mSystems最新文献

{"title":"Evolution and maintenance of a large multidrug-resistant plasmid in a <i>Salmonella enterica</i> Typhimurium host under differing antibiotic selection pressures.","authors":"Ming Cheng, Jing-Jing Dai, Jin-Fei Zhang, Yu-Ting Su, Si-Qi Guo, Ruan-Yang Sun, Dong Wang, Jian Sun, Xiao-Ping Liao, Sheng Chen, Liang-Xing Fang","doi":"10.1128/msystems.01197-24","DOIUrl":"10.1128/msystems.01197-24","url":null,"abstract":"&lt;p&gt;&lt;p&gt;The dissemination of antibiotic resistance genes (ARGs) through plasmids is a major mechanism for the development of bacterial antimicrobial resistance. The adaptation and evolution mechanisms of multidrug-resistant (MDR) plasmids with their hosts are not fully understood. Herein, we conducted experimental evolution of a 244 kb MDR plasmid (pJXP9) under various conditions including no antibiotics and mono- or combinational drug treatments of colistin (CS), cefotaxime (CTX), and ciprofloxacin (CIP). Our results showed that long-term with or without positive selections for pJXP9, spanning approximately 600 generations, led to modifications of the plasmid-encoded MDR and conjugative transfer regions. These modifications could mitigate the fitness cost of plasmid carriage and enhance plasmid maintenance. The extent of plasmid modifications and the evolution of plasmid-encoded antibiotic resistance depended on treatment type, particularly the drug class and duration of exposure. Interestingly, prolonged exposure to mono- and combinational drugs of CS and CIP resulted in a substantial loss of the plasmid-encoded MDR region and antibiotic resistance, comparable to the selection condition without antibiotic. By contrast, combinational treatment with CTX contributed to the maintenance of the MDR region over a long period of time. Furthermore, drug selection was able to maintain and even amplify the corresponding plasmid-encoded ARGs, with co-selection of ARGs in the adjacent regions. In addition, parallel mutations in chromosomal &lt;i&gt;arcA&lt;/i&gt; were also found to be associated with pJXP9 plasmid carriage among endpoint-evolved clones from diverse treatments. Meanwhile, &lt;i&gt;arcA&lt;/i&gt; deletion improved the persistence of pJXP9 plasmid without drugs. Overall, our findings indicated that plasmid-borne MDR region deletion and chromosomal &lt;i&gt;arcA&lt;/i&gt; inactivation mutation jointly contributed to co-adaptation and co-evolution between MDR IncHI2 plasmid and &lt;i&gt;Salmonella&lt;/i&gt; Typhimurium under different drug selection pressure.IMPORTANCEThe plasmid-mediated dissemination of antibiotic resistance genes has become a significant concern for human health, even though the carriage of multidrug-resistant (MDR) plasmids is frequently associated with fitness costs for the bacterial host. However, the mechanisms by which MDR plasmids and bacterial pairs evolve plasmid-mediated antibiotic resistance in the presence of antibiotic selections are not fully understood. Herein, we conducted an experimental evolution of a large multidrug-resistant plasmid in a &lt;i&gt;Salmonella enterica&lt;/i&gt; Typhimurium host under single and combinatorial drug selection pressures. Our results show the adaptive evolution of plasmid-encoded antibiotic resistance through alterations of the MDR region in the plasmid, in particular substantial loss of the MDR region, in response to different positive selections, especially mono- and combinational drugs of colistin and ciprofloxacin. In addition, strong pa","PeriodicalId":18819,"journal":{"name":"mSystems","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470279","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":"Annotation-free prediction of microbial dioxygen utilization.","authors":"Avi I Flamholz, Joshua E Goldford, Philippa A Richter, Elin M Larsson, Adrian Jinich, Woodward W Fischer, Dianne K Newman","doi":"10.1128/msystems.00763-24","DOIUrl":"10.1128/msystems.00763-24","url":null,"abstract":"<p><p>Aerobes require dioxygen (O₂) to grow; anaerobes do not. However, nearly all microbes-aerobes, anaerobes, and facultative organisms alike-express enzymes whose substrates include O₂, if only for detoxification. This presents a challenge when trying to assess which organisms are aerobic from genomic data alone. This challenge can be overcome by noting that O₂ utilization has wide-ranging effects on microbes: aerobes typically have larger genomes encoding distinctive O₂-utilizing enzymes, for example. These effects permit high-quality prediction of O₂ utilization from annotated genome