cAMP, c-di-GMP, c-di-AMP and now cGMP: bacteria use them all!

Gomelsky, Mark

doi:10.1111/j.1365-2958.2010.07514.x

Cited by 150 publications

(151 citation statements)

References 15 publications

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“…Rv2837c May Regulate Both c-di-AMP and c-di-GMP Signaling Pathways in M. tuberculosis-Both c-di-AMP and c-di-GMP are important intracellular signaling molecules, and their homeostasis processes are regulated by many proteins in bacteria cells (3)(4)(5). c-di-GMP is down-regulated by EAL domain and HD-GYP domain, resulting in 5Ј-pGpG and GMP, respectively (6,39), whereas c-di-AMP is broken down by stand-alone DHH-DHHA1 domain and membrane-bound DHH-DHHA1, as well as HD domain to AMP and 5Ј-pApA, respectively (16,18,40).…”

Section: The Oligomeric State Of C-di-nmps Affects Rv2837cmentioning

confidence: 99%

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Structural and Biochemical Insight into the Mechanism of Rv2837c from Mycobacterium tuberculosis as a c-di-NMP Phosphodiesterase

Wang

Liu

et al. 2016

Journal of Biological Chemistry

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The intracellular infections of Mycobacterium tuberculosis, which is the causative agent of tuberculosis, are regulated by many cyclic dinucleotide signaling. Rv2837c from M. tuberculosis is a soluble, stand-alone DHH-DHHA1 domain phosphodiesterase that down-regulates c-di-AMP through catalytic degradation and plays an important role in M. tuberculosis infections. Here, we report the crystal structure of Rv2837c (2.0 Å ), and its complex with hydrolysis intermediate 5-pApA (2.35 Å ). Our structures indicate that both DHH and DHHA1 domains are essential for c-di-AMP degradation. Further structural analysis shows that Rv2837c does not distinguish adenine from guanine, which explains why Rv2837c hydrolyzes all linear dinucleotides with almost the same efficiency. We observed that Rv2837c degraded other c-di-NMPs at a lower rate than it did on c-di-AMP. Nevertheless, our data also showed that Rv2837c significantly decreases concentrations of both c-di-AMP and c-di-GMP in vivo. Our results suggest that beside its major role in c-di-AMP degradation Rv2837c could also regulate c-di-GMP signaling pathways in bacterial cell.

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Section: The Oligomeric State Of C-di-nmps Affects Rv2837cmentioning

confidence: 99%

“…many cellular processes (3)(4)(5). c-di-GMP regulates processes such as biofilm formation, motility, virulence, cell cycle, and type I interferon stimulation (6 -9).…”

mentioning

confidence: 99%

Structural and Biochemical Insight into the Mechanism of Rv2837c from Mycobacterium tuberculosis as a c-di-NMP Phosphodiesterase

Wang

Liu

et al. 2016

Journal of Biological Chemistry

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“…and cyclic AMP-GMP) play key roles in the regulation of bacterial cell physiology (139,140). Very little is known about their role in LAB physiology.…”

Section: Cyclic Nucleotides As Second Messengers In Labmentioning

confidence: 99%

Stress Physiology of Lactic Acid Bacteria

Papadimitriou

Alegría

Bron

et al. 2016

Microbiol Mol Biol Rev

517

404

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SUMMARYLactic acid bacteria (LAB) are important starter, commensal, or pathogenic microorganisms. The stress physiology of LAB has been studied in depth for over 2 decades, fueled mostly by the technological implications of LAB robustness in the food industry. Survival of probiotic LAB in the host and the potential relatedness of LAB virulence to their stress resilience have intensified interest in the field. Thus, a wealth of information concerning stress responses exists today for strains as diverse as starter (e.g.,Lactococcus lactis), probiotic (e.g., severalLactobacillusspp.), and pathogenic (e.g.,EnterococcusandStreptococcusspp.) LAB. Here we present the state of the art for LAB stress behavior. We describe the multitude of stresses that LAB are confronted with, and we present the experimental context used to study the stress responses of LAB, focusing on adaptation, habituation, and cross-protection as well as on self-induced multistress resistance in stationary phase, biofilms, and dormancy. We also consider stress responses at the population and single-cell levels. Subsequently, we concentrate on the stress defense mechanisms that have been reported to date, grouping them according to their direct participation in preserving cell energy, defending macromolecules, and protecting the cell envelope. Stress-induced responses of probiotic LAB and commensal/pathogenic LAB are highlighted separately due to the complexity of the peculiar multistress conditions to which these bacteria are subjected in their hosts. Induction of prophages under environmental stresses is then discussed. Finally, we present systems-based strategies to characterize the “stressome” of LAB and to engineer new food-related and probiotic LAB with improved stress tolerance.

