Quorum Sensing: Friend or Foe
By Jivin Yalamanchili, Northville High School, Northville, Michigan, USA
A man screams; hints of gradient black strike with a speed nothing short of instantaneous. The most revered killer in Africa, the black mamba, has just cut his life down to 7 hours in the blink of an eye. How could a creature so small defeat a much larger human? The story exemplifies the truisms presented by the tale of “David and Goliath.” In both scenarios, the aggressor did not show even hints of danger, but rather secretly crept until the blow would be swift and decisive. Similarly, the fact that small bacteria continually conquer much larger organisms often eludes common thought. As a matter of fact, pathogens killed 75% of people in 2012, which led researchers at Princeton University to wonder how something so small can overpower something so large and evolved (CDC, 2012). Bonnie Bassler, a Howard Hughes Medical Institute Investigator and Squibb professor at Princeton, discovered that bacteria have mass modes of communication that allow them to precisely coordinate biological attacks. She then coined the term Quorum Sensing for this phenomenon and continued research into its potential applications (NSF.gov, 2011). Through extensive testing, Bassler not only discovered the inner workings of bacterial communication, but also uncovered fathomable cures whose future intertwined with that of Quorum Sensing.
Quorum Sensing allows microscopic bacteria to beat massive organisms by exemplifying the cliche platitude “strength in numbers." Quorum Sensing occurs in only single-celled bacteria (from what we know) and relies on a tally system. Every cell, whether a bacteria cell or not, has a cell membrane littered with receptors. These receptors are enzymes that have a specific shape that matches to a ligand (a signaling molecule); when attached, the ligand initiates transduction, which begins a response (see Figure 1). All bacteria have two types of cellular communication: intra-cellular and inter-cellular. Intra-cellular communication tells the bacteria how many of each other there are in an organism, which allows them to make informed decisions (Bassler, 2013). When their numbers reach a considerable amount, the bacteria all simultaneously release their response, allowing for a multitude of effects, ranging from releasing luciferin, a bioluminescence, to administering a fatal toxin. With sufficient numbers, a debilitated prokaryote manifests itself into a virulent mass powerful enough to create a glowing squid or a deadly pathogen capable of killing trillion-celled organisms. To stop miscounts and interceptions of messages, bacteria have evolved and created specific ligands and receptors unique to their own species, allowing for biological encryption (Bassler, 2013). On the other hand, inter-species communication tells bacteria whose species is in the majority and whose is the minority, which allows them to make subsequent decisions. Unlike intra-species communication, all bacteria utilize the same “universal molecule” and a corresponding receptor, allowing them all to communicate between species (Bassler, 2013). By exploiting this mode of communication used by all bacteria, a new wave of medications that disable “the internet” for these bacteria, leaving them completely stranded, can easily result in potential cures.
Figure 1. A diagram showing how Intra-cellular and Inter-cellular communication takes place.
By incorporating the “universal molecule” into new medicines, the new wave of superbugs (bacteria that have developed immunity against medications) that defeated the greatest of doctors and evolved against the newest of medicines can finally become eradicated diseases, plaguing nothing more than archaic pages of history books. The bane of all cures, cancer, effectively utilizes Quorum Sensing to trick the host’s body. To understand how such an event happens, one must understand that cancer develops from a gene mutation, which means that the resulting cancer cell has access to all the host cell’s DNA. With the DNA comes the genes that code specific ligands, which allow normal cells to communicate within the body. By manufacturing certain peptides that signal angiogenesis, the creation of blood cells, cancer cells sustain themselves. In other words, cancerous cells send out ligands that signal angiogenesis to occur, which brings the tumors the nutrients through blood, allowing those growths to reach massive sizes that normally would not have been supported by the body’s original circulatory system (Wynendaele, et al., 2015). Another superbug, Alzheimer’s, utilizes cellular communication similar to a tactic adopted by business moguls known as the bait and switch. The very spirochetes that cause the infection slowly divide, develop, and assess their numbers using intra-specific Quorum Sensing until they have the masses to create a strong biofilm. The biofilm attracts the attention of the immune system, which creates NF-κB: a protein complex that controls gene transcription. NF-κB then makes Aβ (a precursor protein) to destroy the spirochetes. Despite this, the pathogens are protected by the biofilm, and eventually, with continual production of Aβ, cerebral neurocircuitry begins to degrade, bringing forth the distinguishing neuro-impaired characteristics (Allen, et al., 2016). These are only two common examples picked from millions of natural applications, yet they differ almost entirely, which shows the diversity of Quorum Sensing. With this information, few scientists have begun to realize that individual cures no longer can withhold waves of pathogens, which leaves only one effective solution: a universal cure, the bane of superbugs that utilizes the “universal molecule” to undermine the very basis upon which bacterium function (See Figure 2).
