mSphere最新文献

{"title":"mSphere of Influence: The perfect slice-from pizza to proteases.","authors":"Nicholas J Lennemann","doi":"10.1128/msphere.00556-25","DOIUrl":"https://doi.org/10.1128/msphere.00556-25","url":null,"abstract":"<p><p>Nick Lennemann studies the intracellular interactions of viral and host proteins. In this mSphere of Influence article, he discusses his employment history and the mentors that promoted his training and transition to an independent research program focused on proteolytic determinants of virus infection. He highlights how \"A novel interaction between dengue virus nonstructural protein 1 and the NS4A-2K-4B precursor is required for viral RNA replication but not for formation of the membranous replication organelle\" by A. Płaszczyca, P. Scaturro, C. J. Neufeldt, M. Cortese, et al. (PLoS Pathog 15:e1007736, 2019, https://doi.org/10.1371/journal.ppat.1007736) and \"Species-specific disruption of STING-dependent antiviral cellular defenses by the Zika virus NS2B3 protease\" by Q. Ding, J. M. Gaska, F. Douam, L. Wei, et al. (Proc Natl Acad Sci USA 115: E6310-E6318, 2018, https://doi.org/10.1073/pnas.1803406115) demonstrate the importance of viral protease activity for the establishment of a productive intracellular environment for infection.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0055625"},"PeriodicalIF":3.1,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145252020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dietary modulation of the rumen microbiome drives the expression of metabolic and methanogenic pathways in <i>Bos indicus</i>.","authors":"Juliana Virginio da Silva, Liliane Costa Conteville, Jennifer Jessica Bruscadin, Tainã Figueiredo Cardoso, Thanny Porto, Priscila Silva Neubern de Oliveira, Adhemar Zerlotini, Sergio Raposo de Medeiros, Gerson Barreto Mourão, Luiz Lehmann Coutinho, Julio Cesar Pascale Palhares, Alexandre Berndt, Le Luo Guan, Bruno Gabriel Nascimento Andrade, Luciana Correia de Almeida Regitano","doi":"10.1128/msphere.00535-25","DOIUrl":"https://doi.org/10.1128/msphere.00535-25","url":null,"abstract":"<p><p>Diet influences ruminal methane emissions by modulating the composition and activity of the rumen microbiome. However, how diet shapes the functional capacity of the rumen microbiome in Nelore cattle (<i>Bos indicus</i>), a key tropical beef breed, remains unclear. This study used metatranscriptomics to investigate how dietary supplementation with agro-industrial by-products affects the active rumen microbiome and its association with residual methane emissions. Rumen samples from 50 Nelore cattle fed either a conventional or by-product-based diet revealed that the active microbiome was dominated by bacteria (88.4% ± 3.16%) and archaea (11.6% ± 3.16%), with no significant taxonomic differences between diets. Despite this, functional profiling identified genes from 193 pathways and 3,512 gene families, with distinct metabolic signatures between diets. Specifically, six pathways and 87 gene families were unique to the conventional diet, while seven pathways and 210 gene families were unique to the by-product diet. The associations between gene families enriched under each diet with residual methane emission revealed that the expression of two gene families exhibited negative correlations, while five were positively correlated with methane emission under conventional diet. In the by-product diet, we identified five gene families positively associated with methane emissions and 14 negatively associated. These results demonstrate that diet alters rumen microbial functions with methane mitigation potential, without affecting taxonomic composition.</p><p><strong>Importance: </strong>Understanding how diet modulates the functional activity of the rumen microbiome is essential for developing strategies to mitigate methane emissions in cattle. This study provides novel insights into how feeding agro-industrial by-products to Nelore cattle (<i>Bos indicus</i>), a key tropical beef breed, reshapes the functional profile of the rumen microbiome. Although no taxonomic shifts were detected, animals fed the by-product diet exhibited a greater number of microbial functions associated with lower methane production potential. These findings suggest that diet-driven modulation of microbial metabolism could contribute to strategies aimed at reducing methane emissions. Moreover, the use of by-products supports circular economy principles, enhancing the sustainability and economic resilience of tropical livestock systems. This work emphasizes the importance of examining the active microbiome through RNA rather than solely profiling taxonomic composition without considering microbial activity. It also contributes to unveiling microbial functions to support future methane mitigation and sustainable feeding strategies.