sequences, with several models displaying ≈80% accuracy on a ternary classification task for which blind guessing is only 33% accurate. Since genome annotation is compute-intensive and relies on many assumptions, we asked if annotation-free methods also perform well. We discovered that simple and efficient models based entirely on genomic sequence content-e.g., triplets of amino acids-perform as well as intensive annotation-based classifiers, enabling rapid processing of genomes. We further show that amino acid trimers are useful because they encode information about protein composition and phylogeny. To showcase the utility of rapid prediction, we estimated the prevalence of aerobes and anaerobes in diverse natural environments cataloged in the Earth Microbiome Project. Focusing on a well-studied O₂ gradient in the Black Sea, we found quantitative correspondence between local chemistry (O₂:sulfide concentration ratio) and the composition of microbial communities. We, therefore, suggest that statistical methods like ours might be used to estimate, or \"sense,\" pivotal features of the chemical environment using DNA sequencing data.IMPORTANCEWe now have access to sequence data from a wide variety of natural environments. These data document a bewildering diversity of microbes, many known only from their genomes. Physiology-an organism's capacity to engage metabolically with its environment-may provide a more useful lens than taxonomy for understanding microbial communities. As an example of this broader principle, we developed algorithms that accurately predict microbial dioxygen utilization directly from genome sequences without annotating genes, e.g., by considering only the amino acids in protein sequences. Annotation-free algorithms enable rapid characterization of natural samples, highlighting quantitative correspondence between sequences and local O₂ levels in a data set from the Black Sea. This example suggests that DNA sequencing might be repurposed as a multi-pronged chemical sensor, estimating concentrations of O₂ and other key facets of complex natural settings.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11494890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126170","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":"Unfolding and de-confounding: biologically meaningful causal inference from longitudinal multi-omic networks using METALICA.","authors":"Daniel Ruiz-Perez, Isabella Gimon, Musfiqur Sazal, Kalai Mathee, Giri Narasimhan","doi":"10.1128/msystems.01303-23","DOIUrl":"10.1128/msystems.01303-23","url":null,"abstract":"<p><p>A key challenge in the analysis of microbiome data is the integration of multi-omic datasets and the discovery of interactions between microbial taxa, their expressed genes, and the metabolites they consume and/or produce. In an effort to improve the state of the art in inferring biologically meaningful multi-omic interactions, we sought to address some of the most fundamental issues in causal inference from longitudinal multi-omics microbiome data sets. We developed METALICA, a suite of tools and techniques that can infer interactions between microbiome entities. METALICA introduces novel unrolling and de-confounding techniques used to uncover multi-omic entities that are believed to act as confounders for some of the relationships that may be inferred using standard causal inferencing tools. The results lend support to predictions about biological models and processes by which microbial taxa interact with each other in a microbiome. The unrolling process helps identify putative intermediaries (genes and/or metabolites) to explain the interactions between microbes; the de-confounding process identifies putative common causes that may lead to spurious relationships to be inferred. METALICA was applied to the networks inferred by existing causal discovery, and network inference algorithms were applied to a multi-omics data set resulting from a longitudinal study of IBD microbiomes. The most significant unrollings and de-confoundings were manually validated using the existing literature and databases.