mSystems最新文献

{"title":"Pan-genome-scale metabolic modeling of <i>Bacillus subtilis</i> reveals functionally distinct groups.","authors":"Maxwell Neal, William Brakewood, Michael Betenbaugh, Karsten Zengler","doi":"10.1128/msystems.00923-24","DOIUrl":"10.1128/msystems.00923-24","url":null,"abstract":"<p><p><i>Bacillus subtilis</i> is an important industrial and environmental microorganism known to occupy many niches and produce many compounds of interest. Although it is one of the best-studied organisms, much of this focus including the reconstruction of genome-scale metabolic models has been placed on a few key laboratory strains. Here, we substantially expand these prior models to pan-genome-scale, representing 481 genomes of <i>B. subtilis</i> with 2,315 orthologous gene clusters, 1,874 metabolites, and 2,239 reactions. Furthermore, we incorporate data from carbon utilization experiments for eight strains to refine and validate its metabolic predictions. This comprehensive pan-genome model enables the assessment of strain-to-strain differences related to nutrient utilization, fermentation outputs, robustness, and other metabolic aspects. Using the model and phenotypic predictions, we divide <i>B. subtilis</i> strains into five groups with distinct patterns of behavior that correlate across these features. The pan-genome model offers deep insights into <i>B. subtilis'</i> metabolism as it varies across environments and provides an understanding as to how different strains have adapted to dynamic habitats.</p><p><strong>Importance: </strong>As the volume of genomic data and computational power have increased, so has the number of genome-scale metabolic models. These models encapsulate the totality of metabolic functions for a given organism. <i>Bacillus subtilis</i> strain 168 is one of the first bacteria for which a metabolic network was reconstructed. Since then, several updated reconstructions have been generated for this model microorganism. Here, we expand the metabolic model for a single strain into a pan-genome-scale model, which consists of individual models for 481 <i>B. subtilis</i> strains. By evaluating differences between these strains, we identified five distinct groups of strains, allowing for the rapid classification of any particular strain. Furthermore, this classification into five groups aids the rapid identification of suitable strains for any application.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0092324"},"PeriodicalIF":5.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11575223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372285","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":"The ability in managing reactive oxygen species affects <i>Escherichia coli</i> persistence to ampicillin after nutrient shifts.","authors":"Ruixue Zhang, Christopher Hartline, Fuzhong Zhang","doi":"10.1128/msystems.01295-24","DOIUrl":"10.1128/msystems.01295-24","url":null,"abstract":"<p><p>Bacterial persistence profoundly impacts biofilms, infections, and antibiotic effectiveness. Persister formation can be substantially promoted by nutrient shift, which commonly exists in natural environments. However, mechanisms that promote persister formation remain poorly understood. Here, we investigated the persistence frequency of <i>Escherichia coli</i> after switching from various carbon sources to fatty acid and observed drastically different survival rates. While more than 99.9% of cells died during a 24-hour ampicillin (AMP) treatment after the glycerol to oleic acid (GLY → OA + AMP) shift, a surprising 56% of cells survived the same antibiotic treatment after the glucose to oleic acid (GLU → OOA + AMP) shift. Using a combination of single-cell imaging and time-lapse microscopy, we discovered that the induction of high levels of reactive oxygen species (ROS) by AMP is the primary mechanism of cell killing after switching from gluconeogenic carbons to OA + AMP. Moreover, the timing of the ROS burst is highly correlated (<i>R</i>² = 0.91) with the start of the rapid killing phase in the time-kill curves for all gluconeogenic carbons. However, ROS did not accumulate to lethal levels after the GLU → OA + AMP shift. We also found that the overexpression of the oxidative stress regulator and ROS detoxification enzymes strongly affects the amounts of ROS and the persistence frequency following the nutritional shift. These findings elucidate the different persister frequencies resulting from various nutrient shifts and underscore the pivotal role of ROS. Our study provides insights into bacterial persistence mechanisms, holding promise for targeted therapeutic interventions combating bacterial resistance effectively.