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0053525"},"PeriodicalIF":3.1,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145252025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Candida auris</i> persists in the vaginal microaerobic niche in the absence of interleukin-17A.","authors":"Masahiro Abe, Sota Sadamoto, Akiko Nagamori, Minoru Shinozaki, Sayoko Oiki, Amato Otani, Ami Koizumi, Takayuki Shinohara, Yoichiro Iwakura, Kazutoshi Shibuya, Yoshitsugu Miyazaki","doi":"10.1128/msphere.00446-25","DOIUrl":"https://doi.org/10.1128/msphere.00446-25","url":null,"abstract":"<p><p><i>Candida auris</i> is an emerging fungus notable for its high drug resistance and persistent colonization of human hosts and environmental surfaces. However, its role in vulvovaginal candidiasis (VVC), a common form of superficial candidiasis, remains poorly understood. In this study, we investigated the colonization capacity of <i>C. auris</i> and vaginal defense mechanisms in a VVC model. Using an estrogenized VVC mouse model, we evaluated fungal burden, inflammatory cell counts, and S100A8 concentrations in vaginal lavages of wild-type (WT) and IL-17A knockout (<i>Il17a^-/-</i>) C57BL/6J mice following <i>C. auris</i> inoculation. Histopathological examination and flow cytometry analysis of vaginal immune cells were also conducted. Additionally, an <i>in vitro</i> adhesion assay was performed using VK2/E6E7 vaginal epithelial cells under aerobic and microaerobic conditions mimicking the vaginal environment. Persistent colonization by <i>C. auris,</i> particularly clades I, III, and IV, with minimal infiltration of inflammatory cells, was confirmed in <i>Il17a^-/-</i> mice. These findings were also supported by histopathological analysis. S100A8 concentration analysis revealed significant differences between WT and <i>Il17a^-/-</i> mice, with lower levels detected in the <i>Il17a^-/-</i> group. Furthermore, S100A8 levels showed positive correlations with inflammatory cell count and negative correlations with vaginal fungal burden. Flow cytometry analysis demonstrated a reduced number of vaginal neutrophils in <i>Il17a^-/-</i> mice. Additionally, <i>in vitro</i> adhesion assay revealed increased <i>C. auris</i> adherence to vaginal epithelial cells under microaerobic conditions. <i>C. auris</i> exhibits a strong affinity for the vaginal epithelium, and IL-17A appears to play a protective role in <i>C. auris-</i>associated VVC.</p><p><strong>Importance: </strong><i>Candida auris</i> is an emerging fungal species, and several reports have recently identified C. auris in patients with vulvovaginal candidiasis (VVC), although few studies have investigated the relationship between C. auris and VVC or the associated host factors. Our study, using the VVC mouse model, confirmed persistent vaginal colonization by <i>C. auris</i>, especially clades I, III, and IV, along with reduced neutrophil infiltration and lower S100A8 secretion under interleukin-17A-deficient conditions. In addition, <i>in vitro</i> assays demonstrated enhanced <i>C. auris</i> adhesion to vaginal epithelial cells, especially microaerobic conditions imitating human vaginal microenvironments. Our findings suggest that <i>C. auris</i> exhibits strong vaginal tropism, and IL-17A plays a critical role in controlling <i>C. auris</i>-associated VVC.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0044625"},"PeriodicalIF":3.1,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145252006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GlcNAc induces GlcNAc catabolic genes and inhibits filamentation via YlRep1-YlNgs1 signaling in the dimorphic yeast <i>Yarrowia lipolytica</i>.","authors":"Zhen-Hua Wang, Meng-Yang Xu, Xiang-Dong Gao","doi":"10.1128/msphere.00477-25","DOIUrl":"https://doi.org/10.1128/msphere.00477-25","url":null,"abstract":"<p><p>Many fungal species can utilize <i>N</i>-acetylglucosamine (GlcNAc) as a carbon source. Studies in the pathogenic yeast <i>Candida albicans</i> have revealed that GlcNAc utilization and the induction of GlcNAc catabolic genes depend on the Ndt80 family transcription factor CaRep1 and the histone acetyltransferase CaNgs1. Additionally, GlcNAc induces filamentation via both alkalinization of the medium and CaNgs1 signaling. However, the roles of YlRep1 and YlNgs1 in GlcNAc catabolism and filamentous growth are not clear in the dimorphic yeast <i>Yarrowia lipolytica</i>. In this study, we demonstrate that YlRep1 and YlNgs1 are essential for the induction of GlcNAc catabolic genes in <i>Y. lipolytica</i>, which is similar to the function of CaRep1 and CaNgs1. YlRep1 and YlNgs1 interact physically and exhibit transcriptional activation activity on a reporter gene. Interestingly, unlike in <i>C. albicans</i>, GlcNAc inhibits filamentation in <i>Y. lipolytica</i>. This inhibition requires YlRep1-YlNgs1 but does not depend on the alteration of ambient pH. We show that YlRep1 and YlNgs1 co-repress a set of transcription factor and cell wall protein genes, some of which are associated with filamentation. Notably, this repression is independent of GlcNAc catabolism but requires the GlcNAc kinase, YlNag5.IMPORTANCEGlcNAc has been used previously to induce filamentation in <i>Yarrowia lipolytica</i>, but often in combination with a citrate buffer at near-neutral pH. The exact role of GlcNAc in regulating filamentous growth is unclear. In this study, we report that GlcNAc inhibits rather than promotes filamentation in <i>Y. lipolytica</i>, and this function does not require GlcNAc catabolism or the alteration of ambient pH by GlcNAc catabolism. We show that YlRep1-YlNgs1 signaling, which activates GlcNAc catabolic genes, represses a set of filamentation-related genes and is a key regulator in the inhibition of filamentation by GlcNAc. This finding indicates that YlRep1-YlNgs1 has dual roles, functioning both in the activation of GlcNAc catabolic genes and the repression of filamentation-related genes in response to GlcNAc. These findings provide new insights into the regulatory mechanisms of GlcNAc catabolism and signaling in <i>Y. lipolytica</i>.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0047725"},"PeriodicalIF":3.1,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The resilience of <i>Salmonella</i> to bile stress is impaired due to the reduced efflux pump activity mediated by the antioxidant enzyme YqhD.","authors":"Kirti Parmar, Yogyta Kumari, Raju S Rajmani, Dipshikha Chakravortty","doi":"10.1128/msphere.00382-25","DOIUrl":"https://doi.org/10.1128/msphere.00382-25","url":null,"abstract":"<p><p>Bile salts play a critical role in modulating the host gut. They possess antimicrobial properties wherein they disrupt the bacterial membrane and produce reactive oxygen species (ROS), causing DNA damage. Pathogens like <i>Salmonella</i> regulate their metabolic activity to counteract the effects of bile. This study investigates the role of YqhD, an aldehyde reductase, in <i>Salmonella'</i>s bile salt susceptibility. Our findings reveal increased survival of the <i>yqhD</i> mutant in the <i>in-vitro</i> studies in LB media with bile, liver cell line HepG2 and C57BL/6 mice on treatment with 8% sodium cholate in the cecum. Bile salts, physiologically produced for the digestion of fat, enhanced the organ burden of the <i>yqhD</i> mutant in C57BL/6 mice on replacing the chow diet with a high-fat diet (HFD). The <i>yqhD</i> mutation, on bile salt exposure, also leads to increased ROS levels and modulation of antioxidant genes in the bacteria. The addition of the antioxidant glutathione during bile stress enhances the survival of STM WT and makes it similar to the survival of STM Δ<i>yqhD</i>. Similarly, in the <i>gp91^-/-phox</i> mice, the organ burden and pathology of the liver and spleen were increased on STM WT infection, while it remained similar for the <i>yqhD</i> mutant on exposure to HFD compared to that of chow-fed mice. Furthermore, the <i>yqhD</i> mutant exhibited increased AcrAB efflux pump activity, regulated by RamA/R regulon.</p><p><strong>Importance: </strong>Foodborne pathogen <i>Salmonella</i> can tolerate high concentrations of bile and even survive the harsh environment of the gall bladder. This study is significant as it explores the role of a novel antioxidant gene <i>yqhD</i> in bile salt susceptibility of <i>Salmonella</i> Typhimurium and Typhi. It highlights how the presence of gene <i>yqhD</i>, though advantageous in macrophages, reduces the <i>Salmonella</i> survival on bile salt exposure <i>in vitro</i> and in liver cell line HepG2. Deletion of <i>yqhD</i> increased the survival on bile stress exposure, which was attributed to its ability to induce the AcrAB efflux pump of <i>Salmonella</i>. A deeper understanding of how <i>Salmonella</i> modulates gene expression in response to bile stress could provide valuable insights into addressing the chronic carriage of <i>Salmonella</i>.