Inhibition of Staphylococcus aureus PriA Helicase by Flavonol Kaempferol

Huang, Yen‐Hua; Huang, Chien-Chih; Chen, Cheng‐Chieh; Yang, Kai-Jr; Huang, Cheng-Yang

doi:10.1007/s10930-015-9609-y

Cited by 47 publications

(37 citation statements)

References 31 publications

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“…Further study showed that the ATPase activity of this helicase KpDnaB was decreased to 75% and 65% in the presence of quercetin and kaempferol, respectively [83]. In the next work, Huang et al [84] observed that kaempferol inhibits the DNA PriA helicase of S. aureus, and these results showed that the concentration of phosphate from ATP hydrolysis by this DNA helicase was decreased to 37% in the presence of 35 µM kaempferol. Thus, it was summarized that kaempferol can bind to DNA helicase and then inhibit its ATPase activity and this is a new mechanism of action for this chemical compound.…”

Section: Discussionmentioning

confidence: 84%

“…Thus, it was summarized that kaempferol can bind to DNA helicase and then inhibit its ATPase activity and this is a new mechanism of action for this chemical compound. According to the results, this flavonol may be taken into consideration as an active natural molecule in the development of new antibiotics against S. aureus [84]. Currently, Huang [73] demonstrated the inhibitory effect of kaempferol on the activity of a dihydropyrimidinase from P. aeruginosa with the IC 50 value of 50 ± 2 µM.…”

Section: Discussionmentioning

confidence: 96%

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Antibacterial Activity of Some Flavonoids and Organic Acids Widely Distributed in Plants

Adamczak

Ożarowski

Karpiński

2019

JCM

342

196

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Among natural substances widespread in fruits, vegetables, spices, and medicinal plants, flavonoids and organic acids belong to the promising groups of bioactive compounds with strong antioxidant and anti-inflammatory properties. The aim of the present work was to evaluate the antibacterial activity of 13 common flavonoids (flavones, flavonols, flavanones) and 6 organic acids (aliphatic and aromatic acids). The minimal inhibitory concentrations (MICs) of selected plant substances were determined by the micro-dilution method using clinical strains of four species of pathogenic bacteria. All tested compounds showed antimicrobial properties, but their biological activity was moderate or relatively low. Bacterial growth was most strongly inhibited by salicylic acid (MIC = 250–500 μg/mL). These compounds were generally more active against Gram-negative bacteria: Escherichia coli and Pseudomonas aeruginosa than Gram-positive ones: Enterococcus faecalis and Staphylococcus aureus. An analysis of the antibacterial effect of flavone, chrysin, apigenin, and luteolin showed that the presence of hydroxyl groups in the phenyl rings A and B usually did not influence on the level of their activity. A significant increase in the activity of the hydroxy derivatives of flavone was observed only for S. aureus. Similarly, the presence and position of the sugar group in the flavone glycosides generally had no effect on the MIC values.

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Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 96%

Antibacterial Activity of Some Flavonoids and Organic Acids Widely Distributed in Plants

Adamczak

Ożarowski

Karpiński

2019

JCM

342

196

View full text Add to dashboard Cite

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“…DMY achieved bactericidal activity by dual effects of cell membrane damage and DNA binding (Wu, Bai, Zhong, Huang, & Gao, 2017). However, in the study of Huang, Huang, Chen, Yang, and Huang (2015), the effect of DMY on the inhibition of S. aureus PriA (SaPriA), an essential helicase for DNA replication restart, was not so significant. Furthermore, Huang (2015) investigated the inhibitory effect of DMY on dihydropyrimidinase, a key member in the chain of pyrimidine catabolism and metabolism of DNA base in Pseudomonas aeruginosa.…”

Section: Antimicrobial and Antiviral Activitymentioning

confidence: 99%

Dihydromyricetin: A review on identification and quantification methods, biological activities, chemical stability, metabolism and approaches to enhance its bioavailability