</p><p><strong>Importance: </strong>This research delves into the intriguing realm of bacterial persistence and its profound implications for biofilms, infections, and antibiotic efficacy. The study focuses on <i>Escherichia coli</i> and how the switch from different carbon sources to fatty acids influences the formation of persister-resilient bacterial cells resistant to antibiotics. The findings reveal a striking variation in survival rates, with a significant number of cells surviving ampicillin treatment after transitioning from glucose to oleic acid. The key revelation is the role of reactive oxygen species (ROS) in cell killing, particularly after switching from gluconeogenic carbons. The timing of ROS bursts aligns with the rapid killing phase, highlighting the critical impact of oxidative stress regulation on persistence frequency. This research provides valuable insights into bacterial persistence mechanisms, offering potential avenues for targeted therapeutic interventions to combat bacterial resistance effectively.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0129524"},"PeriodicalIF":5.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11575164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522476","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":"Effect of combined probiotics and doxycycline therapy on the gut-skin axis in rosacea.","authors":"Jie Yu, Yan Duan, Meng Zhang, Qi Li, Miao Cao, Weixin Song, Feiyan Zhao, Lai-Yu Kwok, Heping Zhang, Ruiya Li, Zhihong Sun","doi":"10.1128/msystems.01201-24","DOIUrl":"10.1128/msystems.01201-24","url":null,"abstract":"<p><p>Rosacea is a chronic inflammatory skin condition marked by facial erythema, telangiectasia, and acne-like eruptions, affecting millions worldwide. While antibiotics remain a common treatment, prolonged use has significant adverse effects and can lead to antibiotic resistance. This study evaluated the impact of combined probiotics and doxycycline treatment on rosacea, emphasizing the gut-skin axis. Sixty rosacea patients were randomly assigned to the probiotic, placebo, or control groups. After a 2-week doxycycline treatment, participants underwent a 3-month intervention with either a placebo, probiotic, or no further treatment. Clinical outcomes were assessed at baseline and after the 14-week intervention. Our results showed that probiotic administration improved facial skin conditions, alleviated inflammation, and reduced facial skin microbiota diversity while enhancing gut microbiota heterogeneity. Multivariate analysis identified microbial markers distinguishing the probiotic group from the control and placebo groups, and some markers were associated with skin health parameters. After the probiotic intervention, some facial skin-associated taxa, such as <i>Aquabacterium</i> sp., <i>UBA4096</i> sp. 1, <i>UBA4096</i> sp. 2, and <i>Yimella indica</i>, decreased in abundance. Additionally, the fecal microbiota of the probiotic group was enriched in specific gut microbes, including <i>Streptococcus parasanguinis</i>, <i>Erysipelatoclostridium ramosum</i>, and <i>Coprobacillus cateniformis</i>, while showing a reduced abundance of <i>Bacteroides vulgatus</i>. These changes were associated with reduced facial sebum levels and a lower physician's global assessment score. Finally, fewer antibiotic resistance genes, particularly tetracycline resistance genes, were detected in the probiotic group compared with the control and placebo groups. Our study supports the existence of a gut-skin axis and the application of probiotics in managing rosacea.</p><p><strong>Importance: </strong>This research elucidates rosacea management with novel insights into probiotic use alongside doxycycline, showing dual benefits in symptom relief and inflammation reduction in patients. The study maps probiotic-induced shifts in gut and skin microbiota, underscoring microbial shifts correlating with skin health improvements. Crucially, it deciphers the gut-skin axis modulation by probiotics, proposing a method to curb antibiotic resistance in rosacea therapies. This study furnishes robust evidence for probiotics in rosacea, advancing our grasp of the gut-skin relationship.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0120124"},"PeriodicalIF":5.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11575305/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546356","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":"Multi-omics analysis reveals the core microbiome and biomarker for nutrition degradation in alfalfa silage fermentation.","authors":"Yuan Wang, Yunlei Sun, KeXin Huang, Yu Gao, Yufan Lin, Baojie Yuan, Xin Wang, Gang Xu, Luiz Gustavo Nussio, Fuyu Yang, Kuikui Ni","doi":"10.1128/msystems.00682-24","DOIUrl":"10.1128/msystems.00682-24","url":null,"abstract":"<p><p>Alfalfa (<i>Medicago sativa</i> L.) is one of the most extensively cultivated forage crops globally, and its nutritional quality critically influences the productivity of dairy cows. Silage fermentation is recognized as a crucial technique for the preservation of fresh forage, ensuring the retention of its vital nutrients. However, the detailed microbial components and their functions in silage fermentation are not fully understood. This study integrated large-scale microbial culturing with high-throughput sequencing to thoroughly examine the microbial community structure in alfalfa silage and explored the potential pathways of nutritional degradation via metagenomic