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Computer-aided design of a cyclic di-AMP synthesizing enzyme CdaA inhibitor. 环二amp合成酶CdaA抑制剂的计算机辅助设计。
microLife Pub Date : 2023-01-01 DOI: 10.1093/femsml/uqad021
Piotr Neumann, Patrick Kloskowski, Ralf Ficner
{"title":"Computer-aided design of a cyclic di-AMP synthesizing enzyme CdaA inhibitor.","authors":"Piotr Neumann,&nbsp;Patrick Kloskowski,&nbsp;Ralf Ficner","doi":"10.1093/femsml/uqad021","DOIUrl":"https://doi.org/10.1093/femsml/uqad021","url":null,"abstract":"<p><p>Cyclic di-AMP (c-di-AMP) is an essential secondary messenger regulating cell wall homeostasis and myriads of physiological processes in several Gram-positive and mycobacteria, including human pathogens. Hence, c-di-AMP synthesizing enzymes (DACs) have become a promising antibacterial drug target. To overcome a scarcity of small molecule inhibitors of c-di-AMP synthesizing enzyme CdaA, a computer-aided design of a new compound that should block the enzyme has been performed. This has led to the identification of a molecule comprising two thiazole rings and showing inhibitory potential based on ITC measurements. Thiazole scaffold is a good pharmacophore nucleus known due to its various pharmaceutical applications. It is contained in more than 18 FDA-approved drugs as well as in dozens of experimental drugs. Hence, the designed inhibitor can serve as a potent lead compound for further development of inhibitor against CdaA.</p>","PeriodicalId":74189,"journal":{"name":"microLife","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10167629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9516281","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}
引用次数: 2
Ancestral reconstruction of the MotA stator subunit reveals that conserved residues far from the pore are required to drive flagellar motility. 对MotA定子亚基的祖先重建表明,远离孔的保守残基需要驱动鞭毛运动。
microLife Pub Date : 2023-01-01 DOI: 10.1093/femsml/uqad011
Md Imtiazul Islam, Pietro Ridone, Angela Lin, Katharine A Michie, Nicholas J Matzke, Georg Hochberg, Matthew A B Baker
{"title":"Ancestral reconstruction of the MotA stator subunit reveals that conserved residues far from the pore are required to drive flagellar motility.","authors":"Md Imtiazul Islam,&nbsp;Pietro Ridone,&nbsp;Angela Lin,&nbsp;Katharine A Michie,&nbsp;Nicholas J Matzke,&nbsp;Georg Hochberg,&nbsp;Matthew A B Baker","doi":"10.1093/femsml/uqad011","DOIUrl":"https://doi.org/10.1093/femsml/uqad011","url":null,"abstract":"<p><p>The bacterial flagellar motor (BFM) is a rotary nanomachine powered by the translocation of ions across the inner membrane through the stator complex. The stator complex consists of two membrane proteins: MotA and MotB (in H<sup>+</sup>-powered motors), or PomA and PomB (in Na<sup>+</sup>-powered motors). In this study, we used ancestral sequence reconstruction (ASR) to probe which residues of MotA correlate with function and may have been conserved to preserve motor function. We reconstructed 10 ancestral sequences of MotA and found four of them were motile in combination with contemporary <i>Escherichia coli</i> MotB and in combination with our previously published functional ancestral MotBs. Sequence comparison between wild-type (WT) <i>E. coli</i> MotA and MotA-ASRs revealed 30 critical residues across multiple domains of MotA that were conserved among all motile stator units. These conserved residues included pore-facing, cytoplasm-facing, and MotA-MotA intermolecular facing sites. Overall, this work demonstrates the role of ASR in assessing conserved variable residues in a subunit of a molecular complex.</p>","PeriodicalId":74189,"journal":{"name":"microLife","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10117855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9518987","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}
引用次数: 3
Osmotic stress responses and the biology of the second messenger c-di-AMP in Streptomyces. 链霉菌渗透胁迫反应及第二信使c-二- amp的生物学研究。
microLife Pub Date : 2023-01-01 DOI: 10.1093/femsml/uqad020
Sukanya Bhowmick, Mary L Shenouda, Natalia Tschowri
