mSystems最新文献

{"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":" ","pages":"e0123724"},"PeriodicalIF":5.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11575313/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional analysis of cyclic diguanylate-modulating proteins in <i>Vibrio fischeri</i>.","authors":"Ruth Y Isenberg, Chandler S Holschbach, Jing Gao, Mark J Mandel","doi":"10.1128/msystems.00956-24","DOIUrl":"10.1128/msystems.00956-24","url":null,"abstract":"<p><p>As bacterial symbionts transition from a motile free-living state to a sessile biofilm state, they must coordinate behavior changes suitable to each lifestyle. Cyclic diguanylate (c-di-GMP) is an intracellular signaling molecule that can regulate this transition, and it is synthesized by diguanylate cyclase (DGC) enzymes and degraded by phosphodiesterase (PDE) enzymes. Generally, c-di-GMP inhibits motility and promotes biofilm formation. While c-di-GMP and the enzymes that contribute to its metabolism have been well studied in pathogens, considerably less focus has been placed on c-di-GMP regulation in beneficial symbionts. <i>Vibrio fischeri</i> is the sole beneficial symbiont of the Hawaiian bobtail squid (<i>Euprymna scolopes</i>) light organ, and the bacterium requires both motility and biofilm formation to efficiently colonize. c-di-GMP regulates swimming motility and cellulose exopolysaccharide production in <i>V. fischeri</i>. The genome encodes 50 DGCs and PDEs, and while a few of these proteins have been characterized, the majority have not undergone comprehensive characterization. In this study, we use protein overexpression to systematically characterize the functional potential of all 50 <i>V</i>. <i>fischeri</i> proteins. All 28 predicted DGCs and 10 of the 14 predicted PDEs displayed at least one phenotype consistent with their predicted function, and a majority of each displayed multiple phenotypes. Finally, active site mutant analysis of proteins with the potential for both DGC and PDE activities revealed potential activities for these proteins. This work presents a systems-level functional analysis of a family of signaling proteins in a tractable animal symbiont and will inform future efforts to characterize the roles of individual proteins during lifestyle transitions.IMPORTANCECyclic diguanylate (c-di-GMP) is a critical second messenger that mediates bacterial behaviors, and <i>Vibrio fischeri</i> colonization of its Hawaiian bobtail squid host presents a tractable model in which to interrogate the role of c-di-GMP during animal colonization. This work provides systems-level characterization of the 50 proteins predicted to modulate c-di-GMP levels. By combining multiple assays, we generated a rich understanding of which proteins have the capacity to influence c-di-GMP levels and behaviors. Our functional approach yielded insights into how proteins with domains to both synthesize and degrade c-di-GMP may impact bacterial behaviors. Finally, we integrated published data to provide a broader picture of each of the 50 proteins analyzed. This study will inform future work to define specific pathways by which c-di-GMP regulates symbiotic behaviors and transitions.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0095624"},"PeriodicalIF":5.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11575326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470280","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":"Expanded genome and proteome reallocation in a novel, robust <i>Bacillus coagulans</i> strain capable of utilizing pentose and hexose sugars.","authors":"David Dooley, Seunghyun Ryu, Richard J Giannone, Jackson Edwards, Bruce S Dien, Patricia J Slininger, Cong T Trinh","doi":"10.1128/msystems.00952-24","DOIUrl":"10.1128/msystems.00952-24","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;i&gt;Bacillus coagulans,&lt;/i&gt; a Gram-positive thermophilic bacterium, is recognized for its probiotic properties and recent development as a microbial cell factory. Despite its importance for biotechnological applications, the current understanding of &lt;i&gt;B. coagulans&lt;/i&gt;' robustness is limited, especially for undomesticated strains. To fill this knowledge gap, we characterized the metabolic capability and performed functional genomics and systems analysis of a novel, robust strain, &lt;i&gt;B. coagulans&lt;/i&gt; B-768. Genome sequencing revealed that B-768 has the largest &lt;i&gt;B. coagulans&lt;/i&gt; genome known to date (3.94 Mbp), about 0.63 Mbp larger than the average genome of