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Whole-genome sequencing for antimicrobial surveillance: species-specific quality thresholds and data evaluation from the network of the European Union Reference Laboratory for Antimicrobial Resistance genomic proficiency tests of 2021 and 2022. 用于抗菌素监测的全基因组测序:2021 年和 2022 年欧盟抗菌素耐药性参考实验室基因组能力测试网络的特定物种质量阈值和数据评估。
IF 5 2区 生物学
mSystems Pub Date : 2024-09-17 Epub Date: 2024-08-06 DOI: 10.1128/msystems.00160-24
Lauge Holm Sørensen, Susanne Karlsmose Pedersen, Jacob Dyring Jensen, Niamh Lacy-Roberts, Athina Andrea, Michael S M Brouwer, Kees T Veldman, Yan Lou, Maria Hoffmann, Rene S Hendriksen
{"title":"Whole-genome sequencing for antimicrobial surveillance: species-specific quality thresholds and data evaluation from the network of the European Union Reference Laboratory for Antimicrobial Resistance genomic proficiency tests of 2021 and 2022.","authors":"Lauge Holm Sørensen, Susanne Karlsmose Pedersen, Jacob Dyring Jensen, Niamh Lacy-Roberts, Athina Andrea, Michael S M Brouwer, Kees T Veldman, Yan Lou, Maria Hoffmann, Rene S Hendriksen","doi":"10.1128/msystems.00160-24","DOIUrl":"10.1128/msystems.00160-24","url":null,"abstract":"<p><p>As antimicrobial resistance (AMR) surveillance shifts to genomics, ensuring the quality of whole-genome sequencing (WGS) data produced across laboratories is critical. Participation in genomic proficiency tests (GPTs) not only increases individual laboratories' WGS capacity but also provides a unique opportunity to improve species-specific thresholds for WGS quality control (QC) by repeated resequencing of distinct isolates. Here, we present the results of the EU Reference Laboratory for Antimicrobial Resistance (EURL-AR) network GPTs of 2021 and 2022, which included 25 EU national reference laboratories (NLRs). A total of 392 genomes from 12 AMR-bacteria were evaluated based on WGS QC metrics. Two percent (<i>n</i> = 9) of the data were excluded, due to contamination, and 11% (<i>n</i> = 41) of the remaining genomes were identified as outliers in at least one QC metric and excluded from computation of the adjusted QC thresholds (AQT). Two QC metric correlation groups were identified through linear regression. Eight percent (<i>n</i> = 28) of the submitted genomes, from 11 laboratories, failed one or more of the AQTs. However, only three laboratories (12%) were identified as underperformers, failing across AQTs for uncorrelated QC metrics in at least two genomes. Finally, new species-specific thresholds for \"N50\" and \"number of contigs > 200 bp\" are presented for guidance in routine laboratory QC. The continued participation of NRLs in GPTs will reveal WGS workflow flaws and improve AMR surveillance data. GPT data will continue to contribute to the development of reliable species-specific thresholds for routine WGS QC, standardizing sequencing data QC and ensure inter- and intranational laboratory comparability.IMPORTANCEIllumina next-generation sequencing is an integral part of antimicrobial resistance (AMR) surveillance and the most widely used whole-genome sequencing (WGS) platform. The high-throughput, relative low-cost, high discriminatory power, and rapid turnaround time of WGS compared to classical biochemical methods means the technology will likely remain a fundamental tool in AMR surveillance and public health. In this study, we present the current level of WGS capacity among national reference laboratories in the EU Reference Laboratory for AMR network, summarizing applied methodology and statistically evaluating the quality of the obtained sequence data. These findings provide the basis for setting new and revised thresholds for quality metrics used in routine WGS, which have previously been arbitrarily defined. In addition, underperforming participants are identified and encouraged to evaluate their workflows to produce reliable results.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0016024"},"PeriodicalIF":5.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11406893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893844","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}
引用次数: 0
Ruminal microbial metagenomes and host transcriptomes shed light on individual variability in the growth rate of lambs before weaning: the regulated mechanism and potential long-term effect on the host. 反刍微生物元基因组和宿主转录组揭示了羔羊断奶前生长速度的个体差异:调节机制和对宿主的潜在长期影响。