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“…Bacteria often use specific nucleotides as second messengers. These nucleotides include cyclic mononucleotides, such as cyclic AMP (cAMP) and cyclic GMP (cGMP), as well as cyclic dinucleotides, such as cyclic di-AMP (c-di-AMP), cyclic di-GMP (c-di-GMP), and (p)ppGpp (1)(2)(3).…”

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confidence: 99%

An Essential Poison: Synthesis and Degradation of Cyclic Di-AMP in Bacillus subtilis

et al. 2015

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Gram-positive bacteria synthesize the second messenger cyclic di-AMP (c-di-AMP) to control cell wall and potassium homeostasis and to secure the integrity of their DNA. In the firmicutes, c-di-AMP is essential for growth. The model organism Bacillus subtilis encodes three diadenylate cyclases and two potential phosphodiesterases to produce and degrade c-di-AMP, respectively. Among the three cyclases, CdaA is conserved in nearly all firmicutes, and this enzyme seems to be responsible for the c-di-AMP that is required for cell wall homeostasis. Here, we demonstrate that CdaA localizes to the membrane and forms a complex with the regulatory protein CdaR and the glucosamine-6-phosphate mutase GlmM. Interestingly, cdaA, cdaR, and glmM form a gene cluster that is conserved throughout the firmicutes. This conserved arrangement and the observed interaction between the three proteins suggest a functional relationship. Our data suggest that GlmM and GlmS are involved in the control of c-di-AMP synthesis. These enzymes convert glutamine and fructose-6-phosphate to glutamate and glucosamine-1-phosphate. c-di-AMP synthesis is enhanced if the cells are grown in the presence of glutamate compared to that in glutamine-grown cells. Thus, the quality of the nitrogen source is an important signal for c-di-AMP production. In the analysis of c-di-AMP-degrading phosphodiesterases, we observed that both phosphodiesterases, GdpP and PgpH (previously known as YqfF), contribute to the degradation of the second messenger. Accumulation of c-di-AMP in a gdpP pgpH double mutant is toxic for the cells, and the cells respond to this accumulation by inactivation of the diadenylate cyclase CdaA. IMPORTANCEBacteria use second messengers for signal transduction. Cyclic di-AMP (c-di-AMP) is the only second messenger known so far that is essential for a large group of bacteria. We have studied the regulation of c-di-AMP synthesis and the role of the phosphodiesterases that degrade this second messenger. c-di-AMP synthesis strongly depends on the nitrogen source: glutamategrown cells produce more c-di-AMP than glutamine-grown cells. The accumulation of c-di-AMP in a strain lacking both phosphodiesterases is toxic and results in inactivation of the diadenylate cyclase CdaA. Our results suggest that CdaA is the critical diadenylate cyclase that produces the c-di-AMP that is both essential and toxic upon accumulation. In order to process environmental information in the cell, many organisms are capable of synthesizing so-called second messengers. These small molecules are formed in response to primary signals and perceived by cellular targets. Bacteria often use specific nucleotides as second messengers. These nucleotides include cyclic mononucleotides, such as cyclic AMP (cAMP) and cyclic GMP (cGMP), as well as cyclic dinucleotides, such as cyclic di-AMP (c-di-AMP), cyclic di-GMP (c-di-GMP), and (p) ppGpp (1-3).The investigation of c-di-AMP-mediated signaling has recently attracted much attention (2). This molecule is formed by many bacteria a...

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cAMP, c-di-GMP, c-di-AMP and now cGMP: bacteria use them all!

Cited by 150 publications

References 15 publications

Structural and Biochemical Insight into the Mechanism of Rv2837c from Mycobacterium tuberculosis as a c-di-NMP Phosphodiesterase

Structural and Biochemical Insight into the Mechanism of Rv2837c from Mycobacterium tuberculosis as a c-di-NMP Phosphodiesterase

Stress Physiology of Lactic Acid Bacteria

An Essential Poison: Synthesis and Degradation of Cyclic Di-AMP in Bacillus subtilis

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