The Effects of Allicin, a Reactive Sulfur Species from Garlic, on a Selection of Mammalian Cell Lines

Gruhlke, Martin C. H.; Nicco, Carole; Batteux, Frédéric; Slusarenko, Alan

doi:10.3390/antiox6010001

Cited by 84 publications

(75 citation statements)

References 59 publications

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“…In the MTT assay, impaired mitochondrial reductase function in otherwise healthy cells will yield falsely low viability results . These factors may lead to discordant results between YO‐PRO and MTT assays …”

Section: Discussionmentioning

confidence: 99%

“…53 These factors may lead to discordant results between YO-PRO and MTT assays. 55 We used cytotoxicity of SMX-HA at 800 lM for statistical comparisons of LTA results, since this metabolite concentration highlighted most of the variability among individuals. However, we did not detect increased cytotoxicity in HS patients compared to TOL patients at this concentration for either method, which was a concern given the results of previous studies.…”

Section: Discussionmentioning

confidence: 99%

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RNA expression profiling in sulfamethoxazole‐treated patients with a range of in vitro lymphocyte cytotoxicity phenotypes

Reinhart

Rose

Panyard

et al. 2018

Pharmacology Res & Perspec

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The lymphocyte toxicity assay (LTA) is a proposed surrogate marker of sulfonamide antibiotic hypersensitivity. In the LTA, peripheral blood mononuclear cells (PBMCs) undergo apoptosis more readily in hypersensitive versus tolerant patients when exposed to drug‐hydroxylamine metabolites in vitro. The purpose of this study was to identify key gene transcripts associated with increased cytotoxicity from sulfamethoxazole‐hydroxylamine in human PBMCs in the LTA. The LTA was performed on PBMCs of 10 patients hypersensitive to trimethoprim‐sulfamethoxazole (HS) and 10 drug‐tolerant controls (TOL), using two cytotoxicity assays: YO‐PRO (n = 20) and MTT (n = 12). mRNA expression profiles of PBMCs, enriched for CD8+ T cells, were compared between HS and TOL patients. Transcript expression was interrogated for correlation with % cytotoxicity from YO‐PRO and MTT assays. Correlated transcripts of interest were validated by qPCR. LTA results were not significantly different between HS and TOL patients, and no transcripts were found to be differentially expressed between the two groups. 96 transcripts were correlated with cytotoxicity by YO‐PRO (r = ±.63‐.75, FDR 0.188). Transcripts were selected for validation based on mechanistic plausibility and three were significantly over‐expressed by qPCR in high cytotoxicity patients: multi‐specific organic anion transporter C (ABCC5), mitoferrin‐1 (SLC25A37), and Porimin (TMEM123). These data identify novel transcripts that could contribute to sulfonamide‐hydroxylamine induced cytotoxicity. These include SLC25A37, encoding a mitochondrial iron transporter, ABCC5, encoding an arylamine drug transporter, and TMEM123, encoding a transmembrane protein that mediates cell death.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

RNA expression profiling in sulfamethoxazole‐treated patients with a range of in vitro lymphocyte cytotoxicity phenotypes

Reinhart

Rose

Panyard

et al. 2018

Pharmacology Res & Perspec

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“…This demonstrates how contingent explorations of natural product antimicrobials are on material preparation and testing conditions. This result is also interesting because allicin can be toxic in high concentrations (61). Reducing the amount of allicin present but maintaining full activity against bacterial biofilms might have been key to producing a safe topical treatment.…”

Section: Discussionmentioning

confidence: 94%

Anti-biofilm efficacy of a medieval treatment for bacterial infection requires the combination of multiple ingredients