IF 5 2区 生物学
mSystems Pub Date : 2024-09-17 Epub Date: 2024-08-20 DOI: 10.1128/msystems.00873-24
Fan Hu, Yan Cheng, Bing Fan, Wei Li, Bingsen Ye, Zhiwu Wu, Zhiliang Tan, Zhixiong He
{"title":"Ruminal microbial metagenomes and host transcriptomes shed light on individual variability in the growth rate of lambs before weaning: the regulated mechanism and potential long-term effect on the host.","authors":"Fan Hu, Yan Cheng, Bing Fan, Wei Li, Bingsen Ye, Zhiwu Wu, Zhiliang Tan, Zhixiong He","doi":"10.1128/msystems.00873-24","DOIUrl":"10.1128/msystems.00873-24","url":null,"abstract":"<p><p>Weaning weight is a reflection of management during the breastfeeding phase and will influence animal performance in subsequent phases, considered important indicators within production systems. The aims of this study were as follows: (i) to investigate variability in the growth rate among individual lambs from ewes rearing single or twin lambs fed with two different diets and (ii) to explore the molecular mechanisms regulating the growth rate and the potential long-term effects on the host. No significant change in lamb average daily gain (ADG) was observed in litter size and diet treatment, and there were large variations among individual lambs (ranging from 0.13 to 0.41 kg/day). Further analysis was conducted on serum amino acids, rumen fermentation characteristics, rumen metagenomics and transcriptome, and hepatic transcriptome of lambs with extremely high (HA; <i>n</i> = 6) and low (LA; <i>n</i> = 6) ADG. We observed significant increases in serum lysine, leucine, alanine, and phenylalanine in the HA group. The metagenome revealed that the HA group presented a higher rumen propionate molar proportion via increasing gene abundance in the succinate pathway for propionate synthesis. For the rumen transcriptome, higher expressed gene sets in the HA group were mainly related to rumen epithelial growth, including cytokine-cytokine receptor interaction, Jak-STAT signaling pathway, and adherens junction. For the liver transcriptome, the upregulated KEGG pathways in the HA group were primarily associated with fatty acid degradation, glyoxylate and dicarboxylate metabolism, cholesterol metabolism, and the immune system. This research suggests that preweaning lambs with high ADG may benefit from rumen development and enhanced liver metabolic and immune function.</p><p><strong>Importance: </strong>There is accumulating evidence indicating that the early-life rumen microbiome plays vital roles in rumen development and microbial fermentation, which subsequently affects the growth of young ruminants. The liver is also vital to regulate the metabolism and distribution of nutrients. Our results demonstrate that lambs with high average daily gain (ADG) enhanced microbial volatile fatty acid (VFA) metabolism toward rumen propionate and serum amino acid (AA) production to support host growth. The study highlights that high ADG in the preweaning period is beneficial for the rumen development and liver energy metabolism, leading to better growth later in life. Overall, this study explores the molecular mechanisms regulating the growth rate and the potential long-term effects of increased growth rate on the host metabolism, providing fundamental knowledge about nutrient manipulation in pre-weaning.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0087324"},"PeriodicalIF":5.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11406974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142004847","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}
引用次数: 0
Antibacterial effect of phage cocktails and phage-antibiotic synergy against pathogenic Klebsiella pneumoniae. 噬菌体鸡尾酒和噬菌体-抗生素协同作用对致病性肺炎克雷伯氏菌的抗菌效果。
IF 5 2区 生物学
mSystems Pub Date : 2024-09-17 Epub Date: 2024-08-21 DOI: 10.1128/msystems.00607-24
Mengshi Zhao, Hongru Li, Dehao Gan, Mengzhu Wang, Hui Deng, Qiu E Yang
