Potentiation of β-Lactams against Methicillin-Resistant Staphylococcus aureus (MRSA) Using Octyl Gallate, a Food-Grade Antioxidant

Tamang, Migma Dorji; Bae, Junghee; Park, Myungseo; Jeon, Byeonghwa

doi:10.3390/antibiotics11020266

Cited by 7 publications

(14 citation statements)

References 25 publications

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“…Our previous study shows that OG permeabilizes the bacterial cell wall in MRSA, which can increase the access of antimicrobials to the cellular targets [ 17 ]. We hypothesized that OG may increase the activity of penicillin and bacitracin against S. epidermidis by altering the permeability of the bacterial cell wall.…”

Section: Resultsmentioning

confidence: 99%

“…>256-fold based on MIC) and bacitracin (ca. 2,000,000-fold based on MBC) [ 15 , 17 ]. Based on MIC and MBC changes, OG has relatively less antimicrobial synergy in S. epidermidis compared to the synergy observed in MRSA.…”

Section: Discussionmentioning

confidence: 99%

“…The results of our permeability assay demonstrate that OG permeabilizes the bacterial cell wall in MRSA and S. epidermidis ( Figure 2 ), which may partly explain why OG is synergistic in combination with the antibiotics targeting the bacterial cell wall. In S. epidermidis , OG was not synergistic with antibiotics other than bacitracin and penicillin, whereas OG also generates synergy with antibiotics of other classes, such as gentamicin, tetracycline, and erythromycin in MRSA [ 15 , 17 ]. This indicates that the mechanisms of antimicrobial synergy by OG other than the cell wall permeabilization can be different between these two pathogenic species.…”

Section: Discussionmentioning

confidence: 99%

“…The changes in cell wall permeability by OG were examined according to a previous study with slight modifications [ 17 ]. Briefly, overnight cultures of S. epidermidis and MRSA were washed with PBS and diluted to the OD at 600 nm of 0.5.…”

Section: Methodsmentioning

confidence: 99%

“…Our previous studies demonstrated that octyl gallate (OG) enhanced the antimicrobial and antibiofilm activities of bacitracin, a polypeptide antibiotic widely used in topical antibiotic ointments to treat skin infections [ 13 , 14 ], against methicillin-resistant Staphylococcus aureus (MRSA) [ 15 , 16 ]. Moreover, OG is capable of sensitizing MRSA to β-lactams [ 17 ]. OG is an antioxidant used as a food additive to prevent lipid oxidation of high-fat food [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

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Synergistic Potentiation of Antimicrobial and Antibiofilm Activities of Penicillin and Bacitracin by Octyl Gallate, a Food-Grade Antioxidant, in Staphylococcus epidermidis

Santativongchai

Tulayakul

et al. 2022

Antibiotics

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Staphylococcus epidermidis is a major nosocomial pathogen that frequently forms biofilms on indwelling medical devices. This study aimed to investigate the synergistic antimicrobial and antibiofilm activities of octyl gallate (OG) in combination with penicillin and bacitracin against S. epidermidis. Antimicrobial synergy was assessed by conducting checkerboard titration assays, and antibiofilm activity was determined with biofilm assays and fluorescence microscopy analysis. The presence of 8 µg/mL of OG increased both the bacteriostatic and bactericidal activities of penicillin and bacitracin against S. epidermidis. It lowered the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of penicillin by eight-fold and those of bacitracin by four-fold. Moreover, when used with penicillin or bacitracin, OG significantly decreased the level of biofilm production by preventing microcolony formation. Furthermore, OG significantly permeabilized the bacterial cell wall, which may explain its antimicrobial synergy with penicillin and bacitracin. Together, these results demonstrate that OG, a food-grade antioxidant, can be potentially used as a drug potentiator to enhance the antimicrobial and antibiofilm activities of penicillin and bacitracin against S. epidermidis.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Synergistic Potentiation of Antimicrobial and Antibiofilm Activities of Penicillin and Bacitracin by Octyl Gallate, a Food-Grade Antioxidant, in Staphylococcus epidermidis

