mSphere最新文献

{"title":"Alarmone ppGpp modulates bacterial motility, zeamine production, and virulence of <i>Dickeya oryzae</i> through the regulation of and cooperation with the putrescine signaling mechanism.","authors":"Zurong Shi, Zhibin Liang, Qian Yang, Lian-Hui Zhang, Qingwei Wang","doi":"10.1128/msphere.00682-24","DOIUrl":"https://doi.org/10.1128/msphere.00682-24","url":null,"abstract":"<p><p>Putrescine is an important interspecies and interkingdom communication signal, modulating the bacterial motility, biofilm formation, and virulence of <i>D. oryzae</i>. The understanding of the regulation of putrescine biosynthesis and transport in <i>D. oryzae</i> is limited. In this study, we report that alarmone ppGpp hierarchically modulates putrescine biosynthesis and transport and synergistically cooperates with putrescine to regulate virulence traits and the virulence of <i>D. oryzae</i>. We found that the alarmone ppGpp synthesized by RelA regulated putrescine biosynthesis through modulating <i>speA</i> expression, and the product putrescine would thus inhibit the expression of <i>potF</i> and <i>plaP</i>. Remarkably, we unveiled the synergistic effect of alarmone ppGpp and putrescine on the modulation of swimming motility and zeamine production. Compared with the single deletion of either <i>relA</i> or <i>speA</i>, the double deletion of <i>relA</i> and <i>speA</i> could decrease the expression of RNA chaperone encoded gene <i>hfq</i> and the production of phytotoxin zeamine, which further attenuated the capability of <i>D. oryzae</i> EC1 in inhibition of rice seed germination. Collectively, the findings from this study depict alarmone ppGpp regulation on putrescine biosynthesis and transport and present the cooperation of regulation of alarmone ppGpp and putrescine in the virulence of <i>D. oryzae</i>.IMPORTANCE<i>Dickeya oryzae</i> is the causal agent of rice root rot disease. Bacterial motility and phytotoxic zeamines are characterized as two major virulent factors during <i>D. oryzea</i> infecting rice seed. Putrescine, as an interspecies and interkingdom communication signal for the infections of <i>D. oryzae</i>, has been previously demonstrated to be involved in the modulation of bacterial motility. Here we report the novel synergistic effect of putrescine signal and alarmone ppGpp on the regulation of both zeamine production and bacterial motility via modulating the expression of RNA chaperone-encoded gene <i>hfq</i>. In addition, we also showed that alarmone ppGpp hierarchically modulates putrescine biosynthesis and transport. Therefore, the findings of this study unveil the previously undetermined contribution of putrescine in the modulation of virulence determinants, and the regulatory mechanism of putrescine biosynthesis and transport in <i>D. oryzae</i>.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0068224"},"PeriodicalIF":3.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664088","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":"Diverse ssRNA viruses associated with <i>Karenia brevis</i> harmful algal blooms in southwest Florida.","authors":"Shen Jean Lim, Alexandra Rogers, Karyna Rosario, Makenzie Kerr, Matt Garrett, Julie Koester, Katherine Hubbard, Mya Breitbart","doi":"10.1128/msphere.01090-24","DOIUrl":"https://doi.org/10.1128/msphere.01090-24","url":null,"abstract":"<p><p>Harmful algal blooms (HABs) caused by the dinoflagellate <i>Karenia brevis</i> frequently occur in the eastern Gulf of Mexico, where they negatively impact the environment, human health, and economy. Very little is known about viruses associated with <i>K. brevis</i> blooms, although viral infection of other HAB-forming phytoplankton species can play an important role in bloom dynamics. We used viral metagenomics to identify viruses in 11 pooled seawater samples collected from southwest Florida, USA, in 2021 during a severe, spatiotemporally dynamic <i>K. brevis</i> bloom. Assembled viral genomes were similar to published genomes from the order <i>Picornavirales</i>, family <i>Marnaviridae</i>, and genera <i>Sogarnavirus</i>, <i>Bacillarnavirus</i>, and <i>Marnavirus</i>. Several of the cultured viruses from these groups infect bloom-forming diatoms (<i>Chaetoceros</i> sp. and <i>Rhizosolenia setigera</i>) and the raphidophyte <i>Heterosigma akashiwo</i>. We also recovered unclassified <i>Riboviria</i> genomes related to a <i>Symbiodinium</i> positive-sense ssRNA virus sequenced from coral dinoflagellate symbionts. Reverse-transcriptase PCR assays were performed to monitor the occurrence of seven representative virus genomes in these samples from 2021 and 43 seawater samples collected during a subsequent, typical bloom between November 2022 and May 2023. Over half of the samples contained multiple viruses, and at least one viral genome was detected in 44 of the 54 samples collected across seasons and years, highlighting the