Synergistic antibacterial activity of baicalin and EDTA in combination with colistin against colistin-resistant Salmonella

Cui, Xiaodie; Zhang, Junkai; Sun, Yi-Ming; Yan, Fengbin; Zhao, Jin-Feng; He, Dongjian; Pan, Yongchu; Li, Yuan; Zhai, Yajun; Hu, Gongzheng

doi:10.1016/j.psj.2022.102346

Cited by 19 publications

(5 citation statements)

References 28 publications

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“…TCA cycle is an important metabolic pathway of bacteria and has been shown to be associated with the reversal of drug resistance of bacteria. For example, alanine restored biotic sensitivity in Xanthomonas oryzae by promoting the TCA cycle; 41 baicalin and ethylenediaminetetraacetic acid (EDTA) increased the antimicrobial effect of colistin against colistin-resistant Salmonella by accelerating the TCA cycle; 42 zeolitic imidazolate framework-8 accelerated MRSA death by disrupting the TCA cycle. 43 Therefore, to gain further insights, we detected the activities of three key enzymes belonging to the TCA cycle.…”

Section: Discussionmentioning

confidence: 99%

Effect of Three Different Amino Acids Plus Gentamicin Against Methicillin-Resistant Staphylococcus aureus

Guo¹,

Pan²,

Fan³

et al. 2023

IDR

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Background The issue of methicillin-resistant Staphylococcus aureus (MRSA) resistant to many antibiotics and causing serious infectious diseases is a growing healthcare concern. Purpose In recent years, exogenous administration of metabolites in combination with antibiotics can re-sensitize resistant bacteria to antibiotics; however, their effects vary, and their underlying mechanism of action remains elusive. Methods We assessed the bactericidal effects of the three amino acids in combination with gentamicin in vitro and in vivo. Subsequently, we explored the role of these amino acids on the metabolomics of MRSA using Liquid chromatography-tandem mass spectrometry (LC-MS/MS). Furthermore, we performed the downstream analyses using MetaboAnalyst and Interactive Pathways Explorer. Results Exogenous threonine showed the best bactericidal efficacy with gentamicin, followed by glycine, wherein serine had no effect. Amino acid treatments mainly up-regulated the metabolites, increased the amino acid abundance, and significantly activated metabolisms; these effects were consistent with the bactericidal efficacy of the three amino acids. Most amino acids participated in the tricarboxylic acid cycle, and threonine supplementation increased the activities of citrate synthase, isocitrate dehydrogenase and α-ketoglutarate dehydrogenase, whereas glycine increased activities of citrate synthase and α-ketoglutarate dehydrogenase, and serine did not affect the activities of any of the three key enzymes. We identified 24 biomarkers in the three groups, among which glutamic acid and cysteine showed a gradient decrease and increase, respectively. Subsequent analyses revealed that glutamic acid but not cysteine promoted the bactericidal effect of gentamicin synergistically. Conclusion Threonine has the best synergistic effect in reversing bacterial resistance compared to glycine and serine. We show that different amino acids combined with an antibiotic mainly affect amino acid metabolism and act via different metabolic regulatory mechanisms, which could help develop effective strategies for tackling MRSA infections.

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Section: Discussionmentioning

confidence: 99%

Effect of Three Different Amino Acids Plus Gentamicin Against Methicillin-Resistant Staphylococcus aureus

Guo¹,

Pan²,

Fan³

et al. 2023

IDR

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“…The fractional inhibitory concentration index ( FICI ) was calculated using the formula: FICI = (MIC of drug A in combination/MIC of drug A alone) + (MIC of drug B in combination/MIC of drug B alone). Based on the FICI values, the effects were classified as follows: Synergy effect: FICI ≤ 0.5; Additivity effect: FICI >0.5 and ≤1; Irrelevance effect: FICI >1 and ≤2; Antagonistic effect: FICI >2 ( Cui et al., 2023 ).…”

Section: Methodsmentioning

confidence: 99%

Effects of chitooligosaccharide on the in vitro antibacterial activity against avian Escherichia coli and the pharmacokinetics of florfenicol in healthy chickens

Zhang,

Li,

Duan

et al. 2024

Poultry Science

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“…According to Cui et al [ 140 ], the combination of EDTA and Baicalin (a compound from Scutellaria baicalensis (a herbal Chinese medicine)) could restore colistin efficacy against several colistin-resistant Salmonella isolates recovered from poultry and humans by directly inhibiting the production of MCR-1. Molecular docking analysis revealed a strong interaction between baicalin and several residues of MCR-1 (Lys307, Lys333, Asp331, Asp337, Gly334, and Tyr308), whereas EDTA, a strong metal chelating agent, was proposed to chelate the Zn 2+ in the active site of MCR-1 [ 140 ].…”

Section: Progress In Drug Development Of Pea Transferase Inhibitorsmentioning

confidence: 99%

Phosphoethanolamine Transferases as Drug Discovery Targets for Therapeutic Treatment of Multi-Drug Resistant Pathogenic Gram-Negative Bacteria

Thai,

Stubbs,

Sarkar-Tyson

et al. 2023

Antibiotics

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Antibiotic resistance caused by multidrug-resistant (MDR) bacteria is a major challenge to global public health. Polymyxins are increasingly being used as last-in-line antibiotics to treat MDR Gram-negative bacterial infections, but resistance development renders them ineffective for empirical therapy. The main mechanism that bacteria use to defend against polymyxins is to modify the lipid A headgroups of the outer membrane by adding phosphoethanolamine (PEA) moieties. In addition to lipid A modifying PEA transferases, Gram-negative bacteria possess PEA transferases that decorate proteins and glycans. This review provides a comprehensive overview of the function, structure, and mechanism of action of PEA transferases identified in pathogenic Gram-negative bacteria. It also summarizes the current drug development progress targeting this enzyme family, which could reverse antibiotic resistance to polymyxins to restore their utility in empiric therapy.

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Synergistic antibacterial activity of baicalin and EDTA in combination with colistin against colistin-resistant Salmonella

Cited by 19 publications

References 28 publications

Effect of Three Different Amino Acids Plus Gentamicin Against Methicillin-Resistant Staphylococcus aureus

Effect of Three Different Amino Acids Plus Gentamicin Against Methicillin-Resistant Staphylococcus aureus

Effects of chitooligosaccharide on the in vitro antibacterial activity against avian Escherichia coli and the pharmacokinetics of florfenicol in healthy chickens

Phosphoethanolamine Transferases as Drug Discovery Targets for Therapeutic Treatment of Multi-Drug Resistant Pathogenic Gram-Negative Bacteria

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