Santativongchai

Tulayakul

et al. 2022

Antibiotics

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β-Lactam potentiators to re-sensitize resistant pathogens: Discovery, development, clinical use and the way forward

et al. 2023

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β-lactam antibiotics are one of the most widely used and diverse classes of antimicrobial agents for treating both Gram-negative and Gram-positive bacterial infections. The β-lactam antibiotics, which include penicillins, cephalosporins, monobactams and carbapenems, exert their antibacterial activity by inhibiting the bacterial cell wall synthesis and have a global positive impact in treating serious bacterial infections. Today, β-lactam antibiotics are the most frequently prescribed antimicrobial across the globe. However, due to the widespread use and misapplication of β-lactam antibiotics in fields such as human medicine and animal agriculture, resistance to this superlative drug class has emerged in the majority of clinically important bacterial pathogens. This heightened antibiotic resistance prompted researchers to explore novel strategies to restore the activity of β-lactam antibiotics, which led to the discovery of β-lactamase inhibitors (BLIs) and other β-lactam potentiators. Although there are several successful β-lactam-β-lactamase inhibitor combinations in use, the emergence of novel resistance mechanisms and variants of β-lactamases have put the quest of new β-lactam potentiators beyond precedence. This review summarizes the success stories of β-lactamase inhibitors in use, prospective β-lactam potentiators in various phases of clinical trials and the different strategies used to identify novel β-lactam potentiators. Furthermore, this review discusses the various challenges in taking these β-lactam potentiators from bench to bedside and expounds other mechanisms that could be investigated to reduce the global antimicrobial resistance (AMR) burden.

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Alkyl gallates inhibit serine O-acetyltransferase in bacteria and enhance susceptibility of drug-resistant Gram-negative bacteria to antibiotics

Toyomoto,

Ono,

Shiba

et al. 2023

Front. Microbiol.

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A principal concept in developing antibacterial agents with selective toxicity is blocking metabolic pathways that are critical for bacterial growth but that mammalian cells lack. Serine O-acetyltransferase (CysE) is an enzyme in many bacteria that catalyzes the first step in l-cysteine biosynthesis by transferring an acetyl group from acetyl coenzyme A (acetyl-CoA) to l-serine to form O-acetylserine. Because mammalian cells lack this l-cysteine biosynthesis pathway, developing an inhibitor of CysE has been thought to be a way to establish a new class of antibacterial agents. Here, we demonstrated that alkyl gallates such as octyl gallate (OGA) could act as potent CysE inhibitors in vitro and in bacteria. Mass spectrometry analyses indicated that OGA treatment markedly reduced intrabacterial levels of l-cysteine and its metabolites including glutathione and glutathione persulfide in Escherichia coli to a level similar to that found in E. coli lacking the cysE gene. Consistent with the reduction of those antioxidant molecules in bacteria, E. coli became vulnerable to hydrogen peroxide-mediated bacterial killing in the presence of OGA. More important, OGA treatment intensified susceptibilities of metallo-β-lactamase-expressing Gram-negative bacteria (E. coli and Klebsiella pneumoniae) to carbapenem. Structural analyses showed that alkyl gallate bound to the binding site for acetyl-CoA that limits access of acetyl-CoA to the active site. Our data thus suggest that CysE inhibitors may be used to treat infectious diseases caused by drug-resistant Gram-negative bacteria not only via direct antibacterial activity but also by enhancing therapeutic potentials of existing antibiotics.

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Potentiation of β-Lactams against Methicillin-Resistant Staphylococcus aureus (MRSA) Using Octyl Gallate, a Food-Grade Antioxidant

Cited by 7 publications

References 25 publications

Synergistic Potentiation of Antimicrobial and Antibiofilm Activities of Penicillin and Bacitracin by Octyl Gallate, a Food-Grade Antioxidant, in Staphylococcus epidermidis

Synergistic Potentiation of Antimicrobial and Antibiofilm Activities of Penicillin and Bacitracin by Octyl Gallate, a Food-Grade Antioxidant, in Staphylococcus epidermidis

β-Lactam potentiators to re-sensitize resistant pathogens: Discovery, development, clinical use and the way forward

Alkyl gallates inhibit serine O-acetyltransferase in bacteria and enhance susceptibility of drug-resistant Gram-negative bacteria to antibiotics

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