microLife最新文献

{"title":"Local signaling enhances output specificity of bacterial c-di-GMP signaling networks.","authors":"Eike H Junkermeier,&nbsp;Regine Hengge","doi":"10.1093/femsml/uqad026","DOIUrl":"https://doi.org/10.1093/femsml/uqad026","url":null,"abstract":"<p><p>For many years the surprising multiplicity, signal input diversity, and output specificity of c-di-GMP signaling proteins has intrigued researchers studying bacterial second messengers. How can several signaling pathways act in parallel to produce specific outputs despite relying on the same diffusible second messenger maintained at a certain global cellular concentration? Such high specificity and flexibility arise from combining modes of local and global c-di-GMP signaling in complex signaling networks. Local c-di-GMP signaling can be experimentally shown by three criteria being met: (i) highly specific knockout phenotypes for particular c-di-GMP-related enzymes, (ii) actual cellular c-di-GMP levels that remain unchanged by such mutations and/or below the K_d's of the relevant c-di-GMP-binding effectors, and (iii) direct interactions between the signaling proteins involved. Here, we discuss the rationale behind these criteria and present well-studied examples of local c-di-GMP signaling in <i>Escherichia coli</i> and <i>Pseudomonas</i>. Relatively simple systems just colocalize a local source and/or a local sink for c-di-GMP, i.e. a diguanylate cyclase (DGC) and/or a specific phosphodiesterase (PDE), respectively, with a c-di-GMP-binding effector/target system. More complex systems also make use of regulatory protein interactions, e.g. when a \"trigger PDE\" responds to locally provided c-di-GMP, and thereby serves as a c-di-GMP-sensing effector that directly controls a target's activity, or when a c-di-GMP-binding effector recruits and directly activates its own \"private\" DGC. Finally, we provide an outlook into how cells can combine local and global signaling modes of c-di-GMP and possibly integrate those into other signaling nucleotides networks.</p>","PeriodicalId":74189,"journal":{"name":"microLife","volume":"4 ","pages":"uqad026"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/df/7c/uqad026.PMC10211494.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9546756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Control of light-dependent behaviour in cyanobacteria by the second messenger cyclic di-GMP.","authors":"Gen Enomoto,&nbsp;Thomas Wallner,&nbsp;Annegret Wilde","doi":"10.1093/femsml/uqad019","DOIUrl":"https://doi.org/10.1093/femsml/uqad019","url":null,"abstract":"<p><p>Nucleotide-derived signalling molecules control a wide range of cellular processes in all organisms. The bacteria-specific cyclic dinucleotide c-di-GMP plays a crucial role in regulating motility-to-sessility transitions, cell cycle progression, and virulence. Cyanobacteria are phototrophic prokaryotes that perform oxygenic photosynthesis and are widespread microorganisms that colonize almost all habitats on Earth. In contrast to photosynthetic processes that are well understood, the behavioural responses of cyanobacteria have rarely been studied in detail. Analyses of cyanobacterial genomes have revealed that they encode a large number of proteins that are potentially involved in the synthesis and degradation of c-di-GMP. Recent studies have demonstrated that c-di-GMP coordinates many different aspects of the cyanobacterial lifestyle, mostly in a light-dependent manner. In this review, we focus on the current knowledge of light-regulated c-di-GMP signalling systems in cyanobacteria. Specifically, we highlight the progress made in understanding the most prominent behavioural responses of the model cyanobacterial strains <i>Thermosynechococcus vulcanus</i> and <i>Synechocystis</i> sp. PCC 6803. We discuss why and how cyanobacteria extract crucial information from their light environment to regulate ecophysiologically important cellular responses. Finally, we emphasize the questions that remain to be addressed.</p>","PeriodicalId":74189,"journal":{"name":"microLife","volume":"4 ","pages":"uqad019"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f2/99/uqad019.PMC10124867.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10008578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The mysterious diadenosine tetraphosphate (AP4A).","authors":"Victor Zegarra,&nbsp;Christopher-Nils Mais,&nbsp;Johannes Freitag,&nbsp;Gert Bange","doi":"10.1093/femsml/uqad016","DOIUrl":"https://doi.org/10.1093/femsml/uqad016","url":null,"abstract":"<p><p>Dinucleoside polyphosphates, a class of nucleotides found amongst all the Trees of Life, have been gathering a lot of attention in the past decades due to their putative role as cellular alarmones. In particular, diadenosine tetraphosphate (AP4A) has been widely studied in bacteria facing various environmental challenges and has been proposed to be important for ensuring cellular survivability through harsh conditions. Here, we discuss the current understanding of AP4A synthesis and degradation, protein targets, their molecular structure where possible, and insights into the molecular mechanisms of AP4A action and its physiological consequences. Lastly, we will briefly touch on what is known with regards to AP4A beyond the bacterial kingdom, given its increasing appearance in the eukaryotic world. Altogether, the notion that AP4A is a conserved second messenger in organisms ranging from bacteria to humans and is able to signal and modulate cellular stress regulation seems promising.