Antioxidant-based synergistic eradication of methicillin-resistant Staphylococcus aureus (MRSA) biofilms with bacitracin

Oh, Euna; Bae, Junghee; Kumar, Ankit; Choi, Hyo-Jick; Jeon, Byeonghwa

doi:10.1016/j.ijantimicag.2018.03.006

Cited by 18 publications

(13 citation statements)

References 14 publications

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“…This finding could be reasonably related to the longer alkyl chain in the chemical structure of octyl gallate, which might explain its better antibiofilm activity. In addition, a recent investigation by Oh et al [26] demonstrated a similar suppressive effect by octyl gallate on the production of biofilm biomass by another gram-positive bacterium— Staphylococcus aureus .…”

Section: Resultsmentioning

confidence: 90%

Suppressive Effects of Octyl Gallate on Streptococcus mutans Biofilm Formation, Acidogenicity, and Gene Expression

et al. 2019

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The accumulation of biofilm by Streptococcus mutans bacteria on hard tooth tissues leads to dental caries, which remains one of the most prevalent oral diseases. Hence, the development of new antibiofilm agents is of critical importance. The current study reports the results from testing the effectiveness of octyl gallate (C8-OG) against: (1) S. mutans biofilm formation on solid surfaces (polystyrene, glass), (2) acidogenicity, (3) and the expression of biofilm-related genes. The amount of biofilm formed by S. mutans bacteria was evaluated using the colorimetric method and optical profilometry. The pH of the biofilm growth medium was measured with microelectrode. A quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to assess the expression of genes encoding glucan binding protein B (gbpB), glucosyltransferases B, -C, -D (gtfB, -C, -D), and the F-ATPase β subunit of the F1 protein (atpD). The results show that C8-OG significantly diminished biofilm formation by exposed S. mutans on solid surfaces and suppressed acidogenicity in a dose-dependent manner, compared to unexposed bacteria (p < 0.05). The C8-OG concentration of 100.24 µM inhibited S. mutans biofilm development on solid surfaces by 100% and prevented a decrease in pH levels by 99%. In addition, the RT-qPCR data demonstrate that the biofilm-producing bacteria treated with C8-OG underwent a significant reduction in gene expression in the case of the four genes under study (gbpB, gtfC, gtfD, and atpD), and there was a slight decrease in expression of the gtfB gene. However, C8-OG treatments did not produce significant expression change compared to the control for the planktonic cells, although there was a significant increase for the atpD gene. Therefore, C8-OG might be a potent antibiofilm and/or anticaries agent for oral formulations that aim to reduce the prevalence of dental caries.

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Section: Resultsmentioning

confidence: 90%

Suppressive Effects of Octyl Gallate on Streptococcus mutans Biofilm Formation, Acidogenicity, and Gene Expression

et al. 2019

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“…BAC interferes with the dephosphorylation of bactoprenol (C 55 -isoprenyl pyrophosphate); a membrane lipid-carrier that transports peptidoglycan-precursors across the membrane for peptidoglycan biosynthesis 23,24 . The use of BAC in combination with other compounds against S. aureus has been studied before such as in combination with colistin 25 and alkyl gallates 26,27 . Colistin is believed to damage the cell membrane thus increasing entry of BAC into the cell or by increasing availability of divalent ions such as Zn 2+ .…”

Section: Discussionmentioning

confidence: 99%

Cannabidiol is an effective helper compound in combination with bacitracin to kill Gram-positive bacteria