sequenced &lt;i&gt;B. coagulans&lt;/i&gt; strains, with expanded carbohydrate metabolism and mobilome. Functional genomics identified a well-equipped genetic portfolio for utilizing a wide range of C5 (xylose, arabinose), C6 (glucose, mannose, galactose), and C12 (cellobiose) sugars present in biomass hydrolysates, which was validated experimentally. For growth on individual xylose and glucose, the dominant sugars in biomass hydrolysates, B-768 exhibited distinct phenotypes and proteome profiles. Faster growth and glucose uptake rates resulted in lactate overflow metabolism, which makes &lt;i&gt;B. coagulans&lt;/i&gt; a lactate overproducer; however, slower growth and xylose uptake diminished overflow metabolism due to the high energy demand for sugar assimilation. Carbohydrate Transport and Metabolism (COG-G), Translation (COG-J), and Energy Conversion and Production (COG-C) made up 60%-65% of the measured proteomes but were allocated differently when growing on xylose and glucose. The trade-off in proteome reallocation, with high investment in COG-C over COG-G, explains the xylose growth phenotype with significant upregulation of xylose metabolism, pyruvate metabolism, and tricarboxylic acid (TCA) cycle. Strain B-768 tolerates and effectively utilizes inhibitory biomass hydrolysates containing mixed sugars and exhibits hierarchical sugar utilization with glucose as the preferential substrate.IMPORTANCEThe robustness of &lt;i&gt;B. coagulans&lt;/i&gt; makes it a valuable microorganism for biotechnology applications; yet, this phenotype is not well understood at the cellular level. Through phenotypic characterization and systems analysis, this study elucidates the functional genomics and robustness of a novel, undomesticated strain, &lt;i&gt;B. coagulans&lt;/i&gt; B-768, capable of utilizing inhibitory switchgrass biomass hydrolysates. The genome of B-768, enriched with carbohydrate metabolism genes, demonstrates high regulatory capacity. The coordination of proteome reallocation in Carbohydrate Transport and Metabolism (COG-G), Translation (COG-J), and Energy Conversion and Production (COG-C) is critical for effective cell growth, sugar utilization, and lactate production &lt;i&gt;via&lt;/i&gt; overflow metabolism. Overall, B-768 is a novel, robust, and promising &lt;i&gt;B. coagulans&lt;/i&gt; strain that can be harnessed as a microbial biomanufacturing p","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0095224"},"PeriodicalIF":5.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11575207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391906","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":"Protein aggregation is a consequence of the dormancy-inducing membrane toxin TisB in <i>Escherichia coli</i>.","authors":"Florian H Leinberger, Liam Cassidy, Daniel Edelmann, Nicole E Schmid, Markus Oberpaul, Patrick Blumenkamp, Sebastian Schmidt, Ana Natriashvili, Maximilian H Ulbrich, Andreas Tholey, Hans-Georg Koch, Bork A Berghoff","doi":"10.1128/msystems.01060-24","DOIUrl":"10.1128/msystems.01060-24","url":null,"abstract":"<p><p>Bacterial dormancy is a valuable strategy to survive stressful conditions. Toxins from chromosomal toxin-antitoxin systems have the potential to halt cell growth, induce dormancy, and eventually promote a stress-tolerant persister state. Due to their potential toxicity when overexpressed, sophisticated expression systems are needed when studying toxin genes. Here, we present a moderate expression system for toxin genes based on an artificial 5' untranslated region. We applied the system to induce expression of the toxin gene <i>tisB</i> from the chromosomal type I toxin-antitoxin system <i>tisB/istR-1</i> in <i>Escherichia coli</i>. TisB is a small hydrophobic protein that targets the inner membrane, resulting in depolarization and ATP depletion. We analyzed TisB-producing cells by RNA-sequencing and revealed several genes with a role in recovery from TisB-induced dormancy, including the chaperone genes <i>ibpAB</i> and <i>spy</i>. The importance of chaperone genes suggested that TisB-producing cells are prone to protein aggregation, which was validated by an <i>in vivo</i> fluorescent reporter system. We moved on to show that TisB is an essential factor for protein aggregation upon DNA damage mediated by the fluoroquinolone antibiotic ciprofloxacin in <i>E. coli</i> wild-type cells. The occurrence of protein aggregates correlates with an extended dormancy duration, which underscores their importance for the life cycle of TisB-dependent persister cells.