mSystems最新文献

{"title":"Ecological drivers of CRISPR immune systems.","authors":"Wei Xiao, J L Weissman, Philip L F Johnson","doi":"10.1128/msystems.00568-24","DOIUrl":"10.1128/msystems.00568-24","url":null,"abstract":"<p><p>CRISPR-Cas is the only known adaptive immune system of prokaryotes. It is a powerful defense system against mobile genetic elements such as bacteriophages. While CRISPR-Cas systems can be found throughout the prokaryotic tree of life, they are distributed unevenly across taxa and environments. Since adaptive immunity is more useful in environments where pathogens persist or reoccur, the density and/or diversity of the host/pathogen community may drive the uneven distribution of CRISPR systems. We directly tested hypotheses connecting CRISPR incidence with prokaryotic density/diversity by analyzing 16S rRNA and metagenomic data from publicly available environmental sequencing projects. In terms of density, we found that CRISPR systems are significantly favored in lower abundance (less dense) taxa and disfavored in higher abundance taxa, at least in marine environments. When we extended this work to compare taxonomic diversity between samples, we found CRISPR system incidence strongly correlated with diversity in human oral environments. Together, these observations confirm that, at least in certain types of environments, the prokaryotic ecological context indeed plays a key role in selecting for CRISPR immunity.</p><p><strong>Importance: </strong>Microbes must constantly defend themselves against viral pathogens, and a large proportion of prokaryotes do so using the highly effective CRISPR-Cas adaptive immune system. However, many prokaryotes do not. We investigated the ecological factors behind this uneven distribution of CRISPR-Cas immune systems in natural microbial populations. We found strong patterns linking CRISPR-Cas systems to prokaryotic density within ocean environments and to prokaryotic diversity within human oral environments. Our study validates previous within-lab experimental results that suggested these factors might be important and confirms that local environment and ecological context interact to select for CRISPR immunity.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583526","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":"Stable, multigenerational transmission of the bean seed microbiome despite abiotic stress.","authors":"Abby Sulesky-Grieb, Marie Simonin, A Fina Bintarti, Brice Marolleau, Matthieu Barret, Ashley Shade","doi":"10.1128/msystems.00951-24","DOIUrl":"https://doi.org/10.1128/msystems.00951-24","url":null,"abstract":"<p><p>Microbiota that originate in the seed can have consequences for the education of the plant immune system, competitive exclusion of pathogens from the host tissue, and host access to critical nutrients. Our research objective was to investigate the consequences of the environmental conditions of the parent plant for bacterial seed microbiome assembly and transmission across plant generations. Using a fully factorial, three-generational experimental design, we investigated endophytic seed bacterial communities of common bean lines (<i>Phaseolus vulgaris</i> L.) grown in the growth chamber and exposed to either control conditions, drought, or excess nutrients at each generation. We applied 16S rRNA microbiome profiling to the seed endophytes and measured plant health outcomes. We discovered stable transmission of 22 bacterial members, regardless of the parental plant condition. This study shows the maintenance of bacterial members of the plant microbiome across generations, even under environmental stress. Overall, this work provides insights into the ability of plants to safeguard microbiome members, which has implications for crop microbiome management in the face of climate change.IMPORTANCESeed microbiomes initiate plant microbiome assembly and thus have critical implications for the healthy development and performance of crops. However, the consequences of environmental conditions of the parent plant for seed microbiome assembly and transmission are unknown, but this is critical information, given the intensifying stressors that crops face as the climate crisis accelerates. This study provides insights into the maintenance of plant microbiomes across generations, with implications for durable plant microbiome maintenance in agriculture on the changing planet.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546357","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":"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":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut and oral microbial compositional differences in women with breast cancer, women with ductal carcinoma <i>in situ</i>, and healthy women.","authors":"Emma McCune, Anukriti Sharma, Breanna Johnson, Tess O'Meara, Sarah Theiner, Maribel Campos, Diane Heditsian, Susie Brain, Jack A Gilbert, Laura Esserman, Michael J Campbell","doi":"10.1128/msystems.01237-24","DOIUrl":"10.1128/msystems.01237-24","url":null,"abstract":"<p><p>This study characterized and compared the fecal and oral microbiota from women with early-stage breast cancer (BC), women with ductal carcinoma <i>in situ</i> (DCIS), and healthy women. Fecal and oral samples were collected from newly diagnosed patients prior to any therapy and characterized using 16S rRNA sequencing. Measures of gut microbial alpha diversity were significantly lower in the BC vs healthy cohort. Beta diversity differed significantly between the BC or DCIS and healthy groups, and several differentially abundant taxa were identified. Clustering (non-negative matrix factorization) of the gut microbiota identified five bacterial guilds dominated by <i>Prevotella</i>, Enterobacteriaceae, <i>Akkermansia</i>, Clostridiales, or <i>Bacteroides</i>. The <i>Bacteroides</i> and Enterobacteriaceae guilds were significantly more abundant in the BC cohort compared to healthy controls, whereas the Clostridiales guild was more abundant in the healthy group. Finally, prediction of functional pathways identified 23 pathways that differed between the BC and healthy gut microbiota including lipopolysaccharide biosynthesis, glycan biosynthesis and metabolism, lipid metabolism, and sphingolipid metabolism. In contrast to the gut microbiomes, there were no significant differences in alpha or beta diversity in the oral microbiomes, and very few differentially abundant taxa were observed. Non-negative matrix factorization analysis of the oral microbiota samples identified seven guilds dominated by <i>Veillonella</i>, <i>Prevotella</i>, Gemellaceae, <i>Haemophilus</i>, <i>Neisseria</i>, <i>Propionibacterium</i>, and <i>Streptococcus</i>; however, none of these guilds were differentially associated with the different cohorts. Our results suggest that alterations in the gut microbiota may provide the basis for interventions targeting the gut microbiome to improve treatment outcomes and long-term prognosis.