</p>","PeriodicalId":74189,"journal":{"name":"microLife","volume":"4 ","pages":"uqad016"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10148737/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9516280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advances and perspectives in nucleotide second messenger signaling in bacteria.","authors":"Regine Hengge,&nbsp;Mihaela Pruteanu,&nbsp;Jörg Stülke,&nbsp;Natalia Tschowri,&nbsp;Kürşad Turgay","doi":"10.1093/femsml/uqad015","DOIUrl":"https://doi.org/10.1093/femsml/uqad015","url":null,"abstract":"<p><p>Nucleotide second messengers act as intracellular 'secondary' signals that represent environmental or cellular cues, i.e. the 'primary' signals. As such, they are linking sensory input with regulatory output in all living cells. The amazing physiological versatility, the mechanistic diversity of second messenger synthesis, degradation, and action as well as the high level of integration of second messenger pathways and networks in prokaryotes has only recently become apparent. In these networks, specific second messengers play conserved general roles. Thus, (p)ppGpp coordinates growth and survival in response to nutrient availability and various stresses, while c-di-GMP is <i>the</i> nucleotide signaling molecule to orchestrate bacterial adhesion and multicellularity. c-di-AMP links osmotic balance and metabolism and that it does so even in Archaea may suggest a very early evolutionary origin of second messenger signaling. Many of the enzymes that make or break second messengers show complex sensory domain architectures, which allow multisignal integration. The multiplicity of c-di-GMP-related enzymes in many species has led to the discovery that bacterial cells are even able to use the same freely diffusible second messenger in local signaling pathways that can act in parallel without cross-talking. On the other hand, signaling pathways operating with different nucleotides can intersect in elaborate signaling networks. Apart from the small number of common signaling nucleotides that bacteria use for controlling their cellular \"business,\" diverse nucleotides were recently found to play very specific roles in phage defense. Furthermore, these systems represent the phylogenetic ancestors of cyclic nucleotide-activated immune signaling in eukaryotes.</p>","PeriodicalId":74189,"journal":{"name":"microLife","volume":"4 ","pages":"uqad015"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/66/33/uqad015.PMC10118264.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9522018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small regulatory RNAs in <i>Vibrio cholerae</i>.","authors":"Rabea Ghandour,&nbsp;Kai Papenfort","doi":"10.1093/femsml/uqad030","DOIUrl":"https://doi.org/10.1093/femsml/uqad030","url":null,"abstract":"<p><p><i>Vibrio cholerae</i> is a major human pathogen causing the diarrheal disease, cholera. Regulation of virulence in <i>V. cholerae</i> is a multifaceted process involving gene expression changes at the transcriptional and post-transcriptional level. Whereas various transcription factors have been reported to modulate virulence in <i>V. cholerae</i>, small regulatory RNAs (sRNAs) have now been established to also participate in virulence control and the regulation of virulence-associated processes, such as biofilm formation, quorum sensing, stress response, and metabolism. In most cases, these sRNAs act by base-pairing with multiple target transcripts and this process typically requires the aid of an RNA-binding protein, such as the widely conserved Hfq protein. This review article summarizes the functional roles of sRNAs in <i>V. cholerae</i>, their underlying mechanisms of gene expression control, and how sRNAs partner with transcription factors to modulate complex regulatory programs. In addition, we will discuss regulatory principles discovered in <i>V. cholerae</i> that not only apply to other <i>Vibrio</i> species, but further extend into the large field of RNA-mediated gene expression control in bacteria.</p>","PeriodicalId":74189,"journal":{"name":"microLife","volume":"4 ","pages":"uqad030"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/77/db/uqad030.PMC10335731.