Two DHH Subfamily 1 Proteins in Streptococcus pneumoniae Possess Cyclic Di-AMP Phosphodiesterase Activity and Affect Bacterial Growth and Virulence

Bai, Yang; Yang, Jun; Eisele, Leslie E.; Underwood, Adam J.; Koestler, Benjamin J.; Waters, Christopher M.; Metzger, Dennis W.; Bai, Guangchun

doi:10.1128/jb.00769-13

Cited by 133 publications

(276 citation statements)

References 63 publications

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“…1C), with Co 2ϩ -associated catalytic activity being as twice high as that of Mn 2ϩ . In contrast, Streptococcus pneumoniae Pde2 binding Mn 2ϩ has the highest efficiency (16). The enzymatic activity of Rv2837c adapts to a broad pH range ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…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). M. tuberculosis does not have HD-GYP domain protein and seems lack an essential link in c-di-GMP metabolism (41).…”

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

confidence: 99%

“…They all hydrolyze c-di-AMP into linear dinucleotide 5Ј-pApA. There is also a PDE family that only contains a standalone DHH-DHHA1 domain, they hydrolyze c-di-AMP in a two-step process: first to linear 5Ј-pApA, which is subsequently hydrolyzed into two 5Ј-AMP molecules (16,17,20). All types of PDE enzymes require ions for catalytic activity.…”

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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: Resultsmentioning

confidence: 99%

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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“…In recent years, c-di-AMP has been identified as a major second messenger (reviewed in reference 141). c-di-AMP is synthetized from two molecules of ATP by diadenylyl cyclases (DACs), and it is degraded to pApA or AMP by phosphodiesterases (PDEs) (142,143).…”

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

511

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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“…In Bacillus subtilis, bacterial c-di-AMP levels are reduced in response to DNA damage, resulting in delayed sporulation (Oppenheimer-Shaanan et al, 2011). High c-di-AMP levels result in smaller bacterial size in Staphylococcus aureus (Corrigan et al, 2011), c-di-AMP secreted by Listeria monocytogenes triggers a cytosolic pathway for innate immunity (Woodward et al, 2010), and c-di-AMP homeostasis is required for the virulence of Streptococcus pyogenes and Streptococcus pneumonia (Bai et al, 2013;Cho and Kang, 2013;Witte et al, 2013). c-di-AMP is synthesized by a protein containing a diadenylate cyclase domain (DAC domain).…”

Section: Introductionmentioning

confidence: 99%

Diadenylate cyclase evaluation of ssDacA (SSU98_1483) in Streptococcus suis serotype 2

Du¹,

Sun²

2015

Genet. Mol. Res.

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ABSTRACT. Cyclic diadenosine monophosphate is a recently identified signaling molecule. It has been shown to play important roles in bacterial pathogenesis. SSU98_1483 (ssDacA), which is an ortholog of Listeria monocytogenes DacA, is a putative diadenylate cyclase in Streptococcus suis serotype 2. In this study, we determined the enzymatic activity of ssDacA in vitro using high-performance liquid chromatography and mass spectrometry. Our results showed that ssDacA was a diadenylate cyclase that converts ATP into cyclic diadenosine monophosphate in vitro. The diadenylate cyclase activity of ssDacA was dependent on divalent metal ions such as Mg , and it is more active under basic pH than under acidic pH. The conserved RHR motif in ssDacA was essential for its enzymatic activity, and mutation in this motif abolished the diadenylate cyclase activity of ssDacA. These results indicate that ssDacA is a diadenylate cyclase, which synthesizes cyclic diadenosine monophosphate in Streptococcus suis serotype 2.

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Two DHH Subfamily 1 Proteins in Streptococcus pneumoniae Possess Cyclic Di-AMP Phosphodiesterase Activity and Affect Bacterial Growth and Virulence

Cited by 133 publications

References 63 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

Diadenylate cyclase evaluation of ssDacA (SSU98_1483) in Streptococcus suis serotype 2

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