Summary: Epigallocatechin (EGCG), a natural antioxidant found in green tea, may help in the fight against antibiotic-resistant bacteria. EGCG restores the activity of aztreonam, an antibiotic commonly used to treat infections caused by P. aeruginosa. The bacteria is resistant to major classes of antibiotics and is currently treated with a combination of drugs.
Source: University of Surrey
Scientists at the University of Surrey have discovered that a natural antioxidant commonly found in green tea can help eliminate antibiotic-resistant bacteria.
The study, published in the Journal of Medical Microbiology, found that epigallocatechin (EGCG) can restore the activity of aztreonam, an antibiotic commonly used to treat infections caused by the bacterial pathogen Pseudomonas aeruginosa.
P. aeruginosa is associated with serious respiratory tract and bloodstream infections and in recent years has become resistant to many major classes of antibiotics. Currently a combination of antibiotics is used to fight P. aeruginosa.
However, these infections are becoming increasingly difficult to treat, as resistance to last line antibiotics is being observed.
To assess the synergy of EGCG and aztreonam, researchers conducted in vitro tests to analyse how they interacted with the P. aeruginosa, individually and in combination. The Surrey team found that the combination of aztreonam and EGCG was significantly more effective at reducing P. aeruginosa numbers than either agent alone.
This synergistic activity was also confirmed in vivo using Galleria mellonella (Greater Wax Moth larvae), with survival rates being significantly higher in those treated with the combination than those treated with EGCG or aztreonam alone. Furthermore, minimal to no toxicity was observed in human skin cells and in Galleria mellonella larvae.
Researchers believe that in P. aeruginosa, EGCG may facilitate increased uptake of aztreonam by increasing permeability in the bacteria. Another potential mechanism is EGCG’s interference with a biochemical pathway linked to antibiotic susceptibility.
Lead author Dr Jonathan Betts, Senior Research Fellow in the School of Veterinary Medicine at the University of Surrey, said:
“Antimicrobial resistance (AMR) is a serious threat to global public health. Without effective antibiotics, the success of medical treatments will be compromised. We urgently need to develop novel antibiotics in the fight against AMR. Natural products such as EGCG, used in combination with currently licenced antibiotics, may be a way of improving their effectiveness and clinically useful lifespan.”
Professor Roberto La Ragione, Head of the Department of Pathology and Infectious Diseases in the School of Veterinary Medicine at the University of Surrey, said:
“The World Health Organisation has listed antibiotic resistant Pseudomonas aeruginosa as a critical threat to human health. We have shown that we can successfully eliminate such threats with the use of natural products, in combination with antibiotics already in use. Further development of these alternatives to antibiotics may allow them to be used in clinical settings in the future.”
This research was carried out in partnership with Public Health England, the German Centre for Infection Research and the University of Cologne.
University of Surrey
Natasha Meredith – University of Surrey
The image is in the public domain.
Original Research: Open access
“Restoring the activity of the antibiotic aztreonam using the polyphenol epigallocatechin gallate (EGCG) against multidrug-resistant clinical isolates of Pseudomonas aeruginosa”. Jonathan Betts.
Journal of Medical Microbiology doi:10.1099/jmm.0.001060.
Restoring the activity of the antibiotic aztreonam using the polyphenol epigallocatechin gallate (EGCG) against multidrug-resistant clinical isolates of Pseudomonas aeruginosa
Pseudomonas aeruginosa is an important Gram-negative pathogen that is intrinsically multidrug-resistant (MDR) and frequently associated with healthcare-associated outbreaks. With increasing resistance to antibiotics and with very few novel drugs under development, clinicians often use combinations to treat critically ill patients.
The aim of this study was to evaluate the ability of epigallocatechin (EGCG) to restore the activity of aztreonam against clinical MDR strains of P. aeruginosa.
Checkerboard and time–kill kinetic assays were performed to assess synergy in vitro and the Galleria mellonella model of infection was used to test the efficacy of the combination in vivo. Accumulation assays were performed to gain insight into the mechanism of action.
The results demonstrate that synergy between aztreonam and EGCG exists [fractional inhibitory concentration indices (FICIs) 0.02-0.5], with the combination affording significantly (P=<0.05) enhanced bacterial killing, with a >3 log10 reduction in colony-forming units ml−1 at 24 h. EGCG was able to restore susceptibility to aztreonam to a level equal to or below the breakpoint set by the European Committee for Antimicrobial Susceptibility Testing. In G. mellonella, the combination was superior to monotherapy, with increased larval survival observed (94 % vs ≤63 %). We also demonstrated the relatively low toxicity of EGCG to human keratinocytes and G. mellonella larvae. Accumulation assay data suggest that the mechanism of synergy may be due to EGCG increasing the uptake of aztreonam.
EGCG was able to restore the activity of aztreonam against MDR P. aeruginosa . The data presented support further evaluation of the aztreonam–EGCG combination and highlight its potential for use in clinical medicine.