Exploring Plant-Based Acid to Combat Antibiotic Resistance

Jim Crocker
14th May, 2024

Exploring Plant-Based Acid to Combat Antibiotic Resistance

Image Source: Natural Science News, 2024

Key Findings

  • Researchers at King Saud University found that gallic acid from pomegranate can boost tetracycline's effect on resistant bacteria
  • Gallic acid was shown to inhibit bacterial efflux pumps, which are used by bacteria to resist antibiotics
  • The study suggests gallic acid could help revive the use of older antibiotics against drug-resistant infections
In recent years, the medical community has faced a growing challenge: antibiotic resistance. Bacteria, like Staphylococcus aureus, have developed mechanisms to evade the effects of antibiotics, rendering many traditional treatments ineffective. This has led scientists to explore alternative strategies to combat bacterial infections. One promising avenue is the use of natural compounds found in plants that can inhibit bacterial efflux pumps, a common resistance mechanism. Efflux pumps are transport proteins that bacteria use to expel toxic substances, including antibiotics, from their cells. By inhibiting these pumps, it may be possible to restore the effectiveness of antibiotics against resistant strains of bacteria. A recent study by researchers at King Saud University has shed light on a potential breakthrough in this area[1]. The study focuses on gallic acid, a compound extracted from pomegranate molasses. Gallic acid is known for its antibacterial properties, and the researchers sought to determine its effectiveness as an efflux pump inhibitor (EPI) against S. aureus, particularly strains resistant to tetracycline. Tetracycline is a broad-spectrum antibiotic that has been widely used since its discovery in the 1940s[2]. However, resistance to tetracycline has become increasingly common due to the spread of resistant genes and mutations that alter bacterial cell permeability or protect ribosomes from the drug's action[2]. The researchers combined gallic acid with tetracycline and observed a significant decrease in the minimum inhibitory concentration (MIC) necessary to inhibit bacterial growth. This suggests that gallic acid enhances the antibiotic's effectiveness. Additionally, when S. aureus was grown on agar plates containing ethidium bromide, a substance typically expelled by efflux pumps, there was reduced bacterial growth and fluorescence. This indicates that gallic acid was indeed inhibiting the efflux pumps, preventing the bacteria from removing the ethidium bromide. To understand how gallic acid interacts with the bacterial efflux pumps at a molecular level, the team employed molecular docking analyses. These computer simulations predict how small molecules, like gallic acid, bind to proteins, such as the tet family efflux pumps responsible for tetracycline resistance. The results showed a promising affinity, meaning that gallic acid could potentially bind well to these pumps and block their function. However, the study found no direct relationship between the presence of certain efflux pump genes (tetK and Qac A/B) and the action of gallic acid. This suggests that the compound's inhibitory effects may not be due to direct interaction with these genes. The exact mechanism by which gallic acid reverses resistance remains to be fully understood. The findings of this study are in line with previous research that has demonstrated the potential of plant-derived compounds to inhibit bacterial efflux pumps. For instance, a methanolic extract of pomegranate was previously shown to enhance the effectiveness of ciprofloxacin against certain resistant Gram-negative bacteria[3]. Similarly, quercetin, another plant compound, was found to inhibit efflux pumps in S. aureus[4]. These studies, along with the current research, highlight the potential of natural products as adjunct therapies to combat antibiotic resistance. The rise of multidrug-resistant bacteria is a pressing health concern, with multidrug efflux pumps playing a central role in the development of these formidable pathogens[5]. The work being done at King Saud University is part of a broader effort to understand and combat this issue. By identifying natural compounds like gallic acid that can inhibit efflux pumps, scientists are working toward new solutions that could revitalize old antibiotics and offer hope in the fight against resistant infections. In summary, the study from King Saud University provides promising evidence that gallic acid could be used as an efflux pump inhibitor to restore the efficacy of tetracycline against resistant strains of S. aureus. While more research is needed to fully understand the mechanisms involved and to develop practical treatments, this study represents an important step forward in the ongoing battle against antibiotic-resistant bacteria.

MedicineBiotechBiochem

References

Main Study

1) Evaluation of phyto-gallic acid as a potential inhibitor of Staphylococcus aureus efflux pump mediated tetracycline resistance: an in-vitro and in-silico study.

Published 11th May, 2024

https://doi.org/10.1080/14786419.2024.2349810

Related Studies

2) Tetracycline antibiotics: mode of action, applications, molecular biology, and epidemiology of bacterial resistance.

Journal: Microbiology and molecular biology reviews : MMBR, Issue: Vol 65, Issue 2, Jun 2001

3) Pomegranate pericarp extract enhances the antibacterial activity of ciprofloxacin against extended-spectrum β-lactamase (ESBL) and metallo-β-lactamase (MBL) producing Gram-negative bacilli.

https://doi.org/10.1016/j.fct.2012.09.001

4) Enhancement of the antibiotic activity by quercetin against Staphylococcus aureus efflux pumps.

https://doi.org/10.1007/s10863-021-09886-4

5) Multidrug Efflux Pumps in Staphylococcus aureus: an Update.

https://doi.org/10.2174/1874285801307010059


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