ubiquity of these viruses in this region. Alpha diversity was highest in the summer months and positively correlated with <i>K. brevis</i> cell counts. Multiple regression revealed month and the presence of unclassified <i>Riboviria</i> sequences most similar to dinoflagellate viruses as significant predictors of <i>K. brevis</i> cellular abundance.IMPORTANCEHarmful algal blooms caused by the dinoflagellate <i>Karenia brevis</i> negatively impact the tourism, fisheries, and public health sectors. Anticipated impacts of climate change, nutrient pollution, and ocean acidification may sustain and/or exacerbate <i>K. brevis</i> blooms in the future, underscoring the need for proactive monitoring, communication, and mitigation strategies. This study represents a pioneering effort in monitoring viruses associated with <i>K. brevis</i> blooms. The findings lay the groundwork for studying the effects of environmental drivers on <i>K. brevis</i> blooms and their associated viruses, as well as for exploring the roles of viruses in bloom dynamics and potential applications of viruses as biocontrol agents for <i>K. brevis</i> blooms. Furthermore, the comparison of viral dynamics relative to local and regional bloom dynamics in this study helps inform future monitoring and modeling needs.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0109024"},"PeriodicalIF":3.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664092","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":"mSphere of Influence: The integral art of resolving host-virus interactions.","authors":"Elliott D SoRelle","doi":"10.1128/msphere.01040-24","DOIUrl":"https://doi.org/10.1128/msphere.01040-24","url":null,"abstract":"<p><p>Elliott D. SoRelle studies viral infection and pathogenesis, specifically Epstein-Barr virus and its associated diseases, through the lens of single cell and spatial biology. In this mSphere of Influence article, he reflects on the essential value of art in biological research-and the frequent homology between the two. He incorporates themes from music and visual arts into a discussion of how three publications entitled \"The cybernetics of development\" by C. H. Waddington (<i>The Strategy of the Genes</i>, chapter 2, https://doi.org/10.4324/9781315765471), \"Epstein-Barr viral productive amplification reprograms nuclear architecture, DNA replication, and histone deposition\" by Y.-F. Chiu et al. (Cell Host Microbe 14:607-618, 2013, 10.1016/j.chom.2013.11.009), and \"Comprehensive integration of single-cell data\" by T. Stuart et al. (Cell 177:1888-1902.e21, 2019, https://doi.org/10.1016/j.cell.2019.05.031) shape his scientific perspectives in single-cell virology and provide a conceptual framework for dissecting multifaceted host-virus interactions.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0104024"},"PeriodicalIF":3.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664095","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":"Pangenomes suggest ecological-evolutionary responses to experimental soil warming.","authors":"Mallory J Choudoir, Achala Narayanan, Damayanti Rodriguez-Ramos, Rachel Simoes, Alon Efroni, Abigail Sondrini, Kristen M DeAngelis","doi":"10.1128/msphere.00059-25","DOIUrl":"https://doi.org/10.1128/msphere.00059-25","url":null,"abstract":"<p><p>Below-ground carbon transformations that contribute to healthy soils represent a natural climate change mitigation, but newly acquired traits adaptive to climate stress may alter microbial feedback mechanisms. To better define microbial evolutionary responses to long-term climate warming, we study microorganisms from an ongoing <i>in situ</i> soil warming experiment where, for over three decades, temperate forest soils are continuously heated at 5°C above ambient. We hypothesize that across generations of chronic warming, genomic signatures within diverse bacterial lineages reflect adaptations related to growth and carbon utilization. From our bacterial culture collection isolated from experimental heated and control plots, we sequenced genomes representing dominant taxa sensitive to warming, including lineages of Actinobacteria, Alphaproteobacteria, and Betaproteobacteria. We investigated genomic attributes and functional gene content to identify signatures of adaptation. Comparative pangenomics revealed accessory gene clusters related to central metabolism, competition, and carbon substrate degradation, with few functional annotations explicitly associated with long-term warming. Trends in functional gene patterns suggest genomes from heated plots were relatively enriched in central carbohydrate and nitrogen metabolism pathways, while genomes from control plots were relatively enriched in amino acid and fatty acid metabolism pathways. We observed that genomes from heated plots had less codon bias, suggesting potential adaptive traits related to growth or growth efficiency. Codon