Cyclic di-GMP: the First 25 Years of a Universal Bacterial Second Messenger
Reads0
Chats0
TLDR
A historic perspective on the development of the field is provided, common trends are emphasized, and new directions in c-di-GMP research are highlighted that will give a deeper understanding of this truly universal bacterial second messenger.Abstract:
SUMMARY Twenty-five years have passed since the discovery of cyclic dimeric (3′→5′) GMP (cyclic di-GMP or c-di-GMP). From the relative obscurity of an allosteric activator of a bacterial cellulose synthase, c-di-GMP has emerged as one of the most common and important bacterial second messengers. Cyclic di-GMP has been shown to regulate biofilm formation, motility, virulence, the cell cycle, differentiation, and other processes. Most c-di-GMP-dependent signaling pathways control the ability of bacteria to interact with abiotic surfaces or with other bacterial and eukaryotic cells. Cyclic di-GMP plays key roles in lifestyle changes of many bacteria, including transition from the motile to the sessile state, which aids in the establishment of multicellular biofilm communities, and from the virulent state in acute infections to the less virulent but more resilient state characteristic of chronic infectious diseases. From a practical standpoint, modulating c-di-GMP signaling pathways in bacteria could represent a new way of controlling formation and dispersal of biofilms in medical and industrial settings. Cyclic di-GMP participates in interkingdom signaling. It is recognized by mammalian immune systems as a uniquely bacterial molecule and therefore is considered a promising vaccine adjuvant. The purpose of this review is not to overview the whole body of data in the burgeoning field of c-di-GMP-dependent signaling. Instead, we provide a historic perspective on the development of the field, emphasize common trends, and illustrate them with the best available examples. We also identify unresolved questions and highlight new directions in c-di-GMP research that will give us a deeper understanding of this truly universal bacterial second messenger.read more
Citations
More filters
Journal ArticleDOI
Direct Activation of STING in the Tumor Microenvironment Leads to Potent and Systemic Tumor Regression and Immunity
Leticia Corrales,Laura Hix Glickman,Sarah M. McWhirter,David B. Kanne,Kelsey E. Sivick,George E. Katibah,Seng-Ryong Woo,Edward E. Lemmens,Tamara Banda,Justin Leong,Ken Metchette,Thomas W. Dubensky,Thomas F. Gajewski +12 more
TL;DR: It injection of STING agonists induced profound regression of established tumors in mice and generated substantial systemic immune responses capable of rejecting distant metastases and providing long-lived immunologic memory.
Journal ArticleDOI
Molecular mechanisms of biofilm-based antibiotic resistance and tolerance in pathogenic bacteria
Clayton W. Hall,Thien-Fah Mah +1 more
TL;DR: This review summarises both historical and recent scientific data in support of the known biofilm resistance and tolerance mechanisms and suggestions for future work in the field are provided.
Journal ArticleDOI
Pseudomonas aeruginosa Lifestyle: A Paradigm for Adaptation, Survival, and Persistence.
TL;DR: The central regulatory role of quorum sensing and signaling systems by nucleotide-based second messengers resulting in different lifestyles of P. aeruginosa is reviewed and various regulatory proteins will be discussed which form a plethora of controlling systems acting at transcriptional level for timely expression of genes enabling rapid responses to external stimuli and unfavorable conditions.
Journal ArticleDOI
Cyclic [G(2′,5′)pA(3′,5′)p] Is the Metazoan Second Messenger Produced by DNA-Activated Cyclic GMP-AMP Synthase
Pu Gao,Manuel Ascano,Wu Yang,Winfried Barchet,Barbara L. Gaffney,Thomas Zillinger,Artem A. Serganov,Liu Yizhou,Roger A. Jones,Gunther Hartmann,Thomas Tuschl,Dinshaw J. Patel +11 more
TL;DR: Structural, chemical, biochemical, and cellular assays are combined to demonstrate that this second messenger contains G(2',5')pA and A(3',5']pG phosphodiester linkages, designated c[G(2,5')sDNA binding, cGAS] as a founding member of a family of metazoan 2',5'-containing cyclic heterodinucleotide second messengers distinct from bacterial 3',5' cyclic dinucleotides
Journal ArticleDOI
Strategies for combating bacterial biofilms: A focus on anti-biofilm agents and their mechanisms of action
TL;DR: The molecules considered here might be used to treat biofilm-associated infections after significant structural modifications, thereby investigating its effective delivery in the host and minimum effective concentration must be capable of eradicating biofilm infections with maximum potency without posing any adverse side effects on the host.
References
More filters
Journal ArticleDOI
The bacterial second messenger c-di-GMP: mechanisms of signalling
TL;DR: In this article, a review highlights important questions in research into the mechanisms of cyclic-di-GMP signalling and its role in bacterial physiology and highlights the importance of protein-protein interactions.
Journal ArticleDOI
Cyclic Di-GMP Stimulates Protective Innate Immunity in Bacterial Pneumonia
David K. R. Karaolis,Michael W. Newstead,Xianying Zeng,Mamoru Hyodo,Yoshihiro Hayakawa,Urvhashi Bhan,Hallie Liang,Theodore J. Standiford +7 more
TL;DR: It is proposed that the cyclic dinucleotide c-di-GMP may be used clinically as an effective immunomodulator, immune enhancer, and vaccine adjuvant to protect against respiratory infection and pneumonia in humans and animals.
Journal ArticleDOI
The flagellar sigma factor FliA (sigma(28)) regulates the expression of Salmonella genes associated with the centisome 63 type III secretion system.
Katrin Eichelberg,Jorge E. Galán +1 more
TL;DR: There is an overlap between regulatory mechanisms that control flagellar and type III secretion gene expression in Salmonella serovar Typhi, indicating that the effects of mutations in flageLLar genes on the phenotypes associated with the SPI-1 type III protein secretion system are not uniform.
Journal ArticleDOI
The EpsE Flagellar Clutch Is Bifunctional and Synergizes with EPS Biosynthesis to Promote Bacillus subtilis Biofilm Formation
TL;DR: The transition from motility to biofilm formation may be governed by a single bifunctional enzyme, and both functions of EpsE synergize to stabilize cell aggregates and relieve selective pressure to abolish motility by genetic mutation.
Journal ArticleDOI
Coordinated Cyclic-Di-GMP Repression of Salmonella Motility through YcgR and Cellulose
Violeta Zorraquino,Begoña García,Cristina Latasa,Maite Echeverz,Alejandro Toledo-Arana,Jaione Valle,Iñigo Lasa,Cristina Solano +7 more
TL;DR: The results highlight the relevance of cellulose in Salmonella lifestyle switching as an architectural element that is both essential for biofilm development and required, in collaboration with YcgR, for complete motility inhibition.