{"title":"Antibacterial effect of phage cocktails and phage-antibiotic synergy against pathogenic <i>Klebsiella pneumoniae</i>.","authors":"Mengshi Zhao, Hongru Li, Dehao Gan, Mengzhu Wang, Hui Deng, Qiu E Yang","doi":"10.1128/msystems.00607-24","DOIUrl":"10.1128/msystems.00607-24","url":null,"abstract":"<p><p>The global rise of antibiotic resistance has renewed interest in phage therapy, as an alternative to antibiotics to eliminate multidrug-resistant (MDR) bacterial pathogens. However, optimizing the broad-spectrum efficacy of phage therapy remains a challenge. In this study, we addressed this issue by employing strategies to improve antimicrobial efficacy of phage therapy against MDR <i>Klebsiella pneumoniae</i> strains, which are notorious for their resistance to conventional antibiotics. This includes the selection of broad host range phages, optimization of phage formulation, and combinations with last-resort antibiotics. Our findings unveil that having a broad host range was a dominant trait of isolated phages, and increasing phage numbers in combination with antibiotics significantly enhanced the suppression of bacterial growth. The decreased incidence of bacterial infection was explained by a reduction in pathogen density and emergence of bacterial resistance. Furthermore, phage-antibiotic synergy (PAS) demonstrated considerable broad-spectrum antibacterial potential against different clades of clinical MDR <i>K. pneumoniae</i> pathogens. The improved treatment outcomes of optimized PAS were also evident in a murine model, where mice receiving optimized PAS therapy demonstrated a reduced bacterial burden in mouse tissues. Taken together, these findings offer an important development in optimizing PAS therapy and its efficacy in the elimination of MDR <i>K. pneumoniae</i> pathogens.</p><p><strong>Importance: </strong>The worldwide spread of antimicrobial resistance (AMR) has posed a great challenge to global public health. Phage therapy has become a promising alternative against difficult-to-treat pathogens. One important goal of this study was to optimize the therapeutic efficiency of phage-antibiotic combinations, known as phage-antibiotic synergy (PAS). Through comprehensive analysis of the phenotypic and genotypic characteristics of a large number of CRKp-specific phages, we developed a systematic model for phage cocktail combinations. Crucially, our finding demonstrated that PAS treatments not only enhance the bactericidal effects of colistin and tigecycline against multidrug-resistant (MDR) <i>K. pneumoniae</i> strains in <i>in vitro</i> and <i>in vivo</i> context but also provide a robust response when antibiotics fail. Overall, the optimized PAS therapy demonstrates considerable potential in combating diverse <i>K. pneumoniae</i> pathogens, highlighting its relevance as a strategy to mitigate antibiotic resistance threats effectively.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0060724"},"PeriodicalIF":5.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11406915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018068","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}
引用次数: 0
Gut dysbiosis contributes to the development of Budd-Chiari syndrome through immune imbalance. 肠道菌群失调会导致免疫失衡,从而引发巴德-恰里综合征。
IF 5 2区 生物学
mSystems Pub Date : 2024-09-17 Epub Date: 2024-08-21 DOI: 10.1128/msystems.00794-24
Qinwei Lu, Rongtao Zhu, Lin Zhou, Ruifang Zhang, Zhen Li, Peng Xu, Zhiwei Wang, Gang Wu, Jianzhuang Ren, Dechao Jiao, Yan Song, Jian Li, Weijie Wang, Ruopeng Liang, Xiuxian Ma, Yuling Sun
{"title":"Gut dysbiosis contributes to the development of Budd-Chiari syndrome through immune imbalance.","authors":"Qinwei Lu, Rongtao Zhu, Lin Zhou, Ruifang Zhang, Zhen Li, Peng Xu, Zhiwei Wang, Gang Wu, Jianzhuang Ren, Dechao Jiao, Yan Song, Jian Li, Weijie Wang, Ruopeng Liang, Xiuxian Ma, Yuling Sun","doi":"10.1128/msystems.00794-24","DOIUrl":"10.1128/msystems.00794-24","url":null,"abstract":"<p><p>Budd-Chiari syndrome (B-CS) is a rare and lethal condition characterized by hepatic venous outflow tract blockage. Gut microbiota has been linked to numerous hepatic disorders, but its significance in B-CS pathogenesis is uncertain. First, we performed a case-control study (<i>N</i><sub>case</sub> = 140, <i>N</i><sub>control</sub> = 63) to compare the fecal microbiota of B-CS and healthy individuals by metagenomics sequencing. B-CS patients' gut microbial composition and activity changed significantly, with a different metagenomic makeup, increased potentially pathogenic bacteria, including <i>Prevotella</i>, and disease-linked microbial function. Imbalanced cytokines