analysis. The findings revealed an enriched microbial diversity in silage, indicated by the identification of amplicon sequence variants. Significantly, the large-scale culturing approach recovered a considerable number of unique microbes undetectable by high-throughput sequencing. Predominant genera, such as <i>Lactiplantibacillus</i>, <i>Leuconostoc</i>, <i>Lentilactobacillus</i>, <i>Weissella</i>, and <i>Liquorilactobacillus</i>, were identified based on their abundance and prevalence. Additionally, genes associated with Enterobacteriaceae were discovered, which might be involved in pathways leading to the production of ammonia-N and butyric acid. Overall, this study offers a comprehensive insight into the microbial ecology of silage fermentation and provides valuable information for leveraging microbial consortia to enhance fermentation quality.</p><p><strong>Importance: </strong>Silage fermentation is a microbial-driven anaerobic process that efficiently converts various substrates into nutrients readily absorbable and metabolizable by ruminant animals. This study, integrating culturomics and metagenomics, has successfully identified core microorganisms involved in silage fermentation, including those at low abundance. This discovery is crucial for the targeted cultivation of specific microorganisms to optimize fermentation processes. Furthermore, our research has uncovered signature microorganisms that play pivotal roles in nutrient metabolism, significantly advancing our understanding of the intricate relationships between microbial communities and nutrient degradation during silage fermentation.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0068224"},"PeriodicalIF":5.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11575373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504404","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":"Advancing microbiome research in Māori populations: insights from recent literature exploring the gut microbiomes of underrepresented and Indigenous peoples.","authors":"Ella T Silk, Simone B Bayer, Meika Foster, Nicole C Roy, Michael W Taylor, Tommi Vatanen, Richard B Gearry","doi":"10.1128/msystems.00909-24","DOIUrl":"10.1128/msystems.00909-24","url":null,"abstract":"<p><p>The gut microbiome plays vital roles in human health, including mediating metabolism, immunity, and the gut-brain axis. Many ethnicities remain underrepresented in gut microbiome research, with significant variation between Indigenous and non-Indigenous peoples due to dietary, socioeconomic, health, and urbanization differences. Although research regarding the microbiomes of Indigenous peoples is increasing, Māori microbiome literature is lacking despite widespread inequities that Māori populations face. These inequities likely contribute to gut microbiome differences that exacerbate negative health outcomes. Characterizing the gut microbiomes of underrepresented populations is necessary to inform efforts to address health inequities. However, for microbiome research to be culturally responsible and meaningful, study design must improve to better protect the rights and interests of Indigenous peoples. Here, we discuss barriers to Indigenous participation in research and the role disparities may play in shaping the gut microbiomes of Indigenous peoples, with a particular focus on implications for Māori and areas for improvement.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0090924"},"PeriodicalIF":5.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11575238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372284","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":"Transcriptomic and proteomic changes associated with cobalamin-dependent propionate production by the rumen bacterium <i>Xylanibacter ruminicola</i>.","authors":"Sam C Mahoney-Kurpe, Nikola Palevich, Dragana Gagic, Patrick J Biggs, Peter M Reid, Ianina Altshuler, Phillip B Pope, Graeme T Attwood, Christina D Moon","doi":"10.1128/msystems.00864-24","DOIUrl":"10.1128/msystems.00864-24","url":null,"abstract":"<p><p><i>Xylanibacter ruminicola</i> is an abundant rumen bacterium that produces propionate in a cobalamin (vitamin B₁₂)-dependent manner via the succinate pathway. However, the extent to which this occurs across ruminal <i>Xylanibacter</i> and closely related bacteria, and the effect of cobalamin supplementation on the expression of propionate pathway genes and enzymes has yet to be investigated. To assess this, we screened 14 strains and found that almost all strains produced propionate when supplemented with cobalamin. <i>X. ruminicola</i> KHP1 was selected for further study, including complete genome sequencing, and comparative transcriptomics and proteomics of KHP1 cultures grown with and without supplemented cobalamin. The complete KHP1 genome was searched for cobalamin-binding riboswitches and four were predicted, though none were closely located to any of the succinate pathway genes, which were dispersed at numerous genomic loci. Cobalamin supplementation led to the differential expression of 17.5% of genes, including