</p><p><strong>Importance: </strong>Protein aggregates occur in all living cells due to misfolding of proteins. In bacteria, protein aggregation is associated with cellular inactivity, which is related to dormancy and tolerance to stressful conditions, including exposure to antibiotics. In <i>Escherichia coli</i>, the membrane toxin TisB is an important factor for dormancy and antibiotic tolerance upon DNA damage mediated by the fluoroquinolone antibiotic ciprofloxacin. Here, we show that TisB provokes protein aggregation, which, in turn, promotes an extended state of cellular dormancy. Our study suggests that protein aggregation is a consequence of membrane toxins with the potential to affect the duration of dormancy and the outcome of antibiotic therapy.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0106024"},"PeriodicalIF":5.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11575346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391907","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":"Coral high molecular weight carbohydrates support opportunistic microbes in bacterioplankton from an algae-dominated reef.","authors":"Bianca M Thobor, Andreas F Haas, Christian Wild, Craig E Nelson, Linda Wegley Kelly, Jan-Hendrik Hehemann, Milou G I Arts, Meine Boer, Hagen Buck-Wiese, Nguyen P Nguyen, Inga Hellige, Benjamin Mueller","doi":"10.1128/msystems.00832-24","DOIUrl":"10.1128/msystems.00832-24","url":null,"abstract":"<p><p>High molecular weight (HMW; >1 kDa) carbohydrates are a major component of dissolved organic matter (DOM) released by benthic primary producers. Despite shifts from coral to algae dominance on many reefs, little is known about the effects of exuded carbohydrates on bacterioplankton communities in reef waters. We compared the monosaccharide composition of HMW carbohydrates exuded by hard corals and brown macroalgae and investigated the response of the bacterioplankton community of an algae-dominated Caribbean reef to the respective HMW fractions. HMW coral exudates were compositionally distinct from the ambient, algae-dominated reef waters and similar to coral mucus (high in arabinose). They further selected for opportunistic bacterioplankton taxa commonly associated with coral stress (i.e., <i>Rhodobacteraceae</i>, <i>Phycisphaeraceae</i>, <i>Vibrionaceae</i>, and <i>Flavobacteriales</i>) and significantly increased the predicted energy-, amino acid-, and carbohydrate-metabolism by 28%, 44%, and 111%, respectively. In contrast, HMW carbohydrates exuded by algae were similar to those in algae tissue extracts and reef water (high in fucose) and did not significantly alter the composition and predicted metabolism of the bacterioplankton community. These results confirm earlier findings of coral exudates supporting efficient trophic transfer, while algae exudates may have stimulated microbial respiration instead of biomass production, thereby supporting the microbialization of reefs. In contrast to previous studies, HMW coral and not algal exudates selected for opportunistic microbes, suggesting that a shift in the prevalent DOM composition and not the exudate type (i.e., coral vs algae) <i>per se</i>, may induce the rise of opportunistic microbial taxa.</p><p><strong>Importance: </strong>Dissolved organic matter (DOM) released by benthic primary producers fuels coral reef food webs. Anthropogenic stressors cause shifts from coral to algae dominance on many reefs, and resulting alterations in the DOM pool can promote opportunistic microbes and potential coral pathogens in reef water. To better understand these DOM-induced effects on bacterioplankton communities, we compared the carbohydrate composition of coral- and macroalgae-DOM and analyzed the response of bacterioplankton from an algae-dominated reef to these DOM types. In line with the proposed microbialization of reefs, coral-DOM was efficiently utilized, promoting energy transfer to higher trophic levels, whereas macroalgae-DOM likely stimulated microbial respiration over biomass production. Contrary to earlier findings, coral- and not algal-DOM selected for opportunistic microbial taxa, indicating that a change in the prevalent DOM composition, and not DOM type, may promote the rise of opportunistic microbes. Presented results may also apply to other coastal marine ecosystems undergoing benthic community shifts.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0083224"},"PeriodicalIF":5.