in patients were demonstrated to be associated with gut dysbiosis, which led us to suspect that B-CS is associated with gut microbiota and immune dysregulation. Next, 16S ribosomal DNA sequencing on fecal microbiota transplantation (FMT) mice models examined the link between gut dysbiosis and B-CS. FMT models showed damaged liver tissues, posterior inferior vena cava, and increased <i>Prevotella</i> in the disturbed gut microbiota of FMT mice. Notably, B-CS-FMT impaired the morphological structure of colonic tissues and increased intestinal permeability. Furthermore, a significant increase of the same cytokines (IL-5, IL-6, IL-9, IL-10, IL-17A, IL-17F, and IL-13) and endotoxin levels in B-CS-FMT mice were observed. Our study suggested that gut microbial dysbiosis may cause B-CS through immunological dysregulation.</p><p><strong>Importance: </strong>This study revealed that gut microbial dysbiosis may cause Budd-Chiari syndrome (B-CS). Gut dysbiosis enhanced intestinal permeability, and toxic metabolites and imbalanced cytokines activated the immune system. Consequently, the escalation of causative factors led to their concentration in the portal vein, thereby compromising both the liver parenchyma and outflow tract. Therefore, we proposed that gut microbial dysbiosis induced immune imbalance by chronic systemic inflammation, which contributed to the B-CS development. Furthermore, <i>Prevotella</i> may mediate inflammation development and immune imbalance, showing potential in B-CS pathogenesis.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0079424"},"PeriodicalIF":5.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11406926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018071","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}
引用次数: 0
Novel isolates of hydrogen-oxidizing chemolithoautotrophic Sulfurospirillum provide insight to the functions and adaptation mechanisms of Campylobacteria in shallow-water hydrothermal vents. 新分离的氢氧化化学溶解自养型硫螺旋体为了解浅水热液喷口弯曲杆菌的功能和适应机制提供了启示。
IF 5 2区 生物学
mSystems Pub Date : 2024-09-17 Epub Date: 2024-08-21 DOI: 10.1128/msystems.00148-24
Li Wang, Xinyi Cheng, Yizhe Guo, Junwei Cao, Mingye Sun, Jiang-Shiou Hwang, Rulong Liu, Jiasong Fang
{"title":"Novel isolates of hydrogen-oxidizing chemolithoautotrophic <i>Sulfurospirillum</i> provide insight to the functions and adaptation mechanisms of Campylobacteria in shallow-water hydrothermal vents.","authors":"Li Wang, Xinyi Cheng, Yizhe Guo, Junwei Cao, Mingye Sun, Jiang-Shiou Hwang, Rulong Liu, Jiasong Fang","doi":"10.1128/msystems.00148-24","DOIUrl":"10.1128/msystems.00148-24","url":null,"abstract":"<p><p>Enhancing the availability of representative isolates from hydrothermal vents (HTVs) is imperative for comprehending the microbial processes that propel the vent ecosystem. In recent years, Campylobacteria have emerged as the predominant and ubiquitous taxon across both shallow and deep-sea vent systems. Nevertheless, only a few isolates have been cultured, primarily originating from deep-sea HTVs. Presently, no cultivable isolates of Campylobacteria are accessible in shallow water vent systems (<200 m), which exhibit markedly distinct environmental conditions from their deep-sea counterparts. In this study, we enriched a novel isolate (genus <i>Sulfurospirillum</i>, Campylobacteria) from shallow-water HTVs of Kueishan Island. Genomic and physiological analysis revealed that this novel Campylobacteria species grows on a variety of substrate and carbon/energy sources. The pan-genome and phenotypic comparisons with 12 previously isolated <i>Sulfurospirillum</i> species from different environments supported the identification of functional features in <i>Sulfurospirillum</i> genomes crucial for adaptation to vent environments, such as sulfur oxidation, carbon fixation, biofilm formation, and benzoate/toluene degradation, as well as diverse genes related with signal transportation. To conclude, the metabolic characteristics of this novel Campylobacteria augment our understanding of Campylobacteria spanning from deep-sea to shallow-water vent systems.IMPORTANCECampylobacteria emerge as the dominant and ubiquitous taxa within vent systems, playing important roles in the vent ecosystems. However, isolated representatives of Campylobacteria have been mainly from the