Molecular Microbiology最新文献

{"title":"Multiple Effects of L-Leucine in Escherichia coli Lead to L-Leucine-Sensitive Growth in the Absence of Unphosphorylated PtsN","authors":"Neeraj Kumar, Abhijit A. Sardesai","doi":"10.1111/mmi.15317","DOIUrl":"https://doi.org/10.1111/mmi.15317","url":null,"abstract":"In <i>E. coli</i> K-12, the absence of unphosphorylated PtsN (unphospho-PtsN) has been proposed to cause an L-leucine-sensitive growth phenotype (Leu^S) by hyperactivated K⁺ uptake mediated impairment of the expression of the <i>ilvBN</i> operon, encoding subunits of the L-valine (Val)-sensitive acetohydroxyacid synthase I (AHAS I) that renders residual AHAS activity susceptible to inhibition by Leu and K⁺. This leads to AHAS insufficiency and a requirement for L-isoleucine (Ile). Herein, we provide an alternate mechanism for the Leu^S of the ∆<i>ptsN</i> mutant. Genetic and physiological studies with suppressors of the Leu^S indicate that impaired expression of the <i>ilvBN</i> operon jointly caused by the absence of unphospho-PtsN and the presence of Leu coupled to Leu-mediated repression of expression of AHAS III leads to AHAS insufficiency rendering residual AHAS activity susceptible to chronic Val stress that may be generated by exogenous Leu. Hyperactivated K⁺ uptake and an elevated α-ketobutyrate level mediate elevation of <i>ilvBN</i> expression and alleviate the Leu^S. The requirement of unphospho-PtsN as a positive regulator of <i>ilvBN</i> expression may buffer Ile biosynthesis against Leu-mediated AHAS insufficiency and protect AHAS I function from chronic endogenous Val generated by Leu and could be realized in certain environments that impair AHAS function.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"46 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231820","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 Impact of YabG Mutations on Clostridioides difficile Spore Germination and Processing of Spore Substrates","authors":"Morgan S. Osborne, Joshua N. Brehm, Carmen Olivença, Alicia M. Cochran, Mónica Serrano, Adriano O. Henriques, Joseph A. Sorg","doi":"10.1111/mmi.15316","DOIUrl":"https://doi.org/10.1111/mmi.15316","url":null,"abstract":"YabG is a sporulation‐specific protease that is conserved among sporulating bacteria. <jats:italic>Clostridioides difficile</jats:italic> YabG processes the cortex destined proteins preproSleC into proSleC and CspBA to CspB and CspA. YabG also affects synthesis of spore coat/exosporium proteins CotA and CdeM. In prior work that identified CspA as the co‐germinant receptor, mutations in <jats:italic>yabG</jats:italic> were found which altered the co‐germinants required to initiate spore germination. To understand how these mutations in the <jats:italic>yabG</jats:italic> locus contribute to <jats:italic>C</jats:italic>. <jats:italic>difficile</jats:italic> spore germination, we introduced these mutations into an isogenic background. Spores derived from <jats:italic>C</jats:italic>. <jats:italic>difficile yabG</jats:italic><jats:sub>C207A</jats:sub> (a catalytically inactive allele), <jats:italic>C</jats:italic>. <jats:italic>difficile yabG</jats:italic><jats:sub>A46D</jats:sub>, <jats:italic>C</jats:italic>. <jats:italic>difficile yabG</jats:italic><jats:sub>G37E</jats:sub>, and <jats:italic>C</jats:italic>. <jats:italic>difficile yabG</jats:italic><jats:sub>P153L</jats:sub> strains germinated in response to taurocholic acid alone. Recombinantly expressed and purified preproSleC incubated with <jats:italic>E</jats:italic>. <jats:italic>coli</jats:italic> lysate expressing wild type YabG resulted in the removal of the presequence from preproSleC. Interestingly, only YabG<jats:sub>A46D</jats:sub> showed any activity toward purified preproSleC. Mutation of the YabG processing site in preproSleC (R119A) led to YabG shifting its processing to R115 or R112. Finally, changes in <jats:italic>yabG</jats:italic> expression under the mutant promoters were analyzed using a SNAP‐tag and revealed expression differences at early and late stages of sporulation. Overall, our results support and expand upon the hypothesis that YabG is important for germination and spore assembly and, upon mutation of the processing site, can shift where it cleaves substrates.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"9 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170937","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":"Molecular Microbiology of Microbiomes","authors":"Pierre Santucci","doi":"10.1111/mmi.15308","DOIUrl":"https://doi.org/10.1111/mmi.15308","url":null,"abstract":"","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"97 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170934","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":"Lactobacillus gasseri and Gardnerella vaginalis produce extracellular vesicles that contribute to the function of the vaginal microbiome and modulate host-Trichomonas vaginalis interactions.","authors":"Anastasiia Artuyants, Jiwon Hong, Priscila Dauros-Singorenko, Anthony Phillips, Augusto Simoes-Barbosa","doi":"10.1111/mmi.15130","DOIUrl":"10.1111/mmi.15130","url":null,"abstract":"<p><p>Trichomonas vaginalis is an extracellular protozoan parasite of the human urogenital tract, responsible for a prevalent sexually transmitted infection. Trichomoniasis is accompanied by a dysbiotic microbiome that is characterised by the depletion of host-protective commensals such as Lactobacillus gasseri, and the flourishing of a bacterial consortium that is comparable to the one seen for bacterial vaginosis, including the founder species Gardnerella vaginalis. These two vaginal bacteria are known to have opposite effects on T. vaginalis pathogenicity. Studies on extracellular vesicles (EVs) have been focused on the direction of a microbial producer (commensal or pathogen) to a host recipient, and largely in the context of the gut microbiome. Here, taking advantage