Wassmann

Højrup

Klitgaard

2020

Sci Rep

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The cannabinoid cannabidiol (CBD) is characterised in this study as a helper compound against resistant bacteria. CBD potentiates the effect of bacitracin (BAC) against Gram-positive bacteria (Staphylococcus species, Listeria monocytogenes, and Enterococcus faecalis) but appears ineffective against Gramnegative bacteria. CBD reduced the MIC value of BAC by at least 64-fold and the combination yielded an FIC index of 0.5 or below in most Gram-positive bacteria tested. Morphological changes in S. aureus as a result of the combination of CBD and BAC included several septa formations during cell division along with membrane irregularities. Analysis of the muropeptide composition of treated S. aureus indicated no changes in the cell wall composition. However, CBD and BAC treated bacteria did show a decreased rate of autolysis. The bacteria further showed a decreased membrane potential upon treatment with CBD; yet, they did not show any further decrease upon combination treatment. Noticeably, expression of a major cell division regulator gene, ezrA, was reduced twofold upon combination treatment emphasising the impact of the combination on cell division. Based on these observations, the combination of CBD and BAC is suggested to be a putative novel treatment in clinical settings for treatment of infections with antibiotic resistant Gram-positive bacteria. Since the discovery of penicillin in 1928 by Sir Alexander Fleming, antibiotics have saved millions of lives from fatal infections worldwide. However, with time bacteria have developed mechanisms to escape the effects of antibiotics. The amount of antibiotics used seems to be directly related to development of antibiotic resistance. Similarly, a growing number of multi drug resistant (MDR) bacteria is a result of inadequate intentions to solve the resistance problem and increasing unmet demands for new antibacterial drugs 1. With fewer antibiotics available to treat MDR bacterial infections, the possibility of entering a pre-antibiotic era is looming ahead. Alternative strategies are being explored and helper compounds, also known as antibiotic potentiators or resistant breakers, are attracting attention 2. Helper compounds are non-antibiotic compounds functioning as adjuvants for antibiotics to operate in synergy through various mechanisms including efflux pump inhibition, inhibition of enzymes, and changes in membrane permeability, all of which may contribute to increasing the efficacy of a specific antibiotic 3,4. Drugs found to contain helper compound properties are normally used for treatment of non-infectious diseases but may contain some degree of antibacterial activity itself 5. Helper compounds are usually associated with side-of-action in the central and peripheral nervous system as local anaesthetics and in psychopharmaceutic practice, where they usually block membrane associated transporter activity 5. Overuse of antibiotics is the main cause of antibiotic resistance. Therefore, by combining an antibiotic with a helper compound less antibiotic is needed in...

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“…Since our previous studies showed that some gallic acid derivates generated antimicrobial synergy with bacitracin [ 13 , 14 ], in this study, we investigated whether gallic acid derivatives may increase antimicrobial activity in MRSA when used in combination with antibiotics of other classes. The initial screening was conducted by examining the antimicrobial activities of erythromycin, ampicillin, gentamicin, kanamycin, and ciprofloxacin in combination with gallic acid, methyl gallate, ethyl gallate, propyl gallate, butyl gallate, OG, dodecyl gallate, and stearyl gallate.…”

Section: Resultsmentioning

confidence: 99%

“…For instance, clavulanic acid is not antimicrobial but is used with amoxicillin, a β-lactam drug, because clavulanic acid inhibits the function of β-lactamases [ 12 ]. Previously, we demonstrated that the antimicrobial and anti-biofilm activities of bacitracin, an antimicrobial peptide, were synergistically increased in MRSA when combined with octyl gallate (OG), a food additive approved by the U.S Food and Drug Administration (FDA) to prevent lipid oxidation [ 13 , 14 ]. In the present study, we determined antimicrobial synergy between OG and other antibiotic classes and discovered that OG significantly potentiated β-lactams against MRSA.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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Methicillin-resistant Staphylococcus aureus (MRSA) is resistant to a number of antibiotics of clinical importance and is a serious threat to public health. Since bacteria rapidly develop resistance even to newly discovered antibiotics, this study aimed to develop drug potentiators to enhance the antibacterial activity of existing antibiotics for the control of MRSA. Based on our previous studies, screening of antimicrobial synergy was conducted with gallic acid and its derivatives using checkerboard assays. Antimicrobial synergy was confirmed with MRSA isolates from clinical cases. Combinations of penicillin, ampicillin, and cephalothin with octyl gallate (OG), an antioxidant approved by the US Food and Drug Administration (FDA), consistently exhibited synergistic bacteriostatic and bactericidal activities against MRSA, rendering MRSA sensitive to β-lactams. The fractional inhibitory concentration (FIC) and fractional bactericidal concentration (FBC) indices exhibited that the antimicrobial effects of OG were synergistic. The results of a permeability assay showed that OG significantly increased the permeability of the bacterial cell wall. Despite the intrinsic resistance of MRSA to β-lactams, the findings in this study demonstrated that OG enhanced the activity of β-lactams in MRSA and sensitized MRSA to β-lactams, suggesting that OG can be used as a drug potentiator to control MRSA using existing antibiotics.

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Antioxidant-based synergistic eradication of methicillin-resistant Staphylococcus aureus (MRSA) biofilms with bacitracin

Cited by 18 publications

References 14 publications

Suppressive Effects of Octyl Gallate on Streptococcus mutans Biofilm Formation, Acidogenicity, and Gene Expression

Suppressive Effects of Octyl Gallate on Streptococcus mutans Biofilm Formation, Acidogenicity, and Gene Expression

Cannabidiol is an effective helper compound in combination with bacitracin to kill Gram-positive bacteria

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

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