deep-sea hydrothermal fields, leaving a significant knowledge gap regarding the functions, activities, and adaptation strategies of the vent microorganisms in shallow-water hydrothermal vents (HTVs). This study bridges this gap by providing insights into the phenomics and genomic diversity of genus <i>Sulfurospirillum</i> (order Campylobacterales, class Campylobacteria) based on data derived from a novel isolate obtained from shallow-water HTVs. Our mesophilic isolate of <i>Sulfurospirillum</i> not only augments the genus diversity of Campylobacteria pure cultures derived from vent systems but also serves as the inaugural reference isolate for Campylobacteria in shallow-water environments.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0014824"},"PeriodicalIF":5.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11406935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018073","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}
引用次数: 0
Diverse non-canonical electron bifurcating [FeFe]-hydrogenases of separate evolutionary origins in Hydrogenedentota. 水螅中不同进化起源的多种非经典电子分叉[FeFe]-氢酶。
IF 5 2区 生物学
mSystems Pub Date : 2024-09-17 Epub Date: 2024-08-27 DOI: 10.1128/msystems.00999-24
Xiaowei Zheng, Li Huang
{"title":"Diverse non-canonical electron bifurcating [FeFe]-hydrogenases of separate evolutionary origins in <i>Hydrogenedentota</i>.","authors":"Xiaowei Zheng, Li Huang","doi":"10.1128/msystems.00999-24","DOIUrl":"10.1128/msystems.00999-24","url":null,"abstract":"<p><p><i>Hydrogenedentota</i>, a globally distributed bacterial phylum-level lineage, is poorly understood. Here, we established a comprehensive genomic catalog of <i>Hydrogenedentota</i>, including a total of seven clades (or families) with 179 genomes, and explored the metabolic potential and evolutionary history of these organisms. We show that a single genome, especially those belonging to Clade 6, often encodes multiple hydrogenases with genomes in Clade 2, which rarely encode hydrogenases being the exception. Notably, most members of <i>Hydrogenedentota</i> contain a group A3 [FeFe]-hydrogenase (BfuABC) with a non-canonical electron bifurcation mechanism, in addition to substrate-level phosphorylation and electron transport-linked phosphorylation pathways, in energy conservation. Furthermore, we show that BfuABC from <i>Hydrogenedentota</i> fall into five sub-types. Phylogenetic analysis reveals five independent routes for the evolution of BfuABC homologs in <i>Hydrogenedentota</i>. We speculate that the five sub-types of BfuABC might be acquired from <i>Bacillota</i> (synonym <i>Firmicutes</i>) through separate horizontal gene transfer events. These data shed light on the diversity and evolution of bifurcating [FeFe]-hydrogenases and provide insight into the strategy of <i>Hydrogenedentota</i> to adapt to survival in various habitats.</p><p><strong>Importance: </strong>The phylum <i>Hydrogenedentota</i> is widely distributed in various environments. However, their physiology, ecology, and evolutionary history remain unknown, primarily due to the limited availability of the genomes and the lack of cultured representatives of the phylum. Our results have increased the knowledge of the genetic and metabolic diversity of these organisms and shed light on their diverse energy conservation strategies, especially those involving electron bifurcation with a non-canonical mechanism, which are likely responsible for their wide distribution. Besides, the organization and phylogenetic relationships of gene clusters coding for BfuABC in <i>Hydrogenedentota</i> provide valuable clues to the evolutionary history of group A3 electron bifurcating [FeFe]-hydrogenases.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0099924"},"PeriodicalIF":5.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11406978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073268","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}
引用次数: 0
Interspecies synergistic interactions mediated by cofactor exchange enhance stress tolerance by inducing biofilm formation. 由辅助因子交换介导的种间协同作用通过诱导生物膜的形成增强了应激耐受性。
IF 5 2区 生物学
mSystems Pub Date : 2024-09-17 Epub Date: 2024-08-27 DOI: 10.1128/msystems.00884-24
Lvjing Wang, Xiaoyu Wang, Hao Wu, Haixia Wang, Zhenmei Lu
