Dataset Information

Antibacterial Activity of Juglone against Staphylococcus aureus: From Apparent to Proteomic.

ABSTRACT: The proportion of foodborne disease caused by pathogenic microorganisms is rising worldwide, with staphylococcal food poisoning being one of the main causes of this increase. Juglone is a plant-derived 1,4-naphthoquinone with confirmed antibacterial and antitumor activities. However, the specific mechanism underlying its antibacterial activity against Staphylococcus aureus remains unclear. To elucidate the mechanism underlying its antibacterial activity, isobaric tags for relative and absolute quantitation methods of quantitative proteomics were applied for analysis of the 53 proteins that were differentially expressed after treatment with juglone. Combined with verification experiments, such as detection of changes in DNA and RNA content and quantification of oxidative damage, our results suggested that juglone effectively increased the protein expression of oxidoreductase and created a peroxidative environment within the cell, significantly reducing cell wall formation and increasing membrane permeability. We hypothesize that juglone binds to DNA and reduces DNA transcription and replication directly. This is the first study to adopt a proteomic approach to investigate the antibacterial mechanism of juglone.

SUBMITTER: Wang J

PROVIDER: S-EPMC4926497 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Antibacterial Activity of Juglone against Staphylococcus aureus: From Apparent to Proteomic.

Wang Jiayi J Cheng Yuhuan Y Wu Rina R Jiang Donghua D Bai Bing B Tan Dehong D Yan Tingcai T Sun Xiyun X Zhang Qi Q Wu Zhaoxia Z

International journal of molecular sciences 20160618 6

The proportion of foodborne disease caused by pathogenic microorganisms is rising worldwide, with staphylococcal food poisoning being one of the main causes of this increase. Juglone is a plant-derived 1,4-naphthoquinone with confirmed antibacterial and antitumor activities. However, the specific mechanism underlying its antibacterial activity against Staphylococcus aureus remains unclear. To elucidate the mechanism underlying its antibacterial activity, isobaric tags for relative and absolute q ...[more]

PMID: 27322260

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Project description:Diabetic foot infection (DFI) is a common complication in diabetes patients, with foot infections being the leading cause of amputations. Staphylococcus aureus is frequently found in diabetic foot infections, of which methicillin-resistant Staphylococcus aureus (MRSA) has become a major clinical and epidemiological challenge. Since MRSA strains are resistant to most β-lactam antibiotics, and also partially resistant to other antibiotics, treatment is difficult and costly. The emergence of drug-resistant bacteria often arises from overuse or misuse of antibiotics. Clinically, canagliflozin is commonly used for the treatment of type 2 diabetes. On this basis, we investigated the antibacterial activity and mechanism of canagliflozin against MRSA, with the aim to discover novel functions of canagliflozin and provide new insights for the treatment of MRSA. Using the microbroth dilution method to determine the half maximal inhibitory concentration of drugs, we found that canagliflozin not only can inhibit the growth of methicillin-sensitive Staphylococcus aureus (MSSA) but also exhibits antibacterial activity against MRSA. The IC50 values, at approximately 56.01 μM and 57.60 μM, were almost the same. At 12 h, canagliflozin showed a significant antibacterial effect against MRSA at and above 30 μM. In addition, its combined use with penicillin achieved better antibacterial effects, which were increased by about three times. Additive antibacterial activity (FICI = 0.69) was found between penicillin and canagliflozin, which was better than that of doxycycline and canagliflozin (FICI = 0.95). Canagliflozin also affected bacterial metabolic markers, such as glucose, ATP, and lactic acid. The results of crystal violet staining indicate that canagliflozin disrupted the formation of bacterial biofilm. Our electron microscopy results showed that canagliflozin distorted the bacterial cell wall. The results of RT-PCR suggest that canagliflozin down-regulated the expressions of biofilm-related gene (clfA, cna, agrC, mgrA, hld) and methicillin-resistance gene (mecA), which was related to MRSA. Molecular docking also indicated that canagliflozin affected some interesting targets of MRSA, such as the sarA, crtM and fnbA proteins. In conclusion, canagliflozin exhibits antibacterial activity against MRSA by affecting bacterial metabolism, inhibiting its biofilm formation, distorting the bacterial cell wall, and altering the gene expression of biofilm formation and its virulence. Our study reveals the antibacterial activity of canagliflozin against MRSA, providing a new reference for treating diabetic foot infections.

Dataset Information

Antibacterial Activity of Juglone against Staphylococcus aureus: From Apparent to Proteomic.

Publications

Antibacterial Activity of Juglone against Staphylococcus aureus: From Apparent to Proteomic.

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