genes encoding the cobalamin-dependent methylmalonyl-CoA mutase and some methylmalonyl-CoA decarboxylase subunits, but most propionate biosynthesis pathway genes were not differentially expressed. The effect of cobalamin supplementation on the KHP1 proteome was much less pronounced, with the only differentially abundant propionate pathway enzyme being methylmalonyl-CoA mutase, which had greater abundance when supplemented with cobalamin. Our results demonstrate that cobalamin supplementation does not result in induction of the entire propionate biosynthesis pathway, but consistently increased expression of methylmalonyl-CoA mutase at transcriptome and proteome levels. The magnitude of the differential expression of propionate pathway genes observed was minor compared to that of genes proximate to predicted cobalamin riboswitches.</p><p><strong>Importance: </strong>In ruminants, the rumen microbial community plays a critical role in nutrition through the fermentation of feed to provide vital energy substrates for the host animal. Propionate is a major rumen fermentation end-product and increasing its production is desirable given its importance in host glucose production and impact on greenhouse gas production. Vitamin B₁₂ (cobalamin) can induce propionate production in the prominent rumen bacterium <i>Xylanibacter ruminicola</i>, but it is not fully understood how cobalamin regulates propionate pathway activity. Contrary to expectation, we found that cobalamin supplementation had little effect on propionate pathway expression at transcriptome and proteome levels, with minor upregulation of genes encoding the cobalamin-dependent enzyme of the pathway. These findings provide new insights into factors that regulate propionate production and suggest that cobalamin-dependent propionate production by <i>X. ruminicola</i> is controlled post-translationally.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0086424"},"PeriodicalIF":5.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11575231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522477","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":"Microbial diversification is maintained in an experimentally evolved synthetic community.","authors":"Zahraa Al-Tameemi, Alejandra Rodríguez-Verdugo","doi":"10.1128/msystems.01053-24","DOIUrl":"10.1128/msystems.01053-24","url":null,"abstract":"<p><p>Microbial communities are incredibly diverse. Yet, the eco-evolutionary processes originating and maintaining this diversity remain understudied. Here, we investigate the patterns of diversification for <i>Pseudomonas putida</i> evolving in isolation and with <i>Acinetobacter johnsonii</i> leaking resources used by <i>P. putida</i>. We experimentally evolved four experimental replicates in monoculture and co-culture for 200 generations. We observed that <i>P. putida</i> diversified into two distinct morphotypes that differed from their ancestor by single-point mutations. One of the most prominent mutations hit the <i>fleQ</i> gene encoding the master regulator of flagella and biofilm formation. We experimentally confirmed that <i>fleQ</i> mutants were unable to swim and formed less biofilm than their ancestor, but they also produced higher yields. Interestingly, the <i>fleQ</i> genotype and other mutations swept to fixation in monocultures but not in co-cultures. In co-cultures, the two lineages stably coexisted for approximately 150 generations. We hypothesized that <i>A. johnsonii</i> modulates the coexistence of the two lineages through frequency-dependent selection. However, invasion experiments with two genotypes in monoculture and co-culture did not support this hypothesis. Finally, we conducted an evolutionary \"replay\" experiment to assess whether the presence or absence of <i>A. johnsonii</i> influenced the coexistence of morphotypes at the population level. Interestingly, <i>A. johnsonii</i> had a stabilizing effect on the co-culture. Overall, our study suggests that interspecies interactions play an important role in shaping patterns of diversification in microbial communities.</p><p><strong>Importance: </strong>In nature, bacteria live in microbial communities and interact with other species, for example, through the exchange of resources leaked into the external environment (i.e., cross-feeding interactions). The role that these cross-feeding interactions play in shaping patterns of diversification remains understudied. Using a simple bacterial system in which one species cross-feeds resources to a second species (commensal species), we showed that the commensal species diversified into two subpopulations that persisted only when the cross-feeder partner was present. We further observed loss-of-function mutations in flagellar genes that were fixed in monocultures but not in co-cultures. Our findings suggest that cross-feeding species influence patterns of diversification of other species. Given that nutrient leakage is pervasive in microbial communities, the findings from this study have the potential to extend beyond our specific bacterial system. Importantly, our study has contributed to answering the larger question of whether species evolved differently in isolation versus when interacting with other species.