{"title":"Interspecies synergistic interactions mediated by cofactor exchange enhance stress tolerance by inducing biofilm formation.","authors":"Lvjing Wang, Xiaoyu Wang, Hao Wu, Haixia Wang, Zhenmei Lu","doi":"10.1128/msystems.00884-24","DOIUrl":"10.1128/msystems.00884-24","url":null,"abstract":"<p><p>Metabolic exchange plays a crucial role in shaping microbial community interactions and functions, including the exchange of small molecules such as cofactors. Cofactors are fundamental to enzyme catalytic activities; however, the role of cofactors in microbial stress tolerance is unclear. Here, we constructed a synergistic consortium containing two strains that could efficiently mineralize di-(2-ethylhexyl) phthalate under hyperosmotic stress. Integration of transcriptomic analysis, metabolic profiling, and a genome-scale metabolic model (GEM) facilitated the discovery of the potential mechanism of microbial interactions. Multi-omics analysis revealed that the vitamin B<sub>12</sub>-dependent methionine-folate cycle could be a key pathway for enhancing the hyperosmotic stress tolerance of synergistic consortium. Further GEM simulations revealed interspecies exchange of S-adenosyl-L-methionine and riboflavin, cofactors needed for vitamin B<sub>12</sub> biosynthesis, which was confirmed by <i>in vitro</i> experiments. Overall, we proposed a new mechanism of bacterial hyperosmotic stress tolerance: bacteria might promote the production of vitamin B<sub>12</sub> to enhance biofilm formation, and the species collaborate with each other by exchanging cofactors to improve consortium hyperosmotic stress tolerance. These findings offer new insights into the role of cofactors in microbial interactions and stress tolerance and are potentially exploitable for environmental remediation.</p><p><strong>Importance: </strong>Metabolic interactions (also known as cross-feeding) are thought to be ubiquitous in microbial communities. Cross-feeding is the basis for many positive interactions (e.g., mutualism) and is a primary driver of microbial community assembly. In this study, a combination of multi-omics analysis and metabolic modeling simulation was used to reveal the metabolic interactions of a synthetic consortium under hyperosmotic stress. Interspecies cofactor exchange was found to promote biofilm formation under hyperosmotic stress. This provides a new perspective for understanding the role of metabolic interactions in microbial communities to enhance environmental adaptation, which is significant for improving the efficiency of production activities and environmental bioremediation.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0088424"},"PeriodicalIF":5.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11406921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073270","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}
引用次数: 0
Food-breastmilk combinations alter the colonic microbiome of weaning infants: an in silico study. 食物-母乳组合改变断奶婴儿的结肠微生物群:一项模拟研究。
IF 5 2区 生物学
mSystems Pub Date : 2024-09-17 Epub Date: 2024-08-27 DOI: 10.1128/msystems.00577-24
Vitor G da Silva, Nick W Smith, Jane A Mullaney, Clare Wall, Nicole C Roy, Warren C McNabb
{"title":"Food-breastmilk combinations alter the colonic microbiome of weaning infants: an <i>in silico</i> study.","authors":"Vitor G da Silva, Nick W Smith, Jane A Mullaney, Clare Wall, Nicole C Roy, Warren C McNabb","doi":"10.1128/msystems.00577-24","DOIUrl":"10.1128/msystems.00577-24","url":null,"abstract":"<p><p>The introduction of solid foods to infants, also known as weaning, is a critical point for the development of the complex microbial community inhabiting the human colon, impacting host physiology in infancy and later in life. This research investigated <i>in silico</i> the impact of food-breastmilk combinations on growth and metabolite production by colonic microbes of New Zealand weaning infants using the metagenome-scale metabolic model named Microbial Community. Eighty-nine foods were individually combined with breastmilk, and the 12 combinations with the strongest influence on the microbial production of short-chain fatty acids (SCFAs) and branched-chain fatty acids (BCFAs) were identified. Fiber-rich and polyphenol-rich foods, like pumpkin and blackcurrant, resulted in the greatest increase in predicted fluxes of total SCFAs and individual fluxes of