of the simplicity of the human cervicovaginal microbiome, we determined the molecular cargo of EVs produced by L. gasseri and G. vaginalis and examined how these vesicles modulate the interaction of T. vaginalis and host cells. We show that these EVs carry a specific cargo of proteins, which functions can be attributed to the opposite roles that these bacteria play in the vaginal biome. Furthermore, these bacterial EVs are delivered to host and protozoan cells, modulating host-pathogen interactions in a way that mimics the opposite effects that these bacteria have on T. vaginalis pathogenicity. This is the first study to describe side-by-side the protein composition of EVs produced by two bacteria belonging to the opposite spectrum of a microbiome and to demonstrate that these vesicles modulate the pathogenicity of a protozoan parasite. Such as in trichomoniasis, infections and dysbiosis co-occur frequently resulting in significant co-morbidities. Therefore, studies like this provide the knowledge for the development of antimicrobial therapies that aim to clear the infection while restoring a healthy microbiome.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":" ","pages":"357-371"},"PeriodicalIF":2.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9860987","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":"Simvastatin induces human gut bacterial cell surface genes.","authors":"Veronica Escalante, Renuka R Nayak, Cecilia Noecker, Joel Babdor, Matthew Spitzer, Adam M Deutschbauer, Peter J Turnbaugh","doi":"10.1111/mmi.15151","DOIUrl":"10.1111/mmi.15151","url":null,"abstract":"<p><p>Drugs intended to target mammalian cells can have broad off-target effects on the human gut microbiota with potential downstream consequences for drug efficacy and side effect profiles. Yet, despite a rich literature on antibiotic resistance, we still know very little about the mechanisms through which commensal bacteria evade non-antibiotic drugs. Here, we focus on statins, one of the most prescribed drug types in the world and an essential tool in the prevention and treatment of high circulating cholesterol levels. Prior work in humans, mice, and cell culture support an off-target effect of statins on human gut bacteria; however, the genetic determinants of statin sensitivity remain unknown. We confirmed that simvastatin inhibits the growth of diverse human gut bacterial strains grown in communities and in pure cultures. Drug sensitivity varied between phyla and was dose-dependent. We selected two representative simvastatin-sensitive species for more in-depth analysis: Eggerthella lenta (phylum: Actinobacteriota) and Bacteroides thetaiotaomicron (phylum: Bacteroidota). Transcriptomics revealed that both bacterial species upregulate genes in response to simvastatin that alter the cell membrane, including fatty acid biogenesis (E. lenta) and drug efflux systems (B. thetaiotaomicron). Transposon mutagenesis identified a key efflux system in B. thetaiotaomicron that enables growth in the presence of statins. Taken together, these results emphasize the importance of the bacterial cell membrane in countering the off-target effects of host-targeted drugs. Continued mechanistic dissection of the various mechanisms through which the human gut microbiota evades drugs will be essential to understand and predict the effects of drug administration in human cohorts and the potential downstream consequences for health and disease.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":" ","pages":"372-386"},"PeriodicalIF":2.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10940213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10234832","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":"Space, the final frontier: The spatial component of phytoplankton-bacterial interactions.","authors":"Clara Martínez-Pérez, Sophie T Zweifel, Roberto Pioli, Roman Stocker","doi":"10.1111/mmi.15293","DOIUrl":"10.1111/mmi.15293","url":null,"abstract":"<p><p>Microscale interactions between marine phytoplankton and bacteria shape the microenvironment of individual cells, impacting their physiology and ultimately influencing global-scale biogeochemical processes like carbon and nutrient cycling. In dilute environments such as the ocean water column, metabolic exchange between microorganisms likely requires close proximity between partners. However, the biological strategies to achieve this physical proximity remain an understudied aspect of phytoplankton-bacterial associations. Understanding the mechanisms by which these microorganisms establish and sustain spatial relationships and the extent to which spatial proximity is necessary for interactions to occur, is critical to learning how spatial associations influence the ecology of phytoplankton and bacterial communities. Here, we provide an overview of current knowledge on the role of space in shaping interactions among ocean microorganisms, encompassing behavioural and metabolic evidence. We propose that characterising phytoplankton-bacterial interactions from a spatial perspective can contribute to a mechanistic understanding of the establishment and maintenance of these associations and, consequently, an enhanced ability to predict the impact of microscale processes on ecosystem-wide phenomena.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":" ","pages":"331-346"},"PeriodicalIF":2.