</p><p><strong>Importance: </strong>Emerging evidence suggests that the gut microbiota may play a role in breast cancer. Few studies have evaluated both the gut and oral microbiomes in women with breast cancer (BC), and none have characterized these microbiomes in women with ductal carcinoma <i>in situ</i> (DCIS). We surveyed the gut and oral microbiomes from women with BC or DCIS and healthy women and identified compositional and functional features of the gut microbiota that differed between these cohorts. In contrast, very few differential features were identified in the oral microbiota. Understanding the role of gut bacteria in BC and DCIS may open up new opportunities for the development of novel markers for early detection (or markers of susceptibility) as well as new strategies for prevention and/or treatment.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522474","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":"Metagenomic sequencing of CRISPRs as a new marker to aid in personal identification with low-biomass samples.","authors":"Kochi Toyomane, Yuri Kimura, Takashi Fukagawa, Takayuki Yamagishi, Ken Watanabe, Tomoko Akutsu, Ai Asahi, Satoshi Kubota, Kazumasa Sekiguchi","doi":"10.1128/msystems.01038-24","DOIUrl":"https://doi.org/10.1128/msystems.01038-24","url":null,"abstract":"<p><p>The high specificity of the human skin microbiome is expected to provide a new marker for personal identification. Metagenomic sequencing of clustered regularly interspaced short palindromic repeats (CRISPRs), which we call metaCRISPR typing, was shown to achieve personal identification accurately. However, the intra-individual variability observed in previous studies, which may be due to poor DNA yields from skin samples, has resulted in non-reproducible results. Furthermore, whether metaCRISPR typing can assist in the forensic human DNA analysis of low-biomass samples, from which the information obtained is insufficient, is unknown. In the present study, we sequenced serially diluted control streptococcal CRISPRs cloned into plasmids to determine the minimum copy number required to obtain reproducible results from metaCRISPR typing. We found that at least 10² copies of CRISPRs are necessary to obtain reproducible results. We then analyzed the skin swab samples using both metaCRISPR typing and human DNA typing. When the DNA extracted from the skin swabs was diluted, no information was obtained from six out of eight samples by human DNA typing. On the other hand, beta diversity indices of spacer sequences compared with reference samples were below 0.8 for three out of six samples, for which no information was obtained from human DNA analysis, indicating that the spacers observed in these samples were similar to those in the references. These results indicate that metaCRISPR typing may contribute to the identification of individuals from whom the samples were obtained, even in cases where human DNA yields are insufficient to perform human DNA analysis.IMPORTANCEPrevious studies have developed new personal identification methods utilizing personal differences in the skin microbiome. However, intra-individual diversity of skin microbiome may preclude the application of microbiome-based personal identification. Moreover, no study has compared microbiome-based personal identification and practical human DNA analysis. Here, we revealed that the results of metaCRISPR typing, a previously developed microbiome-based personal identification method, are stable if the copy number of the marker gene is sufficient. We then analyzed the skin swab samples using both metaCRISPR typing and human DNA analysis. Our results indicate that metaCRISPR typing may provide additional information for personal identification using low-biomass samples that cannot be used for conventional human DNA analysis.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The 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":"https://doi.org/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":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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":"https://doi.org/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":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new selective force driving metabolic gene clustering.","authors":"Marco Fondi, Francesco Pini, Christopher Riccardi, Pietro Gemo, Matteo Brilli","doi":"10.1128/msystems.00960-24","DOIUrl":"https://doi.org/10.1128/msystems.00960-24","url":null,"abstract":"<p><p>The evolution of operons has puzzled evolutionary biologists since their discovery, and many theories exist to explain their emergence, spreading, and evolutionary conservation. In this work, we suggest that DNA replication introduces a selective force for the clustering of functionally related genes on chromosomes, which we interpret as a preliminary and necessary step in operon formation. Our reasoning starts from the observation that DNA replication produces copy number variations of genomic regions, and we propose that such changes perturb metabolism. The formalization of this effect by exploiting concepts from metabolic control analysis suggests that the minimization of such perturbations during evolution could be achieved through the formation of gene clusters and operons. We support our theoretical derivations with simulations based on a realistic metabolic network, and we confirm that present-day genomes have a degree of compaction of functionally related genes, which is significantly correlated to the proposed perturbations introduced by replication. The formation of clusters of functionally related genes in microbial genomes has puzzled microbiologists since their first discovery. Here, we suggest that replication, and the copy number variations due to the replisome passage, might play a role in the process through a perturbation in metabolite homeostasis. We provide theoretical support to this hypothesis, and we found that both simulations and genomic analysis support our hypothesis.</p><p><strong>Importance: </strong>The formation of clusters of functionally related genes in microbial genomes has puzzled microbiologists since their discovery. Here, we suggest that replication, and the copy number variations due to the replisome passage, might play a role in the process through a perturbation in metabolite homeostasis. We provide theoretical support to this hypothesis, and we found that both simulations and genomic analysis support our hypothesis.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504402","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":"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":"https://doi.org/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":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}