usage bias varied for organisms with similar 16S <i>rrn</i> operon copy number, suggesting that these organisms experience different selective pressures on growth efficiency. Our work suggests the emergence of lineage-specific trends as well as common ecological-evolutionary microbial responses to climate change.IMPORTANCEAnthropogenic climate change threatens soil ecosystem health in part by altering below-ground carbon cycling carried out by microbes. Microbial evolutionary responses are often overshadowed by community-level ecological responses, but adaptive responses represent potential changes in traits and functional potential that may alter ecosystem function. We predict that microbes are adapting to climate change stressors like soil warming. To test this, we analyzed the genomes of bacteria from a soil warming experiment where soil plots have been experimentally heated 5°C above ambient for over 30 years. While genomic attributes were unchanged by long-term warming, we observed trends in functional gene content related to carbon and nitrogen usage and genomic indicators of growth efficiency. These responses may represent new parameters in how soil ecosystems feedback to the climate system.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0005925"},"PeriodicalIF":3.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657460","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":"Assessment of periodontitis vaccine using three different bacterial outer membrane vesicles in canine model.","authors":"Ryoma Nakao, Takehiro Yamaguchi, Haruka Shibasaki, Jun Saeki, Aoi Takahashi, Ryunosuke Tominaga, Kimihiro Abe, Yukihiro Akeda, Tomoyo Nakagawa-Nakamura, Tomohiko Nishino, Kazuyuki Ishihara, Atsushi Jinno-Oue, Satoshi Inoue","doi":"10.1128/msphere.01033-24","DOIUrl":"https://doi.org/10.1128/msphere.01033-24","url":null,"abstract":"<p><p>Canines frequently develop periodontitis, which is similar and relevant to immunopathology and microbiology of human periodontitis. The aim of this study was to investigate whether bacterial outer membrane vesicle (OMV)-based periodontal vaccines induced humoral immune response in canines from a human vaccine development perspective. <i>Porphyromonas gingivalis</i> (Pg) and <i>Treponema denticola</i> (Td), two major periodontal pathobionts, were chosen as vaccine targets. Intranasal (IN) immunization with Pg OMVs and Td OMVs strongly elicited humoral immune responses against the two respective species in preparative mouse experiments, particularly when adjuvanted with a probiotic <i>Escherichia coli</i> derivative (EcNΔ<i>flhD</i>)-derived OMVs. However, in beagles, intranasal immunization with the same Pg/Td/EcNΔ<i>flhD</i> OMV vaccine insufficiently elicits humoral immune responses. Nevertheless, the subcutaneous booster with the same OMVs dramatically improved antibody responses in both systemic blood circulation and mucosal sites such as eyes, oral cavity, and upper and lower respiratory tracts. Metagenomic analysis of salivary microbiota revealed that the OMV vaccine might change the microbial composition, while not reducing the number of any periodontal pathobionts at least during the timeframe of the present beagle study. In <i>in vitro</i> Pg growth inhibition assay, serum samples from OMV-immunized beagles significantly inhibited growth of the gingipain-deficient strain but not the gingipain-expressing wild-type strain. Taken together, our data offer the trivalent OMV vaccine strategy by IN-prime/SC-boost regimen, which could elicit robust mucosal immune responses, while suggesting the requirement of revised periodontal vaccine regimen toward achievement of sterilizing immunity in the oral cavity.</p><p><strong>Importance: </strong>Bacterial outer-membrane vesicles (OMVs) are attractive for use as novel nanoparticle adjuvants, as well as delivery platforms. Periodontal diseases are the most prevalent oral diseases in humans and have serious health and economic burdens, greatly reducing quality of life. The aim of this study is to investigate the humoral immune responses to an OMV-based periodontal disease vaccine in beagles. The vaccine elicited strong mucosal immune responses when administered to beagles by a four-dose heterologous immunization (IN-IN-IN prime and subcutaneous [SC] boost). The OMV vaccine significantly altered the composition of the microbial community in the oral cavity. These findings suggest the utility of the intranasal (IN) prime followed by the SC boost regimen as a rational option to elicit robust humoral immune responses in canines, and most probably in humans as well. We here discuss the outcomes of beagle experiments, the mechanism behind immunological escape of Pg from host immunity, and a rational perspective toward sterilizing immunity in the oral cavity.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0103324"},"PeriodicalIF":3.