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11575353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470274","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":"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":"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":" ","pages":"e0103824"},"PeriodicalIF":5.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11575304/pdf/","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":"OA","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":"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":" ","pages":"e0096024"},"PeriodicalIF":5.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11629862/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolution and maintenance of a large multidrug-resistant plasmid in a <i>Salmonella enterica</i> Typhimurium host under differing antibiotic selection pressures.","authors":"Ming Cheng, Jing-Jing Dai, Jin-Fei Zhang, Yu-Ting Su, Si-Qi Guo, Ruan-Yang Sun, Dong Wang, Jian Sun, Xiao-Ping Liao, Sheng Chen, Liang-Xing Fang","doi":"10.1128/msystems.01197-24","DOIUrl":"10.1128/msystems.01197-24","url":null,"abstract":"&lt;p&gt;&lt;p&gt;The dissemination of antibiotic resistance genes (ARGs) through plasmids is a major mechanism for the development of bacterial antimicrobial resistance. The adaptation and evolution mechanisms of multidrug-resistant (MDR) plasmids with their hosts are not fully understood. Herein, we conducted experimental evolution of a 244 kb MDR plasmid (pJXP9) under various conditions including no antibiotics and mono- or combinational drug treatments of colistin (CS), cefotaxime (CTX), and ciprofloxacin (CIP). Our results showed that long-term with or without positive selections for pJXP9, spanning approximately 600 generations, led to modifications of the plasmid-encoded MDR and conjugative transfer regions. These modifications could mitigate the fitness cost of plasmid carriage and enhance plasmid maintenance. The extent of plasmid modifications and the evolution of plasmid-encoded antibiotic resistance depended on treatment type, particularly the drug class and duration of exposure. Interestingly, prolonged exposure to mono- and combinational drugs of CS and CIP resulted in a substantial loss of the plasmid-encoded MDR region and antibiotic resistance, comparable to the selection condition without antibiotic. By contrast, combinational treatment with CTX contributed to the maintenance of the MDR region over a long period of time. Furthermore, drug selection was able to maintain and even amplify the corresponding plasmid-encoded ARGs, with co-selection of ARGs in the adjacent regions. In addition, parallel mutations in chromosomal &lt;i&gt;arcA&lt;/i&gt; were also found to be associated with pJXP9 plasmid carriage among endpoint-evolved clones from diverse treatments. Meanwhile, &lt;i&gt;arcA&lt;/i&gt; deletion improved the persistence of pJXP9 plasmid without drugs. Overall, our findings indicated that plasmid-borne MDR region deletion and chromosomal &lt;i&gt;arcA&lt;/i&gt; inactivation mutation jointly contributed to co-adaptation and co-evolution between MDR IncHI2 plasmid and &lt;i&gt;Salmonella&lt;/i&gt; Typhimurium under different drug selection pressure.IMPORTANCEThe plasmid-mediated dissemination of antibiotic resistance genes has become a significant concern for human health, even though the carriage of multidrug-resistant (MDR) plasmids is frequently associated with fitness costs for the bacterial host. However, the mechanisms by which MDR plasmids and bacterial pairs evolve plasmid-mediated antibiotic resistance in the presence of antibiotic selections are not fully understood. Herein, we conducted an experimental evolution of a large multidrug-resistant plasmid in a &lt;i&gt;Salmonella enterica&lt;/i&gt; Typhimurium host under single and combinatorial drug selection pressures. Our results show the adaptive evolution of plasmid-encoded antibiotic resistance through alterations of the MDR region in the plasmid, in particular substantial loss of the MDR region, in response to different positive selections, especially mono- and combinational drugs of colistin and ciprofloxacin. In addition, strong pa","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0119724"},"PeriodicalIF":5.