propionate and acetate when combined, respectively, with breastmilk. Identified foods were further combined with other foods and breastmilk, resulting in 66 multiple food-breastmilk combinations. These combinations altered <i>in silico</i> the impact of individual foods on the microbial production of SCFAs and BCFAs, suggesting that the interaction between the dietary compounds composing a meal is the key factor influencing colonic microbes. Blackcurrant combined with other foods and breastmilk promoted the greatest increase in the production of acetate and total SCFAs, while pork combined with other foods and breastmilk decreased the production of total BCFAs.IMPORTANCELittle is known about the influence of complementary foods on the colonic microbiome of weaning infants. Traditional <i>in vitro</i> and <i>in vivo</i> microbiome methods are limited by their resource-consuming concerns. Modeling approaches represent a promising complementary tool to provide insights into the behavior of microbial communities. This study evaluated how foods combined with other foods and human milk affect the production of short-chain fatty acids and branched-chain fatty acids by colonic microbes of weaning infants using a rapid and inexpensive <i>in silico</i> approach. Foods and food combinations identified here are candidates for future experimental investigations, helping to fill a crucial knowledge gap in infant nutrition.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0057724"},"PeriodicalIF":5.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11406890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080909","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}
引用次数: 0
In vivo fitness of sul gene-dependent sulfonamide-resistant Escherichia coli in the mammalian gut. 哺乳动物肠道中依赖磺胺基因的耐磺胺大肠杆菌的体内适应性。
IF 5 2区 生物学
mSystems Pub Date : 2024-09-17 Epub Date: 2024-08-14 DOI: 10.1128/msystems.00836-24
Han Jiang, Yuzhi Dong, Xue Jiao, Biao Tang, Tao Feng, Ping Li, Jiehong Fang
{"title":"<i>In vivo</i> fitness of <i>sul</i> gene-dependent sulfonamide-resistant <i>Escherichia coli</i> in the mammalian gut.","authors":"Han Jiang, Yuzhi Dong, Xue Jiao, Biao Tang, Tao Feng, Ping Li, Jiehong Fang","doi":"10.1128/msystems.00836-24","DOIUrl":"10.1128/msystems.00836-24","url":null,"abstract":"<p><p>The widespread sulfonamide resistance genes <i>sul1</i>, <i>sul2</i>, and <i>sul3</i> in food and gut bacteria have attracted considerable attention. In this study, we assessed the <i>in vivo</i> fitness of <i>sul</i> gene-dependent sulfonamide-resistant <i>Escherichia coli</i>, using a murine model. High fitness costs were incurred for <i>sul1</i> and <i>sul3</i> gene-dependent <i>E. coli</i> strains <i>in vivo</i>. A fitness advantage was found in three of the eight mice after intragastric administration of <i>sul2</i> gene-dependent <i>E. coli</i> strains. We isolated three compensatory mutant strains (CMSs) independently from three mice that outcompeted the parent strain P2 <i>in vivo</i>. Whole-genome sequencing revealed seven identical single nucleotide polymorphism (SNP) mutations in the three CMSs compared with strain P2, an additional SNP mutation in strain S2-2, and two additional SNP mutations in strain S2-3. Furthermore, tandem mass tag-based quantitative proteomic analysis revealed abundant differentially expressed proteins (DEPs) in the CMSs compared with P2. Of these, seven key fitness-related DEPs distributed in two-component systems, galactose and tryptophan metabolism pathways, were verified using parallel reaction monitoring analysis. The DEPs in the CMSs influenced bacterial motility, environmental stress tolerance, colonization ability, carbohydrate utilization, cell morphology maintenance, and chemotaxis to restore fitness costs and adapt to the mammalian gut environment.IMPORTANCESulfonamides are traditional synthetic antimicrobial agents used in clinical and veterinary medical settings. Their long-term excessive overuse has resulted in widespread microbial resistance, limiting their application for medical interventions. Resistance to sulfonamides is primarily conferred by the alternative genes <i>sul1</i>, <i>sul2</i>, and <i>sul3</i> encoding dihydropteroate synthase in bacteria. Studying the potential fitness cost of these <i>sul</i> genes is crucial for understanding the evolution and transmission of sulfonamide-resistant bacteria. <i>In vitro</i> studies have been conducted on the fitness cost of <i>sul</i> genes in bacteria. In this study, we provide critical insights into bacterial adaptation and transmission using an <i>in vivo</i> approach.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0083624"},"PeriodicalIF":5.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11406977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141976155","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}