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0038225"},"PeriodicalIF":3.1,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Viral community diversity in the rhizosphere of the foundation salt marsh plant <i>Spartina alterniflora</i>.","authors":"Isabelle Du Plessis, Hannah Snyder, Rachel Calder, José L Rolando, Joel E Kostka, Joshua S Weitz, Marian Dominguez-Mirazo","doi":"10.1128/msphere.00234-25","DOIUrl":"https://doi.org/10.1128/msphere.00234-25","url":null,"abstract":"<p><p>Viruses of microorganisms impact microbial population dynamics, community structure, nutrient cycling, gene transfer, and genomic innovation. In wetlands, root-associated microbial communities mediate key biogeochemical processes important for plants involved in ecosystem maintenance. Nonetheless, the presence and role of microbial viruses in salt marshes remain poorly understood. In this study, we analyzed 24 metagenomes retrieved from the root zone of <i>Spartina alterniflora</i>, a foundation plant in salt marshes of the eastern and Gulf coasts of the U.S. The samples span three plant compartments-bulk sediment, rhizosphere, and root-and two cordgrass plant phenotypes: short and tall. We observed differentiation between phenotypes and increased similarity in viral communities between the root and rhizosphere, indicating that plant compartment and phenotype shape viral community composition. The majority of viral populations characterized are novel at the genus level, with a subset predicted to target microorganisms known to carry out key biogeochemical functions. The findings contribute to ongoing efforts to understand plant-associated viral diversity and community composition and to identify potential targets for exploring viral modulation of microbially mediated ecosystem functioning in intertidal wetlands.IMPORTANCESalt marshes are vital coastal ecosystems. Microbes in these environments drive nutrient cycling and support plant health, with <i>Spartina alterniflora</i> serving as a foundation species. This study explores viral communities associated with <i>S. alterniflora</i>, revealing how plant compartments and phenotypes shape viral composition. The discovery of numerous novel viruses, some potentially influencing microbes involved in key biogeochemical processes, highlights their ecological significance. Given the increasing pressures on coastal ecosystems, understanding virus-microbe-plant interactions is essential for predicting and managing ecosystem responses to environmental change.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0023425"},"PeriodicalIF":3.1,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences in GenBank and RefSeq annotations may affect genomics data interpretation for <i>Pseudomonas putida</i> KT2440.","authors":"Guilherme Marcelino Viana de Siqueira, Thomas Eng, Aindrila Mukhopadhyay, María-Eugenia Guazzaroni","doi":"10.1128/msphere.00391-25","DOIUrl":"https://doi.org/10.1128/msphere.00391-25","url":null,"abstract":"<p><p>Annotations of genomic features are cornerstone data that support routine workflows in conventional omics analyses in <i>Pseudomonas putida</i> KT2440 and other organisms. The GenBank and the RefSeq versions of the annotated KT2440 genome are two popular resources widely cited in the literature; yet, they originate from distinct prediction pipelines and possess potentially different biological information that is often overlooked. In this study, we systematically compared the features present in these resources and found that approximately 16% of the total of KT2440 open reading frames (ORFs) show differences in their predicted genomic positions across GenBank and RefSeq, despite sharing equivalent locus tag codes. Furthermore, we show that these discrepancies can affect the results of high-throughput analyses by processing a collection of RNAseq expression data sets utilizing both annotations. Our findings provide a comprehensive overview of the current state of available resources for genomics research in <i>P. putida</i> KT2440 and highlight a rarely addressed yet widespread potential pitfall in the literature on this organism, with possible implications for other prokaryotes.IMPORTANCEGenome annotation databases often rely on different statistical models for their function predictions and inherently carry biases propagated into studies using them. This work provides a quantitative assessment of two popular annotation resources for the model bacterium <i>Pseudomonas putida</i> KT2440 and their influence on data interpretation. As large-scale omics data sets are commonly used to inform experimental decisions, our results aim to promote awareness of the caveats associated with these computational resources and foster reproducibility and transparency in <i>P. putida</i> research.