Bacteria. Can’t live with them. Can’t live without them. Commensal bacteria keep us healthy; they provide essential nutrients, defend against colonization of pathogens, are the building blocks of the gastrointestinal tract, and stimulate the immune system when needed. However, pathogenic bacteria can cause a plethora of issues and diseases that can wreak havoc on our bodies and, in some cases, result in reduced quality of life and death.
Before the invention of antibiotics, death from a pathogenic bacterium was much more common, something the post-antibiotic world often forgets. With the rise in antibiotic-resistant bacterium, the concern has been reignited among health care professionals.
However, what if other mechanisms could control bacteria? Well, I’m here to tell you it is possible, through the perturbation of quorum sensing.
What is Quorum Sensing?
If you can imagine a social network for bacteria, that is essentially what quorum sensing is; it is how bacteria communicate. Bacteria use quorum sensing to communicate with members of their own species as well as members of other species. They communicate through chemicals called autoinducers.1
The importance of this regarding oral health is that this system controls biofilm formation and virulence. At low cell density, the autoinducers stay at low concentrations that prevent detection. Over time, the autoinducers become more abundant and activate gene transcription, activity, and gene expression.2
Quorum sensing plays a role in biofilm formation. Pathogenic bacteria cannot form biofilm without a critical number of bacteria cells. Quorum sensing “organizes” the “party” of bacteria that becomes the biofilm we all work so hard to overcome.
If you can imagine, one tiny bacteria cell cannot overwhelm a healthy immune system. Therefore, they fly under the radar until they have become diverse and more populous, at which time they form biofilm.
This is all done through quorum sensing. Quorum sensing then plays a role in virulence that signals the inflammatory response and the cascade of events that lead to periodontal disease and/or dental caries. Dental professionals despise oral biofilm, but the real offender is the “event organizer,” quorum sensing.3 Without the organization that quorum sensing provides, biofilm would be unable to form and would not be able to turn up the virulence factor. This makes it a very appealing target for the management of biofilm and disease onset and progression.
Manipulating Quorum Sensing to Prevent Disease
The overuse and abuse of antibiotics have caused concern in the medical and dental communities regarding antibiotic-resistant bacteria. Perturbation of quorum sensing may be the tool we need to overcome these resistant bacteria.
Studies testing current pharmaceuticals’ ability to perturb quorum sensing have been published with promising findings. In one study, the authors utilized febuxostat (brand name: Uloric, an antihyperuricemic agent used to treat gout4) to inhibit growth, biofilm formation, and virulence, among other microbial activities of Pseudomonas aeruginosa (a bacteria responsible for urinary tract, respiratory tract, and wound/burn infections). The authors found febuxostat showed growth inhibitory effects, reduced biofilm formation, significant decreases in expression of quorum sensing genes, and diminished virulence through reduced expression of a key virulence factor produced by Pseudomonas aeruginosa.
These findings are promising as more studies evaluate other FDA-approved drugs and their ability to perturb quorum sensing in different bacterial strains.5
As promising as this is, finding the right medicament to use in quorum sensing perturbation is a delicate process because our beneficial commensal bacteria use this same communication system to establish their communities. Destruction of beneficial commensal bacteria is not the goal and could lead to other oral health and systemic health concerns, such as fungal overgrowth.
Quorum Sensing and Periodontal Disease
Quorum sensing perturbation in pathogenic periodontal pathogens is still in the early research phase. However, some progress has been made in targeting pathogenic periodontal bacteria. Mechanisms explored include enzymatic degradation of signaling molecules, blocking signal generation, and blocking signal reception.
The use of plant-based molecules may be more reasonable for oral health. Products based on plants, algae, and fungi that produce molecules that inhibit quorum sensing in bacteria rather than a systemic pharmaceutical may be more appealing to patients, considering it will be one less pill to take and won’t rely on patient compliance. In addition, it will likely be more effective for site-specific periodontal infection.
Plant, algae, and fungi that produce quorum sensing inhibition abilities include:7
- Sponge Agelas oroides
- Red marine algae
- Grapefruit extract
- Sweet basil
- Clove extract (eugenol)
- Clove extract (hexane and methanol)
- Piper nigrum, Piper betle, and Gnetum gnemon
Though it may seem tempting, the above list is not meant to be arbitrarily recommended to patients. We need more research to confirm the mechanism of action before we can make bold claims about these naturally occurring substances’ ability to prevent or slow the progression of periodontal disease. However, it is something to keep in mind as new studies are conducted, and new products are produced that may target quorum sensing in the prevention and progression of periodontal disease.
Though we have successful treatment for periodontal disease and are well versed in principles of preventing it, having more tools in our armamentarium would be nice, especially if it were in the form of a dental product that prevents colonization, biofilm formation, and virulence of periodontal pathogens. It is unclear how these products will be distributed (prescription versus OTC), and there is no certainty they will come to fruition as more research is necessary before a product can be manufactured for use.
This may be a future prospect as more research is certainly needed to try to narrow down options and target specific bacteria, preventing damage to beneficial commensal bacteria while eliminating pathogenic bacteria. However, it doesn’t seem unreasonable to be optimistic about the prospect. Quorum sensing perturbation could change the need for antibiotic treatment for other bacterial infections as well, helping the dental and medical community overcome the serious issue of antibiotic-resistant bacteria.
Keep your ears and eyes open for future published literature and possible new products that may come to market with the claim of “quenching quorum sensing” to prevent biofilm and bacterial infections.
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- Windsor, W.J. (2020, June 12). How Quorum Sensing Works. American Society for Microbiology. https://asm.org/Articles/2020/June/How-Quorum-Sensing-Works
- Rutherford, S.T., Bassler, B L. Bacterial quorum sensing: its role in virulence and possibilities for its control. Cold Spring Harbor Perspectives in Medicine. 2012: 2(11): a012427. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3543102/
- Bachtiar, Boy Muchlis. Quorum Sensing and its Role in Oral Biofilms Development. Journal of Dentistry Indonesia. 2006; 13(1). https://www.researchgate.net/publication/307779979_QUORUM_SENSING_AND_ITS_ROLE_IN_ORAL_BIOFILMS_DEVELOPMENT
- Drugs.com. n.d. Febuxostat. Retrieved from https://www.drugs.com/mtm/febuxostat.html
- Abbas, H., Soliman, W., Shaldam, M. Perturbation of Quorum Sensing in Pseudomonas aeruginosa by Febuxostat. Advances in Microbiology. 2018; 8: 650-664. https://www.scirp.org/journal/paperinformation.aspx?paperid=87037
- Plančak, D., Musić, L., Puhar, I. Quorum Sensing of Periodontal Pathogens. Acta Stomatologica Croatica. 2015; 49(3): 234-241. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4993591/
- Basavaraju, M., Sisnity, V.S., Palaparthy, R., Addanki, P.K. (2016). Quorum quenching: Signal jamming in dental plaque biofilms. Journal of Dental Sciences. 2016; 11(4): 349-352. https://doi.org/10.1016/j.jds.2016.02.002