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657432","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":"Rapid <i>in vitro</i> evolution of flucytosine resistance in <i>Candida auris</i>.","authors":"Trinh Phan-Canh, Duc-Minh Nguyen-Le, Phuc-Loi Luu, Narakorn Khunweeraphong, Karl Kuchler","doi":"10.1128/msphere.00977-24","DOIUrl":"https://doi.org/10.1128/msphere.00977-24","url":null,"abstract":"<p><p>The pan-antifungal-resistant pathogen <i>Candida auris</i> has been causing high-mortality infection outbreaks in hospitals and healthcare settings. The prodrug 5-fluorocytosine (5FC) is one of four chemical entities, but its clinical use as an antifungal drug has been limited owing to pronounced resistance. However, antifungal combination therapy with 5FC appears as a promising strategy for treating <i>C. auris</i> infections. Here, we show that a <i>C. auris</i> clinical isolate can rapidly acquire genetic mutations to mount 5FC resistance after only one to two passages under drug selection. We exploit a new bioinformatics workflow to identify genetic polymorphisms from RNA-seq data. Strikingly, we identify several mutations in the <i>FUR1</i> gene encoding the 5-fluorouracil convertase that normally generates the active drug. A single nonsense mutation truncates the enzyme at residue Q30*, leading to 5FC resistance due to inactive Fur1. Whole-genome sequencing analysis revealed that an indel mutation in <i>FCY2</i> also contributes to 5FC resistance. Furthermore, at least one out of seven adapted strains acquired enhanced 5FC tolerance without mutations in the 5FC conversion pathway. Thus, we demonstrate that <i>FUR1</i> mutations are critical drivers of 5FC resistance in <i>C. auris</i>.IMPORTANCE<i>Candida auris</i> is a high-priority human fungal pathogen, causing infection outbreaks of high mortality in healthcare settings. Antifungal combination therapy with 5-fluorocytosine (5FC) is one of the emerging approaches in treatment. However, acquired 5FC resistance traits have been a matter of concern. 5FC is taken up by fungal cells via a cytosine permease and further metabolized by a cytosine deaminase to 5-fluorouracil (5FU). 5FU is then converted by the Fur1 uracil phosphoribosyltransferase into a toxic antimetabolite that disrupts fungal RNA and DNA syntheses. Mutations in these proteins are commonly associated with 5FC resistance in fungal species. Here, we show that <i>C. auris</i> can rapidly develop resistance under 5FC selective stress owing to mutational inactivation of Fur1 function. Moreover, other mechanisms that bypass mutations in the 5FC conversion pathway may also contribute to 5FC resistance traits. Finally, we have developed a tailored bioinformatics workflow that facilitates the identification of polymorphisms associated with 5FC resistance in clinical isolates.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0097724"},"PeriodicalIF":3.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657509","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":"Toxoplasmosis accelerates the progression of hereditary spastic paraplegia.","authors":"James R Alvin, Carlos J Ramírez-Flores, Caitlin A Mendina, Anjon Audhya, Laura J Knoll, Molly M Lettman","doi":"10.1128/msphere.00826-24","DOIUrl":"https://doi.org/10.1128/msphere.00826-24","url":null,"abstract":"<p><p>The parasitic protozoa <i>Toxoplasma gondii</i> chronically infects the central nervous system of an estimated one-third of the human population. Infection is generally subclinical, but immunocompromised individuals can experience a variety of neurological symptoms. Meta-analyses of <i>T. gondii</i> seropositivity have suggested a correlation between <i>T. gondii</i> infection and neurologic disease. Although mechanistic studies on the relationship between <i>T. gondii</i> infection and neurologic disease have been attempted in mice, they are particularly susceptible to <i>T. gondii</i>, making them an effective model for investigating mechanisms of infection, but not ideal for examining the relationship between long-term chronic <i>T. gondii</i> infection and neurologic disease. Rats more closely mimic human <i>T. gondii</i> cyst levels after acute infection, but a lack of rat models for neurologic disease has limited studies on the interplay between <i>T. gondii</i> infection and neurologic disease progression. We have employed a previously characterized rat model of a complex form of hereditary spastic paraplegia (HSP), a class of neurodegenerative disorders that cause axonal degeneration and lower limb spasticity, in order to assess the effect of chronic <i>T. gondii</i> infection on neurodegenerative disease. We find that infected rats with hereditary spastic paraplegia exhibit significantly exacerbated behavioral and neuromorphological HSP symptoms compared with uninfected HSP mutant rats, with little correlative effect in infected versus uninfected control