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141545048","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":"Neuroactive metabolites modulated by the gut microbiota in honey bees.","authors":"Amélie Cabirol, Silvia Moriano-Gutierrez, Philipp Engel","doi":"10.1111/mmi.15167","DOIUrl":"10.1111/mmi.15167","url":null,"abstract":"<p><p>Honey bees have emerged as a new model to study the gut-brain axis, as they exhibit complex social behaviors and cognitive abilities, while experiments with gnotobiotic bees have revealed that their gut microbiota alters both brain and behavioral phenotypes. Furthermore, while honey bee brain functions supporting a broad range of behaviors have been intensively studied for over 50 years, the gut microbiota of bees has been experimentally characterized only recently. Here, we combined six published datasets from metabolomic analyses to provide an overview of the neuroactive metabolites whose abundance in the gut, hemolymph and brain varies in presence of the gut microbiota. Such metabolites may either be produced by gut bacteria, released from the pollen grains during their decomposition by bacteria, or produced by other organs in response to different bacterial products. We describe the current state of knowledge regarding the impact of such metabolites on brain function and behavior and provide further hypotheses to explore in this emerging field of research.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":" ","pages":"284-293"},"PeriodicalIF":2.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10279438","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":"From vacant to vivid: The nutritional landscape drives infant gut microbiota establishment.","authors":"Reut Melki, Yael Litvak","doi":"10.1111/mmi.15296","DOIUrl":"10.1111/mmi.15296","url":null,"abstract":"<p><p>From the moment of birth, the newborn gastrointestinal tract is infiltrated by various bacteria originating from both maternal and environmental sources. These colonizing bacteria form a complex microbiota community that undergoes continuous changes until adulthood and plays an important role in infant health. The maturation of the infant gut microbiota is driven by many factors and follows a distinct patterned trajectory, with specific bacterial taxa establish in the intestine in accordance with developmental milestones as the infant grows. In this review, we highlight how elements such as diet and host physiology select for specific microbial functions and shape the composition of the bacterial community in the large intestine.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":" ","pages":"347-356"},"PeriodicalIF":2.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752174","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":"Pilot study on nasal microbiota dynamics and MRSA carriage of a pig cohort housed on straw bedding.","authors":"Natalie Effelsberg, Iris Kobusch, Hannah Schollenbruch, Sabrina Linnemann, Corinna Bang, Andre Franke, Robin Köck, Marc Boelhauve, Alexander Mellmann","doi":"10.1111/mmi.15136","DOIUrl":"10.1111/mmi.15136","url":null,"abstract":"<p><p>Methicillin-resistant Staphylococcus aureus (MRSA) can be transmitted between pigs and humans on farms. Hence, the reduction of MRSA carriage in pigs could decrease the risk of zoonotic transmission. Recently, straw bedding has been found to significantly reduce MRSA carriage in pigs. The mechanisms behind this effect remain unclear but changes in the nasal microbiome may play a role. In this exploratory study, the nasal microbiota of pigs kept on straw was examined using V1/V2 16S rRNA gene sequencing. Nasal swabs were collected from 13 pigs at six different time points during the course of a full fattening cycle resulting in 74 porcine samples. In addition, straw samples were collected at each time point. Eleven out of 13 pigs were MRSA positive at housing-in. We found a strong temporal pattern in the microbial communities. Both microbial diversity and abundance of Staphylococcus species peaked in week 5 after introduction to the straw stable decreased in week 10, when all pigs turned MRSA-negative, and increased again toward the end of the fattening period. These findings show that the introduction of pigs into a new environment has a huge impact on their nasal microbiota, which might lead to unfavorable conditions for MRSA. Moreover, other Staphylococcus species may play a role in eliminating MRSA carriage. We designed a follow-up study including two different husbandry systems to further assess these effects.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":" ","pages":"403-412"},"PeriodicalIF":2.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10286894","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":"Unlocking the potential of microbiome editing: A review of conjugation-based delivery.","authors":"Pedro Dorado-Morales, Morgan Lambérioux, Didier Mazel","doi":"10.1111/mmi.15147","DOIUrl":"10.1111/mmi.15147","url":null,"abstract":"<p><p>In recent decades, there has been a rapid increase in the prevalence of multidrug-resistant pathogens, posing a challenge to modern antibiotic-based medicine. This has highlighted the need for novel treatments that can specifically affect the target microorganism without disturbing other co-inhabiting species, thus preventing the development of dysbiosis in treated patients. Moreover, there is a pressing demand for tools to effectively manipulate complex microbial populations. One of the approaches suggested to address both issues was to use conjugation as a tool to modify the microbiome by either editing the genome of specific bacterial species and/or the removal of certain taxonomic groups. Conjugation involves the transfer of DNA from one bacterium to another, which opens up the possibility of introducing, modifying or deleting specific genes in the recipient. In response to this proposal, there has been a significant increase in the number of studies using this method for gene delivery in bacterial populations. This MicroReview aims to provide a detailed overview on the use of conjugation for microbiome engineering, and at the same time, to initiate a discussion on the potential, limitations and possible future directions of this approach.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":" ","pages":"273-283"},"PeriodicalIF":2.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10137854","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}