Furner-Pardoe

Anonye

Cain

et al. 2020

Preprint

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Novel antimicrobials are urgently needed to combat the increasing occurrence of drug-resistant bacteria and to overcome the inherent difficulties in treating biofilm-associated infections. Research into natural antimicrobials could provide candidates to fill the antibiotic discovery gap, and the study of plants and other natural materials used in historical infection remedies may enable further discoveries of natural products with useful antimicrobial activity. We previously reconstructed a 1,000-year-old remedy containing onion, garlic, wine, and bile salts, which is known as ‘Bald’s eyesalve’, and showed it to have promising antibacterial activity. In this paper, we have found this remedy has bactericidal activity against a range of Gram-negative and Gram-positive wound pathogens in planktonic culture and, crucially, that this activity is maintained against Acinetobacter baumannii, Stenotrophomonas maltophilia, Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus pyogenes in a model of soft-tissue wound biofilm. While the presence of garlic in the mixture is sufficient to explain activity against planktonic cultures, garlic alone has no activity against biofilms. We have found the potent anti-biofilm activity of Bald’s eyesalve cannot be attributed to a single ingredient and requires the combination of all ingredients to achieve full activity. Our work highlights the need to explore not only single compounds but also mixtures of natural products for treating biofilm infections. These results also underline the importance of working with biofilm models when exploring natural products for the anti-biofilm pipeline.ImportanceBacteria can live in two ways, as individual planktonic cells or as a multicellular biofilm. Biofilm helps protect bacteria from antibiotics and makes them much harder to treat. Both the biofilm lifestyle and the evolution of antibiotic resistance mean we urgently need new drugs to treat infections. Here, we show that a medieval remedy made from onion, garlic, wine, and bile can kill a range of problematic bacteria grown both planktonically and as biofilms. A single component of the remedy – allicin, derived from garlic – is sufficient to kill planktonic bacteria. However, garlic or allicin alone do nothing against bacteria when they form a biofilm. All four ingredients are needed to fully kill bacterial biofilm communities, hinting that these ingredients work together to kill the bacteria. This suggests that future discovery of antibiotics from natural products could be enhanced by studying combinations of ingredients, rather than single plants or compounds.

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“…The development of allicin as an antibiotic for clinical use is not completely straightforward, as although it can be easily synthesized (4), is not stable in solution for long periods of time unless it is frozen (33). Moreover, allicin is also inhibitory to mammalian cell growth in a dose-dependent manner (11,34). Furthermore, tissue burns from the inappropriate use of garlic preparations in attempts to treat various conditions have been well documented (2).…”

Section: Discussionmentioning

confidence: 99%

Investigation of the deposition behaviour and antibacterial effectivity of allicin aerosols and vapour using a lung model

et al. 2019

Self Cite

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Allicin is a natural antibiotic produced by garlic as a defence against pathogens and pests. Due to the worldwide increase in antibiotic resistance, new antibiotics are desperately required. Allicin is such a candidate and is active against several multidrug-resistant (MDR) strains of human pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). When administered orally, allicin is titrated out by glutathione in the cells and blood, and effective therapeutic concentrations are difficult to achieve at the site of an infection. However, in the case of lung infections, allicin can be delivered directly to pathogens via the pulmonary route. In this study, we designed and constructed an in vitro lung test rig, which allowed us to model accurately the exposure of lung air-passage surfaces to allicin and gentamicin, in order to examine the feasibility of combating lung infections by direct inhalation. A prototype test rig of lung bronchi with three bifurcations was constructed, which could be coated internally with a thin layer of bacteria-seeded agar medium. The deposition of antimicrobial aerosols on the modelled bronchial surfaces was followed in preliminary tests without the need for animal experiments. The differential sensitivity of the test bacteria to different antibiotics and the dose-dependency of inhibition was shown using the model. Furthermore, a synergistic effect of allicin vapour and ethanol in inhibiting bacterial growth was demonstrated. The modelling of the axial velocity air-flow distribution correlated with the regions indicating the inhibition of bacterial growth, demonstrating that the model has predictive value and can reduce the requirement for animal sacrifice in pre-clinical trials of novel antibiotics.

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The Effects of Allicin, a Reactive Sulfur Species from Garlic, on a Selection of Mammalian Cell Lines

Cited by 84 publications

References 59 publications

RNA expression profiling in sulfamethoxazole‐treated patients with a range of in vitro lymphocyte cytotoxicity phenotypes

RNA expression profiling in sulfamethoxazole‐treated patients with a range of in vitro lymphocyte cytotoxicity phenotypes

Anti-biofilm efficacy of a medieval treatment for bacterial infection requires the combination of multiple ingredients

Investigation of the deposition behaviour and antibacterial effectivity of allicin aerosols and vapour using a lung model

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