animals. We further find that all infected rats, regardless of genotype, exhibit a robust immune response to <i>T. gondii</i> infection, presenting with parasite levels below the limit of detection of multiple assays of parasitemia and exhibiting no detectable increase in neuroinflammation 7 weeks post-infection. These results suggest that chronic undetected <i>T. gondii</i> infection may exacerbate neurodegenerative disease even in immunocompetent individuals and may contribute to neurodegenerative disease heterogeneity.IMPORTANCEThe long-term consequences of previous acute infections are poorly understood but are becoming increasingly appreciated, particularly in the era of long COVID. Altered progression of other diseases later in life may be among the long-term consequences of previous infections. Here, we investigate the relationship between previous infections with the parasite <i>Toxoplasma gondii</i>, which infects ~30% of the global population, and neurodegenerative disease using a rat model of hereditary spastic paraplegia (HSP). We find that previous infections with <i>T. gondii</i> accelerate motor dysfunction in HSP rats, despite robust clearance of the parasite by infected rats. Our results suggest that previously cleared infections may alter the progression of other diseases later in life and contribute to neurodegenerative disease heterogeneity.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0082624"},"PeriodicalIF":3.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657510","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":"ASM and the UN SDG Publishers Compact: year one.","authors":"Lorraine F Clark, Amanda Donaldson, Michael E Lerman","doi":"10.1128/msphere.00116-25","DOIUrl":"https://doi.org/10.1128/msphere.00116-25","url":null,"abstract":"<p><p>The United Nations (UN) Sustainable Development Goals (SDG) represent an important set of global priorities, addressing the most urgent environmental, economic, and social challenges facing humankind. The American Society for Microbiology (ASM) signed the UN SDG Publishers Compact in March 2024, to lend its voice to this vital initiative, as indeed not only do the SDGs align with ASM's mission but microbes themselves can play significant roles in, for example, sustainable agriculture, clean energy, and human health. In its first year as a signatory, ASM has pursued, published, and highlighted sustainability-focused work in its journals, has raised awareness through internal efforts and joint efforts with other scientific organizations, and has prioritized the SDGs in its conferences and other programs. We commemorate our achievements in this first year and look forward to future initiatives, innovations, and collaborations toward a sustainable future.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0011625"},"PeriodicalIF":3.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649865","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":"Integrated multi-omics to elucidate the interplay between rumen microorganisms and host metabolism in Hu sheep supplemented with herbal preparations.","authors":"Chunhui Wang, Qiao Li, Xingcai Qi, Huihui Wang, Yi Wu, Keyan Ma, Juanjuan Song, Zilong Liu, Youji Ma","doi":"10.1128/msphere.00024-25","DOIUrl":"https://doi.org/10.1128/msphere.00024-25","url":null,"abstract":"&lt;p&gt;&lt;p&gt;The aim of this experiment was to study the effects of herbal preparations on serum metabolites, rumen microorganisms, and their metabolites, and the relationship between them. Hu sheep ram lambs with an average initial weight of (19.57 ± 1.56 kg) at 3 months of age were selected and randomly divided into three groups of six lambs each. The groups were as follows: the control group (Con), which was fed the basic diet; Test I, which was fed a diet with 0.5% herbal preparations added to the concentrate; and Test II, which was fed a diet with 1% herbal preparations added to the concentrate. Also, the main component of herbal medicine is polysaccharide. The pre-experimental period was 10 days and the experimental period was 90 days. The results of the study showed that the addition of herbal preparations resulted in differences in species, abundance, and metabolic functions of rumen microorganisms. The abundance of rumen-dominant bacteria, such as Firmicutes and Proteobacteria, increased after the addition of herbal preparation, which was more conducive to rumen development. In addition, after the addition of 0.5% herbal preparation, there was an increase in the abundance of fermenting carbohydrate (CHO) and fiber-degrading bacteria (e.g., &lt;i&gt;Ruminococcus&lt;/i&gt; and &lt;i&gt;Prevotella&lt;/i&gt;). Herbal preparations significantly altered rumen microorganisms and serum metabolite compositions. Metabolites such as bile acids, L-glutamine, cytosine, and choline, which contribute to the antiviral and anti-inflammatory effects, nutrient