{"title":"Osmotic stress responses and the biology of the second messenger c-di-AMP in <i>Streptomyces</i>.","authors":"Sukanya Bhowmick,&nbsp;Mary L Shenouda,&nbsp;Natalia Tschowri","doi":"10.1093/femsml/uqad020","DOIUrl":"https://doi.org/10.1093/femsml/uqad020","url":null,"abstract":"<p><p><i>Streptomyces</i> are prolific antibiotic producers that thrive in soil, where they encounter diverse environmental cues, including osmotic challenges caused by rainfall and drought. Despite their enormous value in the biotechnology sector, which often relies on ideal growth conditions, how <i>Streptomyces</i> react and adapt to osmotic stress is heavily understudied. This is likely due to their complex developmental biology and an exceptionally broad number of signal transduction systems. With this review, we provide an overview of <i>Streptomyces</i>' responses to osmotic stress signals and draw attention to open questions in this research area. We discuss putative osmolyte transport systems that are likely involved in ion balance control and osmoadaptation and the role of alternative sigma factors and two-component systems (TCS) in osmoregulation. Finally, we highlight the current view on the role of the second messenger c-di-AMP in cell differentiation and the osmotic stress responses with specific emphasis on the two models, <i>S. coelicolor</i> and <i>S. venezuelae</i>.</p>","PeriodicalId":74189,"journal":{"name":"microLife","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10117811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9522026","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}
引用次数: 1
Local signaling enhances output specificity of bacterial c-di-GMP signaling networks. 局部信号增强了细菌c-di-GMP信号网络的输出特异性。
microLife Pub Date : 2023-01-01 DOI: 10.1093/femsml/uqad026
Eike H Junkermeier, Regine Hengge
{"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<sub>d</sub>'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":null,"pages":null},"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}
引用次数: 1
Control of light-dependent behaviour in cyanobacteria by the second messenger cyclic di-GMP. 第二信使环二gmp对蓝藻光依赖性行为的控制。
microLife Pub Date : 2023-01-01 DOI: 10.1093/femsml/uqad019
Gen Enomoto, Thomas Wallner, Annegret Wilde
{"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":null,"pages":null},"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}
引用次数: 2
The mysterious diadenosine tetraphosphate (AP4A). 神秘的四磷酸二腺苷(AP4A)
microLife Pub Date : 2023-01-01 DOI: 10.1093/femsml/uqad016
Victor Zegarra, Christopher-Nils Mais, Johannes Freitag, Gert Bange
{"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":null,"pages":null},"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}
引用次数: 0
Recent advances and perspectives in nucleotide second messenger signaling in bacteria. 细菌中核苷酸第二信使信号的研究进展与展望。
microLife Pub Date : 2023-01-01 DOI: 10.1093/femsml/uqad015
Regine Hengge, Mihaela Pruteanu, Jörg Stülke, Natalia Tschowri, Kürşad Turgay
{"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":null,"pages":null},"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}
引用次数: 6
Small regulatory RNAs in Vibrio cholerae. 霍乱弧菌中的小调控rna。
microLife Pub Date : 2023-01-01 DOI: 10.1093/femsml/uqad030
Rabea Ghandour, Kai Papenfort
{"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":null,"pages":null},"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}
引用次数: 0
(p)ppGpp and moonlighting RNases influence the first step of lipopolysaccharide biosynthesis in Escherichia coli. (p)ppGpp和兼职rna酶影响大肠杆菌脂多糖生物合成的第一步。
microLife Pub Date : 2023-01-01 DOI: 10.1093/femsml/uqad031
Simon Brückner, Fabian Müller, Laura Schadowski, Tyll Kalle, Sophia Weber, Emily C Marino, Blanka Kutscher, Anna-Maria Möller, Sabine Adler, Dominik Begerow, Wieland Steinchen, Gert Bange, Franz Narberhaus
{"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":null,"pages":null},"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}
引用次数: 0
Cyclic di-AMP, a multifaceted regulator of central metabolism and osmolyte homeostasis in Listeria monocytogenes. 环状二磷酸腺苷,单核增生李斯特菌中心代谢和渗透平衡的多方面调节因子。
microLife Pub Date : 2023-01-01 DOI: 10.1093/femsml/uqad005
Inge Schwedt, Mengyi Wang, Johannes Gibhardt, Fabian M Commichau
{"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":null,"pages":null},"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}
引用次数: 2
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