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0039125"},"PeriodicalIF":3.1,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antifungal, antibacterial, and anti-inflammatory activity of glycerol dithionomonolaurate, an analog of glycerol monolaurate.","authors":"Patrick M Schlievert, Paul E Brennan, Robert E Klem, Dayton T Reardan","doi":"10.1128/msphere.00318-25","DOIUrl":"https://doi.org/10.1128/msphere.00318-25","url":null,"abstract":"<p><p>Glycerol dithionomonolaurate (NB2) is an analog of the natural antimicrobial compound glycerol monolaurate (GML) with enhanced antimicrobial activity. The advantage of NB2 over GML is the presence of a dithionate to greatly reduce microbial cleavage through glycerol ester hydrolases, such as <i>Staphylococcus aureus</i> lipase. NB2 exhibited antimicrobial activity against <i>Candida</i> fungal species, including <i>Candida auris</i>, with comparable minimum bactericidal concentration (MBC) and minimum inhibitory concentration (MIC) of 50-100 µg/mL compared to 250-500 µg/mL for GML. NB2 exhibited a broad range of antibacterial activity including both gram-positive and gram-negative organisms, while sparing normal microbiome lactobacilli. When 10⁸ <i>C. auris</i> and 10⁹ <i>S. aureus</i> were incubated on Todd Hewitt agar plates in the presence of two times the MBC for NB2, no resistant colonies grew, likely the result of the large number of antimicrobial targets inhibited. Like GML, NB2 inhibited exotoxin production at non-antibacterial concentrations. NB2 exhibited anti-staphylococcal activity when tested topically on a dermatitis skin model on rabbits. NB2 inhibited the production of chemokines (interleukin-8 and macrophage inflammatory protein-3α) by human vaginal epithelial cells, suggesting anti-inflammatory activity. Unlike clear GML solutions, NB2 was pale yellow. The absorption spectrum of NB2 was not sufficient to raise Food and Drug Administration concerns over phototoxicity. Collectively, the data suggest that NB2 could become a useful topical agent for the prevention of both fungal and bacterial infections as a dual-active anti-infective, killing microbes and reducing harmful inflammation, such as seen in atopic dermatitis.</p><p><strong>Importance: </strong>Fungi and many bacteria commonly develop resistance to antimicrobial agents or have inherent resistance. Many microbes initiate infections through the skin and mucous membranes, in part by producing toxins and causing harmful inflammation. We describe a novel topical antimicrobial agent, glycerol dithionomonolaurate (NB2), effective against <i>Candida</i> and a wide range of gram-positive and gram-negative bacteria; the compound did not kill normal microbiome lactobacilli. NB2 is likely to have many microbial targets for killing, suggesting resistance to the molecule may not develop. At sub-antibacterial concentrations, glycerol dithionomonolaurate inhibited exotoxin production by <i>Staphylococcus aureus</i>. The molecule was not inactivated by staphylococcal lipase. Glycerol dithionomonolaurate effectively treated <i>S. aureus</i> dermatitis in a rabbit skin model and reduced chemokine production by human epithelial cells. Glycerol dithionomonolaurate may prove useful to treat many types of skin and mucous membrane infections by both antimicrobial and anti-inflammatory activities, such as in atopic dermatitis.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0031825"},"PeriodicalIF":3.1,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic and metabolomic analysis reveals new insights into quaternary amine metabolism in <i>Citrobacter amalonaticus</i> CJ25.","authors":"Roshan Timsina, Ryan A Gora, Donald J Ferguson","doi":"10.1128/msphere.00421-25","DOIUrl":"10.1128/msphere.00421-25","url":null,"abstract":"<p><p>Gut microbiota and human physiology are closely linked, and our microbiota can influence disease through immunological and metabolic activity. Quaternary amines, such as choline and carnitine, are abundant in the human gut and are found in red meat, beef, eggs, seafood, wheat, and beets. Canonically, choline and carnitine are broken down into the pro-atherogenic metabolite, trimethylamine (TMA), by various microbes in the human gut. A glycyl radical enzyme, CutC, is involved in the breakdown of choline to TMA. Carnitine is broken down to TMA via a gamma-butyrobetaine intermediate. TMA from the human gut increases levels of TMA <i>N</i>-oxide in blood and promotes atherosclerosis. <i>Citrobacter amalonaticus</i> CJ25, a gut strain isolated and characterized in our lab, has been shown to grow on choline or carnitine as the sole carbon-energy source without generating TMA. Because the genome lacks canonical enzymes involved in the degradation of choline and no TMA was produced in both choline and carnitine growth conditions, we analyzed the choline and carnitine metabolism using a combined metabolomic and proteomic approach. CJ25 