</p><p><strong>Importance: </strong>We have developed a suite of tools and techniques capable of inferring interactions between microbiome entities. METALICA introduces novel techniques called unrolling and de-confounding that are employed to uncover multi-omic entities considered to be confounders for some of the relationships that may be inferred using standard causal inferencing tools. To evaluate our method, we conducted tests on the inflammatory bowel disease (IBD) dataset from the iHMP longitudinal study, which we pre-processed in accordance with our previous work. From this dataset, we generated various subsets, encompassing different combinations of metagenomics, metabolomics, and metatranscriptomics datasets. Using these multi-omics datasets, we demonstrate how the unrolling process aids in the identification of putative intermediaries (genes and/or metabolites) to explain the interactions between microbes. Additionally, the de-confounding process identifies potential common causes that may give rise to spurious relationships to be inferred. The most significant unrollings and de-confoundings were manually validated using the existing literature and databases.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11494969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140577","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":"Enormous diversity of RNA viruses in economic crustaceans.","authors":"Xuan Dong, Fanzeng Meng, Chengyan Zhou, Juan Li, Tao Hu, Yiting Wang, Guohao Wang, Jingfei Luo, Xuan Li, Shufang Liu, Jie Huang, Weifeng Shi","doi":"10.1128/msystems.01016-24","DOIUrl":"10.1128/msystems.01016-24","url":null,"abstract":"<p><p>Crustaceans are important food sources worldwide and possess significant ecological status in the marine ecosystem. However, our understanding of the diversity and evolution of RNA viruses in crustaceans, especially in economic crustaceans, is still limited. Here, 106 batches of economic crustaceans including 13 species were collected from 24 locations in China during 2016-2021. We identified 90 RNA viruses, 69 of which were divergent from the known viruses. Viral transcripts were assigned to 18 different viral families/clades and three unclassified groups. Among the identified viruses, five were double-stranded RNA viruses, 74 were positive-sense single-stranded RNA (+ssRNA) viruses, nine were negative-sense single-stranded RNA (-ssRNA) viruses, and two belonged to an unclassified RNA virus group. Phylogenetic analyses showed that crustacean viruses were often clustered with viruses identified from invertebrates. Remarkably, most crustacean viruses were closely related to those from different host species along the same food chain or ecological aquatic niche. In addition, the genome structures of the newly discovered picornaviruses exhibited remarkable diversity. Our study significantly expands the diversity of viruses in important economic crustaceans and provides essential data for the risk assessment of the pathogens spreading in the global aquaculture industry.</p><p><strong>Importance: </strong>The study delves into the largely uncharted territory of RNA viruses in crustaceans, which are not only vital for global food supply but also play a pivotal role in marine ecosystems. Focusing on economic crustaceans, the research uncovers 90 RNA viruses, with 69 being potentially new to science, highlighting the vast unknown viral diversity within these marine organisms. The findings reveal that these viruses are often related to those found in other invertebrates and tend to share close relationships with viruses from species within the same food web or habitat. This suggests that viruses may move between different marine species more frequently than previously thought. The discovery of such a wide variety of viruses, particularly the diverse genome structures of newly identified picornaviruses, is a significant leap forward in understanding the crustacean virology. This knowledge is crucial for managing disease risks in aquaculture and maintaining the balance of marine ecosystems.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11494968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350272","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":"Microevolution of <i>Bartonella grahamii</i> driven by geographic and host factors.","authors":"Ailing Xu, Liang Lu, Wen Zhang, Xiuping Song, Guichang Li, Yu Miao, Ruixiao Li, Min Chen, Qiyong Liu, Dongmei Li","doi":"10.1128/msystems.01089-24","DOIUrl":"10.1128/msystems.01089-24","url":null,"abstract":"<p><p><i>Bartonella grahamii</i> is one of the most prevalent <i>Bartonella</i> species in wild rodents and has been associated with human cases of neuroretinitis. The structure and distribution of genomic diversity in natural <i>B. grahamii</i> is largely unexplored. Here, we have applied a comprehensive population genomic and phylogenomic analysis to 172 strains of <i>B. grahamii</i> to unravel the genetic differences and