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0105324"},"PeriodicalIF":5.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11575400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470284","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":"NanoCore: core-genome-based bacterial genomic surveillance and outbreak detection in healthcare facilities from Nanopore and Illumina data.","authors":"Sebastian A Fuchs, Lisanna Hülse, Teresa Tamayo, Susanne Kolbe-Busch, Klaus Pfeffer, Alexander T Dilthey","doi":"10.1128/msystems.01080-24","DOIUrl":"10.1128/msystems.01080-24","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Genomic surveillance enables the early detection of pathogen transmission in healthcare facilities and contributes to the reduction of substantial patient harm. Fast turnaround times, flexible multiplexing, and low capital requirements make Nanopore sequencing well suited for genomic surveillance purposes; the analysis of Nanopore data, however, can be challenging. We present NanoCore, a user-friendly method for Nanopore-based genomic surveillance in healthcare facilities, enabling the calculation and visualization of cgMLST-like (core-genome multilocus sequence typing) sample distances directly from unassembled Nanopore reads. NanoCore implements a mapping, variant calling, and multilevel filtering strategy and also supports the analysis of Illumina data. We validated NanoCore on two 24-isolate data sets of methicillin-resistant &lt;i&gt;Staphylococcus aureus&lt;/i&gt; (MRSA) and vancomycin-resistant &lt;i&gt;Enterococcus faecium&lt;/i&gt; (VRE). In the Nanopore-only mode, NanoCore-based pairwise distances between closely related isolates were near-identical to Illumina-based SeqSphere&lt;sup&gt;+&lt;/sup&gt; distances, a gold standard commercial method (average differences of 0.75 and 0.81 alleles for MRSA and VRE; sd = 0.98 and 1.00), and gave an identical clustering into closely related and non-closely related isolates. In the \"hybrid\" mode, in which only Nanopore data are used for some isolates and only Illumina data for others, increased average pairwise isolate distance differences were observed (average differences of 3.44 and 1.95 for MRSA and VRE, respectively; sd = 2.76 and 1.34), while clustering results remained identical. NanoCore is computationally efficient (&lt;15 hours of wall time for the analysis of a 24-isolate data set on a workstation), available as free software, and supports installation via conda. In conclusion, NanoCore enables the effective use of the Nanopore technology for bacterial pathogen surveillance in healthcare facilities.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;Genomic surveillance involves sequencing the genomes and measuring the relatedness of bacteria from different patients or locations in the same healthcare facility, enabling an improved understanding of pathogen transmission pathways and the detection of \"silent\" outbreaks that would otherwise go undetected. It has become an indispensable tool for the detection and prevention of healthcare-associated infections and is routinely applied by many healthcare institutions. The earlier an outbreak or transmission chain is detected, the better; in this context, the Oxford Nanopore sequencing technology has important potential advantages over traditionally used short-read sequencing technologies, because it supports \"real-time\" data generation and the cost-effective \"on demand\" sequencing of small numbers of bacterial isolates. The analysis of Nanopore sequencing data, however, can be challenging. We present NanoCore, a user-friendly software for genomic surveillance that works directly based on N","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0108024"},"PeriodicalIF":5.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11575142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381283","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":"A temperature-induced metabolic shift in the emerging human pathogen <i>Photorhabdus asymbiotica</i>.","authors":"Elena Lucy Carter, Nicholas R Waterfield, Chrystala Constantinidou, Mohammad Tauqeer Alam","doi":"10.1128/msystems.00970-23","DOIUrl":"10.1128/msystems.00970-23","url":null,"abstract":"<p><p><i>Photorhabdus</i> is a bacterial genus containing both insect and emerging human pathogens. Most insect-restricted species display temperature restriction, unable to grow above 34°C, while <i>Photorhabdus asymbiotica</i> can grow at 37°C to infect mammalian hosts and cause Photorhabdosis. Metabolic adaptations have been proposed to facilitate the survival of this pathogen at higher temperatures, yet the biological mechanisms underlying these are poorly understood. We have reconstructed an extensively manually curated genome-scale metabolic model of <i>P. asymbiotica</i> (iEC1073, BioModels ID MODEL2309110001), validated through <i>in silico</i> gene knockout and nutrient utilization experiments with an excellent agreement between experimental data and model predictions. Integration of iEC1073 with transcriptomics data obtained for <i>P. asymbiotica</i> at temperatures of 28°C and 37°C allowed the development of temperature-specific reconstructions representing metabolic adaptations the pathogen undergoes when shifting to a higher temperature in a mammalian compared to insect host. Analysis of these temperature-specific reconstructions reveals that nucleotide metabolism is enriched with predicted upregulated and downregulated reactions. iEC1073 could be used as a powerful tool to study the metabolism of <i>P. asymbiotica,</i> in different genetic or environmental conditions.