metabolizes choline and carnitine into glycine betaine (GB) via pathways involving novel enzyme homologs, as indicated by proteomic analysis. The proteomics showed putative dehydrogenases that could be oxidizing choline and carnitine to GB. These non-atherogenic pathways involving novel enzyme homologs that we identify in CJ25 may also exist in other gut microbiota, which could amplify the effects of these pathways significantly, possibly reducing the risk of atherosclerotic cardiovascular disease in individuals harboring these microbiota.IMPORTANCEThe human gut microbiome has been shown to contribute to atherosclerotic cardiovascular disease with adverse health effects throughout the world. Gut microbes canonically metabolize quaternary amines into proatherogenic TMA. In this study, a gut bacterium, CJ25, metabolizes choline and carnitine to a non-atherogenic product, glycine betaine, potentially using novel dehydrogenase homologs for their oxidation. Notably, the ability of CJ25 to metabolize choline and carnitine in a non-atherogenic manner establishes its potential as a beneficial human gut bacterium. Additionally, enzymes identified in CJ25 for choline and carnitine breakdown may be present in other gut microbes, which could amplify the effects of these pathways and reduce the risk of atherosclerotic cardiovascular disease more universally.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0042125"},"PeriodicalIF":3.1,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12482172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144961687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial variation of infectious virus load in aggregated day 3 post-inoculation respiratory tract tissues from influenza A virus-infected ferrets.","authors":"Troy J Kieran, Xiangjie Sun, Terrence M Tumpey, Taronna R Maines, Jessica A Belser","doi":"10.1128/msphere.00346-25","DOIUrl":"10.1128/msphere.00346-25","url":null,"abstract":"<p><p>The ferret model is widely used to study influenza A viruses (IAVs) isolated from multiple avian and mammalian species, as IAVs typically replicate in the respiratory tract of ferrets without the need for prior host adaptation. During standard IAV risk assessments, tissues are routinely collected from ferrets at a fixed time point post-inoculation to assess the capacity for systemic spread. Here, we describe a data set of virus titers in tissues collected from both respiratory tract and extrapulmonary sites 3 days post-inoculation from over 300 ferrets inoculated with more than 100 unique IAVs (inclusive of H1, H2, H3, H5, H7, and H9 IAV subtypes, both mammalian and zoonotic origin). All experiments were conducted by a single research group under a uniform experimental protocol, making it the largest well-controlled publicly available data set to date of discrete tissue titers reported on a per-ferret level. Analysis of these tissues revealed spatial variation in infectious virus load across different tissues, coupled with different interdependence of infectious viral titers throughout the ferret respiratory tract, dependent on the subtype and sequence identity of the IAV. Collectively, this data set enhances our understanding of the diverse heterogeneity exhibited by IAV strains that pose a threat to human health, as observed in tissues collected during the acute phase of infection in mammals, and enables subsequent in-depth analyses spanning a wide array of data science, statistical, and modeling approaches.IMPORTANCEThe three Rs (reduction, refinement, and replacement, which govern ethical and humane use of animals in scientific research) compel investigators to consider ways to maximize value and impact of <i>in vivo</i> experimentation using a minimum number of animals. One way to achieve this is to aggregate and share publicly results from multiple studies for subsequent investigation. This resource report describes such a data set, reporting infectious virus titers detected in multiple tissues from influenza A virus-infected ferrets, day 3 post-inoculation, aggregated from studies conducted over multiple decades by one research group. We provide usage notes for best practices to inform analysis of these data by other investigators and report results of exploratory studies that illustrate conclusions that can be informed by analyses of this nature. Future public release of like data sets by other groups with similar historical archives may be informed by the practices and formatting described herein.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0034625"},"PeriodicalIF":3.1,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12482141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}