Researchers at The Hebrew University of Jerusalem have found an unlikely ally in the fight against antibiotic resistant infections.

Since the discovery of Penicillin, humanity has been locked in an arms race with pathogenic bacteria. For decades, scientists have developed new drugs in an attempt to gain the upper hand against these invaders but the tenacious pathogens always seem to find a way to develop resistances to humanity’s latest and greatest weapons in this biological war. Now, researchers have discovered previously unknown effects of anandamide, an endocannabinoid, on multi-drug resistant Staphylococcus aureus that may shift the advantage back into humanity’s favor. According to the study authors, anandamide was able to sensitize MDRSA and MRSA to common antibiotics such as methicillin through a variety of mechanisms.

One way pathogens can gain resistance to common antibiotics is through efflux pumps which allow the bacteria to move the drugs from the interior of the cell to the exterior. If the antibiotics are pumped out fast enough, the bacterial cell can survive and reproduce leading to continued infection. According to the researchers, anandamide effectively inhibited the action of efflux pumps leading to a higher concentration of the drugs within the bacterial cells.

Another method of resistance is biofilm formation. When bacteria conglomerates as a biofilm, the bacterial cells are actually nestled into a protective layer of polysaccharides called exopolysaccharides which the bacterial cells secrete. This layer helps protect the bacteria from the antibiotic medications and allows them to cluster together. The study authors claim that anadamide prevents or inhibits the secretion of exopolysaccharides, removing another layer of antibiotic resistance.

Most antibiotics kill bacteria by inhibiting their ability to form an effective cell membrane. The bacteria essentially bleed to death as the goo inside them seeps out. Researchers found that bacteria treated with anandamide showed several changes in the cell membrane including structural changes and decreased ATPase activity. Many cellular processes rely on energy from ATP. Of note, the researches found that anandamide interfered with cell division in a way that halted it during daughter cell separation leading to a much reduced rate of reproduction.

All these effects, taken together, lead to a dramatic sensitization of MDRSA and MRSA to common antibiotics, which is great news for humans because it could buy us time to find the next generation of antibiotics for a world in which drug resistance seems to expand at a faster rate than new drug discoveries.

You can read the original paper here

1 – Sionov, R.V.; Banerjee, S.; Bogomolov, S.; Smoum, R.; Mechoulam, R.; Steinberg, D. Targeting the Achilles’ Heel of Multidrug-Resistant Staphylococcus aureus by the Endocannabinoid Anandamide. Int. J. Mol. Sci. 2022, 23, 7798. https://doi.org/10.3390/ijms23147798

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