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11575406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated analysis of microbiota and gut microbial metabolites in blood for breast cancer.","authors":"Yu Peng, Jiale Gu, Fubin Liu, Peng Wang, Xixuan Wang, Changyu Si, Jianxiao Gong, Huijun Zhou, Ailing Qin, Fangfang Song","doi":"10.1128/msystems.00643-24","DOIUrl":"10.1128/msystems.00643-24","url":null,"abstract":"<p><p>Gut microbiota and associated metabolites have been linked to breast carcinogenesis. Evidences demonstrate blood microbiota primarily originates from the gut and may act as a biomarker for breast cancer. We aimed to characterize the microbiota-gut microbial metabolites cross-talk in blood and develop a composite diagnostic panel for breast cancer. We performed 16S rRNA gene sequencing and metabolomics profiling on blood samples from 107 breast cancer cases and 107 age-paired controls. We found that the alpha diversity of the blood microbiota was decreased in breast cancer compared to controls. There were significantly different profiles of microbiota and gut microbial metabolites in blood between these two groups, with nine bacterial genera and four gut microbial metabolites increased in patients, while thirty-nine bacterial genera and two gut microbial metabolites increased in controls. Some breast cancer-associated gut microbial metabolites were linked to differential blood microbiota, and a composite microbiota-metabolite diagnostic panel was further developed with an area under the curve of 0.963 for breast cancer. This study underscored the pivotal role of microbiota and gut microbial metabolites in blood and their interactions for breast carcinogenesis, as well as the potential of a composite diagnostic panel as a non-invasive biomarker for breast cancer.IMPORTANCEOur integrated analysis demonstrated altered profiles of microbiota and gut microbial metabolites in blood for breast cancer patients. The extensive correlation between microbiota and gut microbial metabolites in blood assisted the understanding of the pathogenesis of breast cancer. The good performance of a composite microbiota-gut microbial metabolites panel in blood suggested a non-invasive approach for breast cancer detection and a novel strategy for better diagnosis and prevention of breast cancer in the future.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0064324"},"PeriodicalIF":5.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11575300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470282","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":"Marine biofilms: cyanobacteria factories for the global oceans.","authors":"Cheng Zhong, Shun Yamanouchi, Yingdong Li, Jiawei Chen, Tong Wei, Ruojun Wang, Kun Zhou, Aifang Cheng, Weiduo Hao, Hongbin Liu, Kurt O Konhauser, Wataru Iwasaki, Pei-Yuan Qian","doi":"10.1128/msystems.00317-24","DOIUrl":"10.1128/msystems.00317-24","url":null,"abstract":"<p><p>Marine biofilms were newly revealed as a giant microbial diversity pool for global oceans. However, the cyanobacterial diversity in marine biofilms within the upper seawater column and its ecological and evolutionary implications remains undetermined. Here, we reconstructed a full picture of modern marine cyanobacteria habitats by re-analyzing 9.3 terabyte metagenomic data sets and 2,648 metagenome-assembled genomes (MAGs). The abundances of cyanobacteria lineages exclusively detected in marine biofilms were up to ninefold higher than those in seawater at similar sample size. Analyses revealed that cyanobacteria in marine biofilms are specialists with strong geographical and environmental constraints on their genome and functional adaption, which is in stark contrast to the generalistic features of seawater-derived cyanobacteria. Molecular dating suggests that the important diversifications in biofilm-forming cyanobacteria appear to coincide with the Great Oxidation Event (GOE), \"boring billion\" middle Proterozoic, and the Neoproterozoic Oxidation Event (NOE). These new insights suggest that marine biofilms are large and important cyanobacterial factories for the global oceans.</p><p><strong>Importance: </strong>Cyanobacteria, highly diverse microbial organisms, play a crucial role in Earth's oxygenation and biogeochemical cycling. However, their connection to these processes remains unclear, partly due to incomplete surveys of oceanic niches. Our study uncovered significant cyanobacterial diversity in marine biofilms, showing distinct niche differentiation compared to seawater counterparts. These patterns reflect three key stages of marine cyanobacterial diversification, coinciding with major geological events in the Earth's history.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0031724"},"PeriodicalIF":5.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11575276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470283","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}