引用次数: 0
Gut microbiota metabolically mediate intestinal helminth infection in zebrafish. 肠道微生物群在代谢上介导斑马鱼的肠道蠕虫感染。
IF 5 2区 生物学
mSystems Pub Date : 2024-09-17 Epub Date: 2024-08-27 DOI: 10.1128/msystems.00545-24
Austin J Hammer, Christopher A Gaulke, Manuel Garcia-Jaramillo, Connor Leong, Jeffrey Morre, Michael J Sieler, Jan F Stevens, Yuan Jiang, Claudia S Maier, Michael L Kent, Thomas J Sharpton
{"title":"Gut microbiota metabolically mediate intestinal helminth infection in zebrafish.","authors":"Austin J Hammer, Christopher A Gaulke, Manuel Garcia-Jaramillo, Connor Leong, Jeffrey Morre, Michael J Sieler, Jan F Stevens, Yuan Jiang, Claudia S Maier, Michael L Kent, Thomas J Sharpton","doi":"10.1128/msystems.00545-24","DOIUrl":"10.1128/msystems.00545-24","url":null,"abstract":"<p><p>Intestinal helminth parasite (IHP) infection induces alterations in the composition of microbial communities across vertebrates, although how gut microbiota may facilitate or hinder parasite infection remains poorly defined. In this work, we utilized a zebrafish model to investigate the relationship between gut microbiota, gut metabolites, and IHP infection. We found that extreme disparity in zebrafish parasite infection burden is linked to the composition of the gut microbiome and that changes in the gut microbiome are associated with variation in a class of endogenously produced signaling compounds, N-acylethanolamines, that are known to be involved in parasite infection. Using a statistical mediation analysis, we uncovered a set of gut microbes whose relative abundance explains the association between gut metabolites and infection outcomes. Experimental investigation of one of the compounds in this analysis reveals salicylaldehyde, which is putatively produced by the gut microbe <i>Pelomonas</i>, as a potent anthelmintic with activity against <i>Pseudocapillaria tomentosa</i> egg hatching, both <i>in vitro</i> and <i>in vivo</i>. Collectively, our findings underscore the importance of the gut microbiome as a mediating agent in parasitic infection and highlight specific gut metabolites as tools for the advancement of novel therapeutic interventions against IHP infection.</p><p><strong>Importance: </strong>Intestinal helminth parasites (IHPs) impact human health globally and interfere with animal health and agricultural productivity. While anthelmintics are critical to controlling parasite infections, their efficacy is increasingly compromised by drug resistance. Recent investigations suggest the gut microbiome might mediate helminth infection dynamics. So, identifying how gut microbes interact with parasites could yield new therapeutic targets for infection prevention and management. We conducted a study using a zebrafish model of parasitic infection to identify routes by which gut microbes might impact helminth infection outcomes. Our research linked the gut microbiome to both parasite infection and to metabolites in the gut to understand how microbes could alter parasite infection. We identified a metabolite in the gut, salicylaldehyde, that is putatively produced by a gut microbe and that inhibits parasitic egg growth. Our results also point to a class of compounds, N-acyl-ethanolamines, which are affected by changes in the gut microbiome and are linked to parasite infection. Collectively, our results indicate the gut microbiome may be a source of novel anthelmintics that can be harnessed to control IHPs.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0054524"},"PeriodicalIF":5.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11406965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080910","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}
引用次数: 0
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