Signal amplification of glucosamine-6-phosphate based on ribozyme glmS

Zhao, You Xing; Chen, Haodong; Du, Feng; Yasmeen, Aneela; Dong, Juan; Cui, Xin; Tang, Zhuo

doi:10.1016/j.bios.2014.06.067

Cited by 6 publications

(3 citation statements)

References 26 publications

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“…Switching of the ribozyme and DNAzyme activity through duplex-quadruplex structural transition with K + , Na + , ATP, oligo DNA, and proteins has been reported by several groups including ours [10,[15][16][17][18][19][20][21]. To the best of our knowledge, however, our QHR-QCS system is the first one that involves switching of the ribozyme activity through duplex -G-quadruplex transition in response to K + without annealing treatment.…”

Section: Relationship With Previous Studies and The Possibility Of Apmentioning

confidence: 73%

K+-responsive off-to-on switching of hammerhead ribozyme through dual G-quadruplex formation requiring no heating and cooling treatment

Yamaoki

Nagata

Mashima

et al. 2015

Biochemical and Biophysical Research Communications

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Functional RNAs that switch their activities in response to K(+) may sense the intracellular (100 mM) and extracellular (5 mM) K(+) concentrations and regulate their functions accordingly. Previously, we developed a quadruplex hammerhead ribozyme (QHR) whose conformational change, from a duplex to a G-quadruplex, triggered by K(+) results in expression of the activity. However, this QHR required heating and cooling treatment (annealing) to induce the K(+)-responsive conformational change and activity. Here, we developed a new quadruplex hammerhead ribozyme (QHR) system that does not require annealing to induce the K(+)-responsive conformational change and activity. This system is composed of QHR and a G-quadruplex-forming complementary DNA strand (QCS). In the absence of K(+), QCS formed a duplex with QHR, which suppressed the residual activity. Upon elevation of the K(+) concentration, QCS dissociated from QHR was trapped in a G-quadruplex, and then QHR could form a G-quadruplex and exerted the activity. The 11.6-fold higher activity was induced by K(+) with an EC50 value of 23 mM, but not by Na(+), which is desirable when the activity switching between the intra-/extracellular environment is aimed at. This is the first report of the activation of functional RNA through a 'dual G-quadruplex formation system'.

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Section: Relationship With Previous Studies and The Possibility Of Apmentioning

confidence: 73%

K+-responsive off-to-on switching of hammerhead ribozyme through dual G-quadruplex formation requiring no heating and cooling treatment

Yamaoki

Nagata

Mashima

et al. 2015

Biochemical and Biophysical Research Communications

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“…The effect of combination therapy on lipopolysaccharide and peptidoglycan metabolic pathways occurred earlier than that in monotherapy ( Table 3 ). The combination of polymyxin-B/amikacin/sulbactam reduced the level of glucosamine-6-phosphate (GlcN6P), UDP-Glc and UDP-GlcA, which are important metabolites and precursors of glycosylated protein and lipid biosynthesis and related to cell wall maintenance ( Zhao et al, 2014 ; Warth et al, 2015 ; Kuang et al, 2016 ). This may be due to the effect of sulbactam, since sulbactam can disintegrate the cell wall of A. baumannii , allowing companion antibiotics to enter the bacterial cell ( Horii et al, 2002 ; Penwell et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Metabolomics revealed mechanism for the synergistic effect of sulbactam, polymyxin-B and amikacin combination against Acinetobacter baumannii

et al. 2023

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IntroductionThe emergence of multidrug-resistant (MDR) Acinetobacter baumannii prompts clinicians to consider treating these infections with polymyxin combination.MethodsMetabolomic analysis was applied to investigate the synergistic effects of polymyxin-B, amikacin and sulbactam combination therapy against MDR A. baumannii harboring OXA-23 and other drug resistant genes. The drug concentrations tested were based on their clinical breakpoints: polymyxin-B (2 mg/L), amikacin (16 mg/L), polymyxin-B/amikacin (2/16 mg/L), and polymyxin-B/amikacin/sulbactam (2/16/4 mg/L).ResultsThe triple antibiotic combination significantly disrupted levels of metabolites involved in cell outer membrane structure including fatty acids, glycerophospholipids, nucleotides, amino acids and peptides as early as 15 min after administration. Amikacin and polymyxin-B alone perturbed a large number of metabolites at 15 min and 1 h, respectively, but the changes in metabolites were short-lived lasting for less than 4 h. In contrast, the combination treatment disrupted a large amount of metabolites beyond 4 h. Compared to the double-combination, the addition of sulbactam to polymyxin-B/amikacin combination produce a greater disorder in A. baumannii metabolome that further confer susceptibility of bacteria to the antibiotics.ConclusionThe metabolomic analysis identified mechanisms responsible for the synergistic activities of polymyxin-B/amikacin/sulbactam against MDR A. baumannii.

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“…1‐Position modified analogs are mainly 1‐deoxyglucosamine‐6‐phosphate (compound 1 ) and its derivatives. (Figure ) The method for determining the effects of various GlcN6P analogs on the self‐cleavage activity of a 200‐nucleotide the glmS riboswitch constructed from B. cereus was used to evaluate the molecular recognition characteristics of the glmS riboswitch . Yields of the riboswitch self‐cleavage actions were used for confirming whether the analogs could activate the self‐cleavage of the riboswitch, and the observed rate constant ( K obs ) was used for measuring the speed or efficiency for inducing the self‐cleavage .…”

Section: The Glms Riboswitch Activatorsmentioning

confidence: 95%

Recent Development of Glucosamine‐6‐phosphate Derivatives as Potential Antibacterial Agents

Liu

2020

ChemistrySelect

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The glmS riboswitch (glucosamine-6-phosphate activated riboswitch) is located at the 5'-untranslated region of the glmS mRNA, which carries the gene of glucosamine-6-phosphate (GlcN6P) synthetase named amidotransferase. The glmS riboswitch can bind to its natural coenzyme GlcN6P and lead to its own self-cleavage, causing the decrease in the expression of the glmS RNA and the synthesis of amidotransferase, and finally, reducing the production of GlcN6P. Since GlcN6P is of vital importance in the metabolic pathway of the bacterial cell wall synthesis, the glmS riboswitch gradually becomes a promising target of antibiotic drugs. In this review, an overview of the development of the glmS riboswitch activators as novel and potent antibacterial agents is described, which involves the structure of the glmS riboswitch and its self-cleavage mechanism, various the glmS riboswitch activators and their structure-activity relationships. In particular, the analogs of GlcN6P that can induce self-cleavage of the glmS riboswitch are highlighted. The most promising compound 9 (Carba-GlcN6P) exhibited not only excellent activity in inducing the selfcleavage of the glmS riboswitch, but also great efficacy (k obs = 0.153 min À 1 ) at 200 μM compared to GlcN6P (k obs = 0.177 min À 1 ).

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Signal amplification of glucosamine-6-phosphate based on ribozyme glmS

Cited by 6 publications

References 26 publications

K+-responsive off-to-on switching of hammerhead ribozyme through dual G-quadruplex formation requiring no heating and cooling treatment

K+-responsive off-to-on switching of hammerhead ribozyme through dual G-quadruplex formation requiring no heating and cooling treatment

Metabolomics revealed mechanism for the synergistic effect of sulbactam, polymyxin-B and amikacin combination against Acinetobacter baumannii

Recent Development of Glucosamine‐6‐phosphate Derivatives as Potential Antibacterial Agents

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