ultimately improving gut dysbiosis. These results suggest that the CRH-CRHR1-mitochondria pathway plays a pivotal role in stress-induced gut dysbiosis that could be therapeutically targeted for stress-induced gastrointestinal diseases. Yiming Zhang et.al report that psychological stress activated Corticotropin-releasing hormone (CRH)-CRH receptor type 1 (CRHR1)-mitochondria pathway to trigger gut dysbiosis and reveal CRHR1 upregulation damages mitochondria via cAMP/Ras/MAPK signaling in colonocytes.
{"title":"Stress triggers gut dysbiosis via CRH-CRHR1-mitochondria pathway.","authors":"Yiming Zhang, Xiaoang Li, Siqi Lu, Huaizhu Guo, Zhuangyi Zhang, Haonan Zheng, Cunzheng Zhang, Jindong Zhang, Kun Wang, Fei Pei, Liping Duan","doi":"10.1038/s41522-024-00571-z","DOIUrl":"10.1038/s41522-024-00571-z","url":null,"abstract":"<p><p>Stress can lead to gut dysbiosis in brain-gut axis disordered diseases as irritable bowel syndrome (IBS), yet the mechanisms how stress transfer from the brain to the gut and disrupt gut microbiota remain elusive. Here we describe a stress-responsive brain-to-gut axis which impairs colonocytes' mitochondria to trigger gut dysbiosis. Patients with IBS exhibit significantly increased facultative anaerobes and decreased obligate anaerobes, related to increased serum corticotropin-releasing hormone (CRH) level and defected colonocytes' mitochondria ultrastructure. Mice exposed to acute stress experienced enhanced CRH-CRH receptor type 1 (CRHR1) signaling, which impaired mitochondria and epithelium hypoxia in the colon, subsequently triggered gut dysbiosis. Antagonizing CRHR1 expression to inhibit cAMP/Ras/MAPK signaling or activating mitochondria respiration conferred resilience against stress-induced mitochondria damaging and epithelium hypoxia impairment, ultimately improving gut dysbiosis. These results suggest that the CRH-CRHR1-mitochondria pathway plays a pivotal role in stress-induced gut dysbiosis that could be therapeutically targeted for stress-induced gastrointestinal diseases. Yiming Zhang et.al report that psychological stress activated Corticotropin-releasing hormone (CRH)-CRH receptor type 1 (CRHR1)-mitochondria pathway to trigger gut dysbiosis and reveal CRHR1 upregulation damages mitochondria via cAMP/Ras/MAPK signaling in colonocytes.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11442948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351066","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 : 2024-09-30DOI: 10.1038/s41522-024-00570-0
Grégoire Davignon, Natalia Pietrosemoli, Nadia Benaroudj, Marie-Estelle Soupé-Gilbert, Julie Cagliero, Élodie Turc, Mathieu Picardeau, Linda Guentas, Cyrille Goarant, Roman Thibeaux
Life-threatening Leptospira interrogans navigate a dual existence: surviving in the environment and infecting mammalian hosts. Biofilm formation is presumably an important survival strategy to achieve this process. Understanding the relation between biofilm and virulence might improve our comprehension of leptospirosis epidemiology. Our study focused on elucidating Leptospira's adaptations and regulations involved in such complex microenvironments. To determine the transcriptional profile of Leptospira in biofilm, we compared the transcriptomes in late biofilms and in exponential planktonic cultures. While genes for motility, energy production, and metabolism were downregulated, those governing general stress response, defense against metal stress, and redox homeostasis showed a significant upsurge, hinting at a tailored defensive strategy against stress. Further, despite a reduced metabolic state, biofilm disruption swiftly restored metabolic activity. Crucially, bacteria in late biofilms or resulting from biofilm disruption retained virulence in an animal model. In summary, our study highlights Leptospira's adaptive equilibrium in biofilms: minimizing energy expenditure, potentially aiding in withstanding stresses while maintaining pathogenicity. These insights are important for explaining the survival strategies of Leptospira, revealing that a biofilm lifestyle may confer an advantage in maintaining virulence, an understanding essential for managing leptospirosis across both environmental and mammalian reservoirs.
{"title":"Leptospira interrogans biofilm transcriptome highlights adaption to starvation and general stress while maintaining virulence.","authors":"Grégoire Davignon, Natalia Pietrosemoli, Nadia Benaroudj, Marie-Estelle Soupé-Gilbert, Julie Cagliero, Élodie Turc, Mathieu Picardeau, Linda Guentas, Cyrille Goarant, Roman Thibeaux","doi":"10.1038/s41522-024-00570-0","DOIUrl":"10.1038/s41522-024-00570-0","url":null,"abstract":"<p><p>Life-threatening Leptospira interrogans navigate a dual existence: surviving in the environment and infecting mammalian hosts. Biofilm formation is presumably an important survival strategy to achieve this process. Understanding the relation between biofilm and virulence might improve our comprehension of leptospirosis epidemiology. Our study focused on elucidating Leptospira's adaptations and regulations involved in such complex microenvironments. To determine the transcriptional profile of Leptospira in biofilm, we compared the transcriptomes in late biofilms and in exponential planktonic cultures. While genes for motility, energy production, and metabolism were downregulated, those governing general stress response, defense against metal stress, and redox homeostasis showed a significant upsurge, hinting at a tailored defensive strategy against stress. Further, despite a reduced metabolic state, biofilm disruption swiftly restored metabolic activity. Crucially, bacteria in late biofilms or resulting from biofilm disruption retained virulence in an animal model. In summary, our study highlights Leptospira's adaptive equilibrium in biofilms: minimizing energy expenditure, potentially aiding in withstanding stresses while maintaining pathogenicity. These insights are important for explaining the survival strategies of Leptospira, revealing that a biofilm lifestyle may confer an advantage in maintaining virulence, an understanding essential for managing leptospirosis across both environmental and mammalian reservoirs.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11442865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351063","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}