- A substance made by yeast in the probiotic drink kefir inhibits pathogenic bacteria, including Vibrio cholerae and Salmonella enterica.
- The substance, called tryptophol acetate, works by disrupting communication among the bacteria.
- The discovery could inspire the development of new ways to tackle antibiotic resistant bacteria.
People may have been producing and drinking kefir, a fermented milk drink that originated in Tibet and the North Caucasus, for thousands of years.
People can make the sour, slightly effervescent brew by infusing milk with kefir grains, which are a starchy matrix containing a symbiotic community of lactic acid bacteria, acetic bacteria, and yeasts.
The drink has many reputed health benefits, which include lowering cholesterol, reducing inflammation, and exerting an antioxidant effect.
In common with other probiotics, kefir also has antimicrobial properties. However, scientists were unsure exactly how it inhibits the growth of disease-causing bacteria.
Researchers at Ben-Gurion University of the Negev (BGU) in Be’er Sheva, Israel, have now discovered that a type of yeast in kefir called Kluyveromyces marxianus secretes a molecule that disrupts bacterial communication.
Scientists already knew that plants and algae produce this substance, called tryptophol acetate, but this is the first time that they have found a yeast that makes it.
They discovered that tryptophol acetate interferes with “quorum sensing” — a form of microbial communication — in several disease-causing bacteria.
In quorum sensing, bacteria release signaling molecules into their surroundings. When the molecules reach a particular concentration, they trigger changes in the expression of genes in bacteria of the same species.
These changes allow disease-causing bacteria to coordinate their activity according to their numbers. This coordination is necessary for some bacteria to defend themselves or attack their hosts.
In some cases, when they reach a certain density, the microbes may come together to form a slimy, protective coating, or “biofilm,” on a surface.
In lab cultures, the researchers found that tryptophol acetate had an inhibitory effect over quorum sensing in several disease-causing bacteria, including some Gram-negative bacteria.
Some of the tested species were:
- Pseudomonas aeruginosa, which causes pneumonia when it infects the lungs.
- S. enterica, which is responsible for food poisoning.
- Staphylococcus aureus, which can trigger sepsis, among other life threatening infections.
- V. cholerae, which causes cholera.
The research, which Ph.D. student Orit Malka led, appears in the journal BMC Microbiome.
“These results are notable, since this is the first demonstration that virulence of human pathogenic bacteria can be mitigated by molecules secreted in probiotic milk products, such as yogurt or kefir,” says senior author Prof. Raz Jelinek.
The scientists focused in particular on the effect of tryptophol acetate on V. cholerae.
They found that the substance blocked quorum sensing in this bacteria and reduced its virulence.
It did this by changing the expression of bacterial genes that control quorum sensing.
The researchers write that this kind of interference in bacterial communication may be commonplace in complex environments where many different microorganisms live together, such as in probiotic food or the human gut.
The development of antibiotic resistance in bacteria poses a major threat to public health.
In recent years, scientists have begun to explore alternatives to conventional antibiotics, including drugs that interfere with quorum sensing.
The researchers behind the latest discovery have set up a company to develop and market tryptophol acetate and other small molecules through BGN Technologies, which is BGU’s technology transfer organization.
“In a world where antibiotic resistant bacteria are becoming an imminent threat, the novel molecules discovered by BGU scientists pave a completely new path for fighting bacterial infections by disrupting cell-cell communications in pathogenic bacteria.”
– Josh Peleg, CEO of BGN Technologies.
In a follow-up study, which they have not yet published, the researchers discovered that the same molecules might have anti-inflammatory properties.
According to the scientists, their work in animal models of disease hints that the molecules could calm the excessive immune response known as the cytokine storm that has occurred in some people with severe COVID-19.