influencing factors that shape its populations. The findings reveal a remarkable genomic diversity within the species, primarily in the form of single- nucleotide polymorphisms. The open pangenome of <i>B. grahamii</i> indicates a dynamic genomic evolution influenced by its ecological niche. Whole-genome data allowed us to decompose <i>B. grahamii</i> diversity into six phylogroups, each characterized by a unique \"mosaic pattern\" of hosts and biogeographic regions. This suggests a complex interplay between host specificity and biogeography. In addition, our study suggests a possible origin of European strains from Asian lineages, and host factors have a more significant impact on the genetic differentiation of <i>B. grahamii</i> than geographical factors. These insights contribute to understanding the evolutionary history of this pathogen and provide a foundation for future epidemiological research and public health strategies.</p><p><strong>Importance: </strong><i>Bartonella grahamii</i> has been reported worldwide and shown to infect humans. Up to now, an effective transmission route of <i>B. grahamii</i> to humans has not been confirmed. The genetic evolution of <i>B. grahamii</i> and the relationship between <i>B. grahamii</i> and its host need to be further studied. The factors driving the genetic diversity of <i>B. grahamii</i> are still controversial. The results showed that the European isolates shared a common ancestor with the Chinese isolates. Host factors were shown to play an important role in driving the genetic diversity of <i>B. grahamii</i>. When host factors were fixed, geographic barriers drove <i>B. grahamii</i> microevolution. Our study emphasizes the importance of characterizing isolate genomes derived from hosts and geographical locations and provides a new reference for the origin of <i>B. grahamii</i>.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11494883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350274","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":"Gut microbiome and serum metabolome alterations associated with lactose intolerance (LI): a case‒control study and paired-sample study based on the American Gut Project (AGP).","authors":"Hong Xue, Yitian Wang, Chunfeng Mei, Lili Han, Mengxiong Lu, Xuan Li, Ting Chen, Fengyun Wang, Xudong Tang","doi":"10.1128/msystems.00839-24","DOIUrl":"10.1128/msystems.00839-24","url":null,"abstract":"<p><p>Lactose intolerance (LI) is a prevalent condition characterized by gastrointestinal symptoms that arise following lactose consumption. Recent evidence suggests that the gut microbiome may influence lactose levels in the gut. However, there is limited understanding regarding the alterations in microbiota and metabolism between individuals with LI and non-LI. This study conducted a paired-sample investigation utilizing data from the American Gut Project (AGP) and performed metagenomic and untargeted metabolomic analyses in a Chinese cohort to explore the interaction between the gut microbiome and serum metabolites. In addition, fecal microbiota transplantation (FMT) experiments were conducted to further examine the impact of the LI-associated gut microbiome on inflammatory outcomes. We identified 14 microbial genera that significantly differed between LI and controls from AGP data. Using a machine learning approach, group separation was predicted based on seven species and nine metabolites in the Chinese cohort. Notably, increased levels of <i>Escherichia coli</i> in the LI group were negatively correlated with several metabolites, including PC (22:6/0:0), indole, and Lyso PC, while reduced levels of <i>Faecalibacterium prausnitzii</i> and <i>Eubacterium rectale</i> were positively correlated with indole and furazolidone. FMT-LI rats displayed visceral hypersensitivity and an altered gut microbiota composition compared to FMT-HC rats. Metagenomic and metabolomic analyses revealed an enrichment of MAPK signaling in LI, which was confirmed by FMT-LI rats showing higher expression of ERK and RAS, along with increased concentrations of proinflammatory cytokines. This study provides valuable insights into the disrupted microbial and metabolic traits associated with LI, emphasizing potential microbiome-based approaches for its prevention and treatment.