</p><p><strong>Importance: </strong><i>Photorhabdus</i> bacterial species contain both human and insect pathogens, and most of these species cannot grow in higher temperatures. However, <i>Photorhabdus asymbiotica</i>, which infects both humans and insects, can grow in higher temperatures and undergoes metabolic adaptations at a temperature of 37°C compared to that of insect body temperature. Therefore, it is important to examine how this bacterial species can metabolically adapt to survive in higher temperatures. In this work, using a mathematical model, we have examined the metabolic shift that takes place when the bacteria switch from growth conditions in 28°C to 37°C. We show that <i>P. asymbiotica</i> potentially experiences predicted temperature-induced metabolic adaptations at 37°C predominantly clustered within the nucleotide metabolism pathway.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0097023"},"PeriodicalIF":5.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11575385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504403","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":"Antimicrobial and antibiofilm activity of human recombinant H1 histones against bacterial infections.","authors":"Betsy Verónica Arévalo-Jaimes, Mónica Salinas-Pena, Inmaculada Ponte, Albert Jordan, Alicia Roque, Eduard Torrents","doi":"10.1128/msystems.00704-24","DOIUrl":"10.1128/msystems.00704-24","url":null,"abstract":"<p><p>Histones possess significant antimicrobial potential, yet their activity against biofilms remains underexplored. Moreover, concerns regarding adverse effects limit their clinical implementation. We investigated the antibacterial efficacy of human recombinant histone H1 subtypes against <i>Pseudomonas aeruginosa</i> PAO1, both planktonic and in biofilms. After the <i>in vitro</i> tests, toxicity and efficacy were assessed in a <i>P. aeruginosa</i> PAO1 infection model using <i>Galleria mellonella</i> larvae. Histones were also evaluated in combination with ciprofloxacin (Cpx) and gentamicin (Gm). Our results demonstrate antimicrobial activity of all three histones against <i>P. aeruginosa</i> PAO1, with H1.0 and H1.4 showing efficacy at lower concentrations. The bactericidal effect was associated with a mechanism of membrane disruption. <i>In vitro</i> studies using static and dynamic models showed that H1.4 had antibiofilm potential by reducing cell biomass. Neither H1.0 nor H1.4 showed toxicity in <i>G. mellonella</i> larvae, and both increased larvae survival when infected with <i>P. aeruginosa</i> PAO1. Although <i>in vitro</i> synergism was observed between ciprofloxacin and H1.0, no improvement over the antibiotic alone was noted <i>in vivo</i>. Differences in antibacterial and antibiofilm activity were attributed to sequence and structural variations among histone subtypes. Moreover, the efficacy of H1.0 and H1.4 was influenced by the presence and strength of the extracellular matrix. These findings suggest histones hold promise for combating acute and chronic infections caused by pathogens such as <i>P. aeruginosa</i>.IMPORTANCEThe constant increase of multidrug-resistant bacteria is a critical global concern. The inefficacy of current therapies to treat bacterial infections is attributed to multiple mechanisms of resistance, including the capacity to form biofilms. Therefore, the identification of novel and safe therapeutic strategies is imperative. This study confirms the antimicrobial potential of three histone H1 subtypes against both Gram-negative and Gram-positive bacteria. Furthermore, histones H1.0 and H1.4 demonstrated <i>in vivo</i> efficacy without associated toxicity in an acute infection model of <i>Pseudomonas aeruginosa</i> PAO1 in <i>Galleria mellonella</i> larvae. The bactericidal effect of these proteins also resulted in biomass reduction of <i>P. aeruginosa</i> PAO1 biofilms. Given the clinical significance of this opportunistic pathogen, our research provides a comprehensive initial evaluation of the efficacy, toxicity, and mechanism of action of a potential new therapeutic approach against acute and chronic bacterial infections.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0070424"},"PeriodicalIF":5.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11575268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522473","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}