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9872402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"(p)ppGpp and moonlighting RNases influence the first step of lipopolysaccharide biosynthesis in <i>Escherichia coli</i>.","authors":"Simon Brückner,&nbsp;Fabian Müller,&nbsp;Laura Schadowski,&nbsp;Tyll Kalle,&nbsp;Sophia Weber,&nbsp;Emily C Marino,&nbsp;Blanka Kutscher,&nbsp;Anna-Maria Möller,&nbsp;Sabine Adler,&nbsp;Dominik Begerow,&nbsp;Wieland Steinchen,&nbsp;Gert Bange,&nbsp;Franz Narberhaus","doi":"10.1093/femsml/uqad031","DOIUrl":"https://doi.org/10.1093/femsml/uqad031","url":null,"abstract":"<p><p>The outer membrane (OM) protects Gram-negative bacteria from harsh environmental conditions and provides intrinsic resistance to many antimicrobial compounds. The asymmetric OM is characterized by phospholipids in the inner leaflet and lipopolysaccharides (LPS) in the outer leaflet. Previous reports suggested an involvement of the signaling nucleotide ppGpp in cell envelope homeostasis in <i>Escherichia coli</i>. Here, we investigated the effect of ppGpp on OM biosynthesis. We found that ppGpp inhibits the activity of LpxA, the first enzyme of LPS biosynthesis, in a fluorometric <i>in vitro</i> assay. Moreover, overproduction of LpxA resulted in elongated cells and shedding of outer membrane vesicles (OMVs) with altered LPS content. These effects were markedly stronger in a ppGpp-deficient background. We further show that RnhB, an RNase H isoenzyme, binds ppGpp, interacts with LpxA, and modulates its activity. Overall, our study uncovered new regulatory players in the early steps of LPS biosynthesis, an essential process with many implications in the physiology and susceptibility to antibiotics of Gram-negative commensals and pathogens.</p>","PeriodicalId":74189,"journal":{"name":"microLife","volume":"4 ","pages":"uqad031"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ba/10/uqad031.PMC10326835.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9866291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cyclic di-AMP, a multifaceted regulator of central metabolism and osmolyte homeostasis in <i>Listeria monocytogenes</i>.","authors":"Inge Schwedt,&nbsp;Mengyi Wang,&nbsp;Johannes Gibhardt,&nbsp;Fabian M Commichau","doi":"10.1093/femsml/uqad005","DOIUrl":"https://doi.org/10.1093/femsml/uqad005","url":null,"abstract":"<p><p>Cyclic di-AMP is an emerging second messenger that is synthesized by many archaea and bacteria, including the Gram-positive pathogenic bacterium <i>Listeria monocytogenes. Listeria monocytogenes</i> played a crucial role in elucidating the essential function of c-di-AMP, thereby becoming a model system for studying c-di-AMP metabolism and the influence of the nucleotide on cell physiology. c-di-AMP is synthesized by a diadenylate cyclase and degraded by two phosphodiesterases. To date, eight c-di-AMP receptor proteins have been identified in <i>L. monocytogenes</i>, including one that indirectly controls the uptake of osmotically active peptides and thus the cellular turgor. The functions of two c-di-AMP-receptor proteins still need to be elucidated. Here, we provide an overview of c-di-AMP signalling in <i>L. monocytogenes</i> and highlight the main differences compared to the other established model systems in which c-di-AMP metabolism is investigated. Moreover, we discuss the most important questions that need to be answered to fully understand the role of c-di-AMP in osmoregulation and in the control of central metabolism.</p>","PeriodicalId":74189,"journal":{"name":"microLife","volume":"4 ","pages":"uqad005"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/47/d0/uqad005.PMC10117814.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9516276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The New Microbiology: an international lecture course on the island of Spetses.","authors":"Pascale Cossart,&nbsp;Roberto Kolter,&nbsp;Bruno Lemaitre,&nbsp;Athanasios Typas","doi":"10.1093/femsml/uqac026","DOIUrl":"https://doi.org/10.1093/femsml/uqac026","url":null,"abstract":"<p><p>In September 2022, an international summer course entitled 'The new microbiology' took place in Greece, on the island of Spetses. The organizers aimed to highlight the spectacular advances and the renaissance occurring in Microbiology, driven by developments in genomics, proteomics, imaging techniques, and bioinformatics. Combinations of these advances allow for single cell analyses, rapid and relatively inexpensive metagenomic and transcriptomic data analyses and comparisons, visualization of previously unsuspected mechanisms, and large-scale studies. A 'New Microbiology' is emerging which allows studies that address the critical roles of microbes in health and disease, in humans, animals, and the environment. The concept of one health is now transforming microbiology. The goal of the course was to discuss all these topics with members of the new generation of microbiologists all of whom were highly motivated and fully receptive.