</p><p><strong>Importance: </strong>Lactose intolerance (LI) is a prevalent condition characterized by gastrointestinal symptoms after lactose consumption due to a deficiency of lactase. There is limited understanding regarding the microbiota and metabolic alterations between individuals with LI and non-LI. This study represents the first exploration to investigate metagenomic and metabolomic signatures among subjects with lactose intolerance as far as our knowledge. We identified 14 microbial genera in the Western cohort and 7 microbial species, along with 9 circulating metabolites in the Chinese cohort, which significantly differed in LI patients. Metagenomic and metabolomic analyses revealed an enrichment of MAPK signaling in LI patients. This finding was confirmed by FMT-LI rats, exhibiting increased expression of ERK and RAS, along with higher concentrations of pro-inflammatory cytokines. Our study provides insights into the disrupted functional and metabolic traits of the gut microbiome in LI, highlighting potential microbiome-based approaches for preventing and treating LI.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11494873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350273","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":"Gut microbiota-derived gamma-aminobutyric acid improves host appetite by inhibiting satiety hormone secretion.","authors":"Shouren Li, Mengqi Liu, Yao Han, Cong Liu, Shixi Cao, Yalei Cui, Xiaoyan Zhu, Zhichang Wang, Boshuai Liu, Yinghua Shi","doi":"10.1128/msystems.01015-24","DOIUrl":"10.1128/msystems.01015-24","url":null,"abstract":"<p><p>Globally, appetite disorders have become an increasingly prominent public health issue. While short-term appetite loss may seem relatively harmless, prolonged instances can lead to serious physical and mental damage. In recent years, numerous studies have highlighted the significant role of the \"microbiota-gut-brain\" axis in the regulation of feeding behavior in organisms, suggesting that targeting the gut microbiota may be a novel therapeutic strategy for appetite disorders. However, the molecular mechanisms through which the gut microbiota mediates the increase in host appetite and the causal relationship between the two remain unclear. Based on this, we conducted 16S rRNA sequencing to analyze the gut microbiota of rabbits with high and low feed intake, followed by fecal microbiota transplantation (FMT) and metabolite gavage experiments to elucidate the underlying mechanisms. Our research indicates that the high feed intake group exhibited significant enrichment of the <i>g__Bacteroides</i> and gamma-aminobutyric acid (GABA), and intragastric administration of GABA effectively promoted the host's feeding behavior. The underlying mechanism involves GABA derived from the gut microbiota inhibiting the secretion of satiety hormones to enhance the host's feeding behavior. Furthermore, the results of FMT suggest that differences in gut microbiota composition may be a contributing factor to varying levels of feed intake in the host. In conclusion, these findings emphasize the role of the gut microbiota-derived GABA, in increasing host feed intake, offering a new target for the treatment of appetite disorders from the perspective of gut microbiota.IMPORTANCEThe incidence of anorexia is rapidly increasing and has become a global burden. Gut microbiota can participate in the regulation of host feeding behavior, yet the molecular mechanisms through which the gut microbiota mediates the increase in host appetite and the causal relationship between them remain unclear. In this study, we utilized 16S rRNA sequencing to investigate the composition of the gut microbiota in rabbits with varying levels of feed intake and employed fecal microbiota transplantation and gastric infusion experiments with gamma-aminobutyric acid (GABA) to elucidate the potential mechanisms involved. GABA derived from the gut microbiota can effectively enhance the host's feeding behavior by inhibiting the secretion of satiety hormones. This discovery underscores the pivotal role of the gut microbiota in modulating host appetite, offering novel research avenues and therapeutic targets for appetite disorders.