Figure 2. The “Universal Molecule” (Bassler, 2013).
Superbugs have plagued 21st century medicine and left researchers to navigate a diverse and ever-changing environment of pathogens. With discoveries of the “Universal Molecule”, the idea of disease or pathogenic bacteria can become extinct. With it, disease ridden third-world countries will flourish, infant mortality will disappear, and global health will prosper. Though these ideas seem extraterrestrial and hyperbolic, the facts show that all pathogenic bacteria use some form of Quorum Sensing to coordinate attacks which means without this communication, they can no longer attack. This form of attack becomes especially relevant to bacterium such as drug-resistant tuberculosis, which has developed immunity to almost every known antibiotic (Ventola, 2015). The common misconception that Quorum Sensing can only hurt humans should no longer halt further research. However, the question arises: will this form of manipulation foster a new wave of superbugs that will become impenetrable to human advancements?
Quorum Sensing, the very thing that allows bacteria to unite, may also become humanity’s greatest weapon against incurable diseases. Through research and experimentation, the “universal molecule” can become the translator, making bacteria pawns of the human race. As a result, diseases will no longer plague the earth, but rather bacteria will allow vast advancements in biotechnological space. The only hurdle remaining is the current view of Quorum Sensing. Once pharmacologists realize that, “if you can’t beat them, join them,” Quorum Sensing will finally be viewed as a friend rather than foe.
Allen, H. (2016, June 27). Alzheimer's disease: Assessing the role Of Spirochetes, biofilms, the immune system, and Amyloid-β with regard to potential treatment and Prevention. Retrieved April 18, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5008232/
Bassler, B. (2013, February 09). How bacteria "TALK" - Bonnie Bassler. Retrieved April 18, 2021, from https://www.youtube.com/watch?v=KXWurAmtf78
C. (2012). CDC National Health Report Highlights. Retrieved April 18, 2021, from https://www.cdc.gov/healthreport/publications/compendium.pdf
Cancer.gov. (2018, April 2). Angiogenesis inhibitors. Retrieved April 18, 2021, from https://www.cancer.gov/about-cancer/treatment/types/immunotherapy/angiogenesis-inhibitors-fact-sheet#:~:text=wet%20macular%20degeneration.-,Why%20is%20angiogenesis%20important%20in%20cancer%3F,chemical%20signals%20that%20stimulate%20angiogenesis
Jiang, Q., Chen, J., Yang, C., Yin, Y., & Yao, K. (2019, April 4). Quorum sensing: A prospective therapeutic target for bacterial diseases. Retrieved April 18, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6475571/
Miller, M. B., & Bassler, B. L. (2001, October). Quorum sensing in bacteria. Retrieved April 18, 2021, from https://www.annualreviews.org/doi/abs/10.1146/annurev.micro.55.1.165
NSF.gov. (2011, October). Bonnie Bassler. Retrieved April 18, 2021, from https://www.nsf.gov/nsb/members/current_members/bassler.jsp#:~:text=Bonnie%20Bassler%20is%20a%20Howard,She%20received%20a%20B.S.&text=The%20research%20in%20her%20laboratory,process%20is%20called%20quorum%20sensing
Ventola C. L. (2015). The antibiotic resistance crisis: part 1: causes and threats. P & T : a peer-reviewed journal for formulary management, 40(4), 277–283. Retrieved May 31, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4378521/#:~:text=Carbapenem%2Dresistant%20Enterobacteriaceae%20(CRE),%E2%80%9D%20against%20drug%2Dresistant%20pathogens.
Wynendaele, E., Verbeke, F., D’Hondt, M., Hendrix, A., Wiele, C., Burvenich, C., Spiegeleer, B. (2015, January 02). Crosstalk between the microbiome and cancer cells by quorum sensing peptides. Retrieved April 18, 2021, from https://www.sciencedirect.com/science/article/abs/pii/S0196978114003520#:~:text=Quorum%20sensing%20peptides%20promote%20cancer,for%20some%20quorum%20sensing%20peptides.https://www.youtube.com/watch?v=KXWurAmtf78