</p>","PeriodicalId":74189,"journal":{"name":"microLife","volume":"4 ","pages":"uqac026"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10212125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9545272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dear <i>Listeria</i>, what is your preferred niche?","authors":"Sarah Wettstadt","doi":"10.1093/femsml/uqad004","DOIUrl":"https://doi.org/10.1093/femsml/uqad004","url":null,"abstract":"Seeing Pascale Cossart in one of her many science outreach videos online, one can usually recognize two major features: a lot of scientific expertise and a big smile. Both stem from her experience of being a microbiologist and her passion for the field. After her PhD in chemistry at the University of Paris, Pascale came across the microbial world by studying protein–DNA interactions. She learned about microbial physiology and started to study how microbes interact with their hosts. She then got more and more fascinated by microbes and the fact that they ‘are not only everywhere, but they are absolutely critical for the equilibrium of the human body, animals, plants, insects and the environment’. From early on, Pascale decided to focus on the Gram-positive pathogen Listeria monocytogenes, which can live silently in the gastro-intestinal tract of some healthy humans. However, in immuno-compromised people, newborns, elderly, or pregnant women, it can lead to severe infections and meningitis, encephalitis, or even miscarriage. Pascale was the first to sequence the hlyA gene, which encodes listeriolysin O—a major virulence factor— in Listeria. Together with her team, Pascale then discovered internalin, the protein that allows Listeria to enter mammalian cells, as well as its receptor on mammalian cells, the protein E-cadherin. She then became interested in how Listeria would enter host cells, and she identified many important key molecules whose role in bacterial cell entry had never been suspected. Her work on Listeria specificity for human cells versus murine was remarkable and led to the generation of a transgenic animal model for human listeriosis. As an early-stage Professor at the Institut Pasteur in Paris, Pascale made a discovery that ‘triggered a whole tsunami in the field’. She discovered the mechanisms of how L. monocytogenes uses the actin of a host to move and spread across tissue. Once inside the cytosol of the host cell, the bacterial surface protein ActA nucleates and polymerizes actin and recruits other proteins to these actin filaments (Kocks et al. 1992). Through this polymerization process, ActA triggers the formation of long actin tails and ultimately of bacteria-containing membrane protrusions. These help L. monocytogenes contact and enter neighbouring cells without ever leaving the host cytosol (Lecuit et al. 2001). Thanks to growing techniques like fluorescence microscopy, Pascale and her team managed to visualize these microbe-induced processes and establish herself in the field of infection microbiology.","PeriodicalId":74189,"journal":{"name":"microLife","volume":"4 ","pages":"uqad004"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1d/26/uqad004.PMC10117850.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9516278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From an Hsp90 - binding protein to a peptide drug.","authors":"Aparna Viswanathan Ammanath,&nbsp;Anders Jarneborn,&nbsp;Minh-Thu Nguyen,&nbsp;Laura Wessling,&nbsp;Paula Tribelli,&nbsp;Mulugeta Nega,&nbsp;Christian Beck,&nbsp;Arif Luqman,&nbsp;Khaled A Selim,&nbsp;Hubert Kalbacher,&nbsp;Boris Macek,&nbsp;Sandra Beer Hammer,&nbsp;Tao Jin,&nbsp;Friedrich Götz","doi":"10.1093/femsml/uqac023","DOIUrl":"https://doi.org/10.1093/femsml/uqac023","url":null,"abstract":"<p><p>The Lpl proteins represent a class of lipoproteins that was first described in the opportunistic bacterial pathogen <i>Staphylococcus aureus</i>, where they contribute to pathogenicity by enhancing F-actin levels of host epithelial cells and thereby increasing <i>S. aureus</i> internalization. The model Lpl protein, Lpl1 was shown to interact with the human heat shock proteins Hsp90α and Hsp90ß, suggesting that this interaction may trigger all observed activities. Here we synthesized Lpl1-derived peptides of different lengths and identified two overlapping peptides, namely, L13 and L15, which interacted with Hsp90α. Unlike Lpl1, the two peptides not only decreased F-actin levels and <i>S. aureus</i> internalization in epithelial cells but they also decreased phagocytosis by human CD14⁺ monocytes. The well-known Hsp90 inhibitor, geldanamycin, showed a similar effect. The peptides not only interacted directly with Hsp90α, but also with the mother protein Lpl1. While L15 and L13 significantly decreased lethality of <i>S. aureus</i> bacteremia in an insect model, geldanamycin did not. In a mouse bacteremia model L15 was found to significantly decreased weight loss and lethality. Although the molecular bases of the L15 effect is still elusive, <i>in vitro</i> data indicate that simultaneous treatment of host immune cells with L15 or L13 and <i>S. aureus</i> significantly increase IL-6 production. L15 and L13 represent not antibiotics but they cause a significant reduction in virulence of multidrug-resistant <i>S. aureus</i> strains in <i>in vivo</i> models. In this capacity, they can be an important drug alone or additive with other agents.</p>","PeriodicalId":74189,"journal":{"name":"microLife","volume":"4 ","pages":"uqac023"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10117725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9518991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}