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11495008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308107","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":"Single-colony MALDI mass spectrometry imaging reveals spatial differences in metabolite abundance between natural and cultured <i>Trichodesmium</i> morphotypes.","authors":"Karl J Romanowicz, Futing Zhang, Siyuan Wang, Dušan Veličković, Rosalie K Chu, Yeala Shaked, Rene M Boiteau","doi":"10.1128/msystems.01152-24","DOIUrl":"10.1128/msystems.01152-24","url":null,"abstract":"<p><p><i>Trichodesmium</i>, a globally significant N₂-fixing marine cyanobacterium, forms extensive surface blooms in nutrient-poor ocean regions. These blooms consist of a dynamic assemblage of <i>Trichodesmium</i> species that form distinct colony morphotypes and are inhabited by diverse microorganisms. <i>Trichodesmium</i> colony morphotypes vary in ecological niche, nutrient uptake, and organic molecule release, differentially impacting ocean carbon and nitrogen biogeochemical cycles. Here, we assessed the poorly studied spatial abundance of metabolites within and between three morphologically distinct <i>Trichodesmium</i> colonies collected from the Red Sea. We also compared these results with two morphotypes of the cultivable <i>Trichodesmium</i> strain IMS101. Using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) coupled with liquid extraction surface analysis (LESA) tandem mass spectrometry (MS²), we identified and localized a wide range of small metabolites associated with single-colony <i>Trichodesmium</i> morphotypes. Our untargeted MALDI-MSI approach revealed 80 unique features (metabolites) shared between <i>Trichodesmium</i> morphotypes. Discrimination analysis showed spatial variations in 57 shared metabolites, accounting for 62% of the observed variation between morphotypes. The greatest variations in metabolite abundance were observed between the cultured morphotypes compared to the natural colony morphotypes, suggesting substantial differences in metabolite production between the cultivable strain IMS101 and the naturally occurring colony morphotypes that the cultivable strain is meant to represent. This study highlights the variations in metabolite abundance between natural and cultured <i>Trichodesmium</i> morphotypes and provides valuable insights into metabolites common to morphologically distinct <i>Trichodesmium</i> colonies, offering a foundation for future targeted metabolomic investigations.IMPORTANCEThis work demonstrates that the application of spatial mass spectrometry imaging at single-colony resolution can successfully resolve metabolite differences between natural and cultured <i>Trichodesmium</i> morphotypes, shedding light on their distinct biochemical profiles. Understanding the morphological differences between <i>Trichodesmium</i> colonies is crucial because they impact nutrient uptake, organic molecule production, and carbon and nitrogen export, and subsequently influence ocean biogeochemical cycles. As such, our study serves as an important initial assessment of metabolite differences between distinct <i>Trichodesmium</i> colony types, identifying features that can serve as ideal candidates for future targeted metabolomic studies.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11501100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308155","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":"Activation of NF-κB/MAPK signaling and induction of apoptosis by salicylate synthase NbtS in <i>Nocardia farcinica</i> promotes neuroinflammation development.","authors":"Jirao Shen, Xing Zhao Ji, Lichao Han, Jiang Yao, Yihe Liang, Min Yuan, Shuai Xu, Zhenjun Li","doi":"10.1128/msystems.00893-24","DOIUrl":"10.1128/msystems.00893-24","url":null,"abstract":"<p><p><i>Nocardia farcinica</i> can cause a rare, yet potentially fatal, central nervous system infection. NbtS protein may be a key virulence factor in <i>N. farcinica</i> infection of the brain. In this study, we investigated the function of the virulence-associated factor NbtS in microglial cells <i>in vitro</i> and in infected mice <i>in vivo</i>. We explored the interactions between NbtS and microglial cells (BV2 and human microglial clone 3), revealing that NbtS activates the toll-like receptor 4-dependent MyD88-IRAK4-IRAK1 and MAPK/nuclear factor kappa B (NF-κB) pathways, significantly enhancing pro-inflammatory responses as indicated by increased levels of tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β), as measured by ELISA and quantitative PCR. Apoptosis was elevated in these cells, as shown by increased expression of Bax and caspase-3 and decreased Bcl-2 levels. The terminal deoxynucleotidyl transferase dUTP nick end labeling assay also confirmed the occurrence of apoptosis. In vivo, mice infected with an <i>RS03155</i>-deficient strain of <i>N. farcinica</i> exhibited higher survival rates and reduced brain inflammation, suggesting a pivotal role for the NbtS protein in the pathogenesis of <i>Nocardia</i>. Conservation of the <i>RS03155</i> gene across <i>Nocardia</i> spp. was verified by PCR, and the immunogenic potential of NbtS was confirmed by Western blot analysis using sera from infected mice. These findings suggest that targeting NbtS may offer a novel therapeutic strategy against <i>Nocardia</i> infection.