Liú

Mao

Ding

et al. 2019

Trends in Food Science & Technology

106

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Background: Dihydromyricetin (DMY) is an important plant flavonoid, which has received great attention due to its health-benefiting activities, including antioxidant, antimicrobial, anti-inflammatory, anticancer, antidiabetic and neuroprotective activities. DMY capsules have been sold in US as a nutraceutical supplement to prevent alcoholic hangovers. The major disadvantage associated with DMY is its chemical instability and poor bioavailability caused by the combined effects of its low solubility and poor membrane permeability. This limits its practical use in the food and pharmaceutical fields. Scope and approach: The present paper gives an overview of the current methods for the identification and quantification of DMY. Furthermore, recent findings regarding the main biological properties and chemical stability of DMY, the metabolism of DMY as well as different approaches to increase DMY bioavailability in both aqueous and lipid phases are discussed. Key findings and conclusions: Current trends on identification and quantification of DMY have been focused on spectral and chromatographic techniques. Many factors such as heat, pH, metal ions, could affect the chemical stability of DMY. Despite the diverse biological effects of DMY, DMY faces with the problem of poor bioavailability. Utilization of different delivery systems including solid dispersion, nanocapsule, microemuslion, cyclodextrin inclusion complexes, co-crystallization, phospholipid complexes, and chemical or enzymatic acylation has the potential to improve both the solubility and bioavailability. DMY digested in laboratory animals undergoes reduction, dehydroxylation, methylation, glucuronidation, and sulfation. Novel DMY delivery systems and basic pharmacokinetic studies of encapsulated DMY on higher animals and humans might be required in the future.

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“…Construction of the SaDnaD [ 58 ], SaPriA [ 59 ], Klebsiella pneumoniae SSB (KpSSB) [ 60 ], and tag-free KpSSB [ 61 ] expression plasmids has been reported. The gene encoding SaSsbA (the accession number ACY10277) was amplified by PCR using the genomic DNA of S .…”

Section: Methodsmentioning

confidence: 99%

“…Purification of the recombinant SaDnaD [ 58 ], SaPriA [ 59 ], KpSSB [ 60 ], and tag-free KpSSB [ 61 ] has been reported. The recombinant SaSsbA and KpSSBc were expressed and purified using the protocol described previously for PriB [ 63 ].…”

Section: Methodsmentioning

confidence: 99%

Staphylococcus aureus single-stranded DNA-binding protein SsbA can bind but cannot stimulate PriA helicase

et al. 2017

Self Cite

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Single-stranded DNA-binding protein (SSB) and PriA helicase play important roles in bacterial DNA replication restart process. The mechanism by which PriA helicase is bound and stimulated by SSB in Escherichia coli (Ec) has been established, but information on this process in Gram-positive bacteria are limited. We characterized the properties of SSB from Staphylococcus aureus (SaSsbA, a counterpart of EcSSB) and analyzed its interaction with SaPriA. The gel filtration chromatography analysis of purified SaSsbA showed a stable tetramer in solution. The crystal structure of SaSsbA determined at 1.82 Å resolution (PDB entry 5XGT) reveals that the classic oligonucleotide/oligosaccharide-binding folds are formed in the N-terminal DNA-binding domain, but the entire C-terminal domain is disordered. Unlike EcSSB, which can stimulate EcPriA via a physical interaction between EcPriA and the C-terminus of EcSSB (SSB-Ct), SaSsbA does not affect the activity of SaPriA. We also found that SaPriA can be bound by SaSsbA, but not by SaSsbA-Ct. Although no effect was found with SaSsbA, SaPriA can be significantly stimulated by the Gram-negative Klebsiella pneumoniae SSB (KpSSB). In addition, we found that the conserved SSB-Ct binding site of KpPriA (Trp82, Tyr86, Lys370, Arg697, and Gln701) is not present in SaPriA. Arg697 in KpPriA is known to play a critical role in altering the SSB35/SSB65 distribution, but this corresponding residue in SaPriA is Glu767 instead, which has an opposite charge to Arg. SaPriA E767R mutant was constructed and analyzed; however, it still cannot be stimulated by SaSsbA. Finally, we found that the conserved MDFDDDIPF motif in the Gram-negative bacterial SSB is DISDDDLPF in SaSsbA, i.e., F172 in EcSSB and F168 in KpSSB is S161 in SaSsbA, not F. When acting with SaSsbA S161F mutant, the activity of SaPriA was dramatically enhanced elevenfold. Overall, the conserved binding sites, both in EcPriA and EcSSB, are not present in SaPriA and SaSsbA, thereby no stimulation occurs. Our observations through structure-sequence comparison and mutational analyses indicate that the case of EcPriA-EcSSB is not applicable to SaPriA-SaSsbA because of inherent differences among the species.

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Inhibition of Staphylococcus aureus PriA Helicase by Flavonol Kaempferol

Cited by 47 publications

References 31 publications

Antibacterial Activity of Some Flavonoids and Organic Acids Widely Distributed in Plants

Antibacterial Activity of Some Flavonoids and Organic Acids Widely Distributed in Plants

Dihydromyricetin: A review on identification and quantification methods, biological activities, chemical stability, metabolism and approaches to enhance its bioavailability

Staphylococcus aureus single-stranded DNA-binding protein SsbA can bind but cannot stimulate PriA helicase

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