metabolism, and immune responses, and increased rumen microbial activity, were increased in the rumen of the experimental group with the addition of the herbal preparations. The increase in serum metabolites, such as L-tryptophan, and the pathways of tryptophan metabolism and glutathione metabolism in animals were also significantly higher than those in Con. &lt;i&gt;Prevotella&lt;/i&gt; and &lt;i&gt;Ruminococcus&lt;/i&gt; were significantly positively correlated with histamine and L-arginine. The &lt;i&gt;uncultured_rumen_bacterium&lt;/i&gt; was significantly negatively correlated with serum metabolites testosterone and guanine, but &lt;i&gt;Prevotella&lt;/i&gt; and &lt;i&gt;Ruminococcus&lt;/i&gt; were significantly positively correlated with both metabolite testosterone and guanine.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;In this study, we investigated the changes in rumen microbes after supplementation with herbal preparations. We used 16S sequencing and metabolomics approaches to explore changes in rumen contents and serum metabolites and their interrelationships. Our findings revealed marked changes in rumen microbial profiles, including changes in species composition, abundance levels, and metabolic activities induced by herbal supplementation. The increased abundance of beneficial bacteria (e.g., fixative and proteobacteria) in the rumen was more favorable for their survival and colonization of the rumen. In addition, a surge in the abundance of fermenting carbohydrate and fiber-degradin","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0002425"},"PeriodicalIF":3.7,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625083","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":"Less reactogenic whole-cell pertussis vaccine confers protection from <i>Bordetella pertussis</i> infection.","authors":"Karolína Škopová, Jana Holubová, Barbora Bočková, Eva Slivenecká, João Melo Santos de Barros, Ondřej Staněk, Peter Šebo","doi":"10.1128/msphere.00639-24","DOIUrl":"https://doi.org/10.1128/msphere.00639-24","url":null,"abstract":"<p><p>Pertussis resurged over the last decade in most countries that replaced the traditional whole-cell pertussis vaccines (wP) by the less reactogenic acellular pertussis vaccines (aP). The aP vaccines induce a Th2-polarized immune response and by a yet unknown mechanism hamper the clearance of <i>Bordetella pertussis</i> from infected nasopharyngeal mucosa. The aP-induced pertussis toxin-neutralizing antibodies effectively prevent the life-threatening pertussis pneumonia in infants, but aP-elicited immunity fails to prevent infection of nasopharyngeal mucosa and transmission of <i>B. pertussis</i>. In contrast, the more reactogenic traditional wP vaccines, alike natural infection, elicit a broad antibody response and trigger a Th1/Th17-polarized T cell immunity. We tackled here the reactogenicity of the conventional wP vaccines by genetic modification of the Fim2 and Fim3-producing <i>B. pertussis</i> strains used for wP vaccine manufacturing. Mutations were introduced into the genomes of vaccine strains (i) to reduce the TLR4 signaling potency of the lipid A of <i>B. pertussis</i> lipooligosaccharide (Δ<i>lgm</i>B), (ii) eliminate the enzymatic (immunosuppressive) activity of the pertussis toxin (PtxS1-R9K/E129G), and (iii) ablate the production of the dermonecrotic toxin (Δ<i>dnt</i>). Experimental alum-adjuvanted wP vaccines prepared from such triply modified bacteria exhibited a reduced pyrogenicity in rabbits and a reduced systemic toxicity in mice, while conferring a comparable protection from <i>B. pertussis</i> infection as the unmodified wP vaccine.IMPORTANCEThe occasionally severe adverse reactions associated with some lots of the whole-cell pertussis vaccine (wP) led the industrialized nations to switch to the use of less reactogenic acellular pertussis vaccines that confer shorter-lasting protection. This yielded whooping cough resurgence and large whooping cough outbreaks are currently sweeping throughout European countries, calling for the replacement of the pertussis vaccine component of pediatric hexavaccines by an improved wP vaccine. We show that genetic detoxification of the <i>Bordetella pertussis</i> bacteria used for wP preparation yields a reduced reactogenicity wP vaccine that exhibits a reduced systemic toxicity in mice and reduced pyrogenicity in rabbits, while retaining high immunogenicity and protective potency in the mouse model of pneumonic infection by <i>B. pertussis</i>. This result has now been confirmed in a nonhuman primate model of <i>B. pertussis</i> infection of olive baboons, paving the way for the development of the next generation of pertussis vaccines.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0063924"},"PeriodicalIF":3.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605931","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}