</p><p><strong>Importance: </strong>The study presented in this article delves into the molecular underpinnings of <i>Nocardia farcinica</i>-induced neuroinflammation. By focusing on the salicylate synthase gene, <i>RS03155</i>, and its encoded protein, NbtS, we uncover a pivotal virulence factor that triggers a cascade of immunological responses leading to apoptosis in microglial cells. This research not only enhances our comprehension of the pathogenesis of <i>Nocardia</i> infections but also provides a potential therapeutic target. Given the rising importance of understanding host-microbe interactions within the context of the central nervous system, especially in immunocompromised individuals, the findings are of significant relevance to the field of microbiology and could inform future diagnostic and treatment modalities for <i>Nocardia</i>-associated neurological disorders. Our work emphasizes the need for continued research into the intricate mechanisms of microbial pathogenesis and the development of novel strategies to combat life-threatening infections.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11494946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140576","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":"Aerobic adaptation and metabolic dynamics of <i>Propionibacterium freudenreichii</i> DSM 20271: insights from comparative transcriptomics and surfaceome analysis.","authors":"Iida Loivamaa, Annika Sillanpää, Paulina Deptula, Bhawani Chamlagain, Minnamari Edelmann, Petri Auvinen, Tuula A Nyman, Kirsi Savijoki, Vieno Piironen, Pekka Varmanen","doi":"10.1128/msystems.00615-24","DOIUrl":"10.1128/msystems.00615-24","url":null,"abstract":"<p><p><i>Propionibacterium freudenreichii</i> (<i>PFR</i>) DSM 20271^T is a bacterium known for its ability to thrive in diverse environments and to produce vitamin B12. Despite its anaerobic preference, recent studies have elucidated its ability to prosper in the presence of oxygen, prompting a deeper exploration of its physiology under aerobic conditions. Here, we investigated the response of DSM 20271^T to aerobic growth by employing comparative transcriptomic and surfaceome analyses alongside metabolite profiling. Cultivation under controlled partial pressure of oxygen (pO₂) conditions revealed significant increases in biomass formation and altered metabolite production, notably of vitamin B12, pseudovitamin-B12, propionate, and acetate, under aerobic conditions. Transcriptomic analysis identified differential expression of genes involved in lactate metabolism, tricarboxylic acid cycle, and electron transport chain, suggesting metabolic adjustments to aerobic environments. Moreover, surfaceome analysis unveiled growth environment-dependent changes in surface protein abundance, with implications for adaptation to atmospheric conditions. Supplementation experiments with key compounds highlighted the potential for enhancing aerobic growth, emphasizing the importance of iron and α-ketoglutarate availability. Furthermore, in liquid culture, FeSO₄ supplementation led to increased heme production and reduced vitamin B12 production, highlighting the impact of oxygen and iron availability on the metabolic pathways. These findings deepen our understanding of <i>PFR</i>'s physiological responses to oxygen availability and offer insights for optimizing its growth in industrial applications.</p><p><strong>Importance: </strong>The study of the response of <i>Propionibacterium freudenreichii</i> to aerobic growth is crucial for understanding how this bacterium adapts to different environments and produces essential compounds like vitamin B12. By investigating its physiological changes under aerobic conditions, we can gain insights into its metabolic adjustments and potential for enhanced growth. These findings not only deepen our understanding of <i>P. freudenreichii'</i>s responses to oxygen availability but also offer valuable information for optimizing its growth in industrial applications. This research sheds light on the adaptive mechanisms of this bacterium, providing a foundation for further exploration and potential applications in various fields.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11494915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350371","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}