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Disrupting Bacterial Communication to Stop Infections



In so many aspects of life, communication is key. We, humans, communicate with each other primarily through language. Bacteria are ubiquitous around us and communicate with each other as well but through a special process called ‘quorum sensing’ [1]. ‘Quorum sensing’ is a truly fascinating process in the bacterial kingdom that scientists and physicians are just beginning to understand. Very recently, two American scientists, Drs. Michael Silverman and Bonnie Bassler, won the 2021 Paul Ehrlich and Ludwig Darmstaedter Prize for elucidating this captivating process that has a huge impact on animal and human health. Bonnie Bassler is Professor at Princeton University and a Howard Hughes Medical Institute Investigator, NJ, while Michael Silverman is Emeritus Professor of the Agouron Institute in La Jolla, CA. Paul Ehrlich was a Noble Prize-winning German Jewish physician and scientist who made significant contributions in the fields of hematology, immunology, and antimicrobial chemotherapy. The Paul Ehrlich and Ludwig Darmstaedter Prize honors scientists who have made significant contributions in Paul Ehrlich's field of research. The Prize has been awarded annually since 1952.


What Is Quorum Sensing?

Quorum sensing describes the ability to detect bacterial cell population density and respond accordingly using gene regulation [1]. In particular, bacteria use signal molecules to gather intelligence about the neighborhood they are in, such as how many other bacteria and what species of bacteria there are present around them. They use this information to decide if or how to engage in collective activities [1].


Dr. Michael Silverman was the first scientist to discover a quorum-sensing circuit in a bioluminescent bacterium called Vibriofischeri in the 1980s [2]. He was able to pinpoint the genes and proteins involved in the production and detection of extracellular signal molecules, which in turn promote the collective behavior of blue-green bioluminescence production [2]. Such behavior is not unique to V. fischeri; in fact, thousands of bacterial species possess similar mechanisms implemented by almost identical genes to those in V. fischeri, allowing them to engage in group behaviors[1].


Highlights:


1. Bacteria can communicate with each other and with viruses and human cells using quorum sensing

2. Quorum sensing can contribute to antibiotic resistance and virulence

3. Pets are impacted by pathogens capable of quorum sensing

4. Novel anti-microbial strategies can be devised by targeting the process of quorum sensing



Bacteria Can Speak Multiple “Languages”

Subsequently in the 1990s, Dr. Bonnie Bassler discovered that bacteria communicated with each other using multiple chemical signal molecules, effectively making them “multi-lingual” [1]. One such example is the autoinducer-2 molecule that enables cross-species communication, which bacteria use to differentiate themselves from other species [1]. Such sophisticated communication mechanisms, previously thought to be exclusive to higher organisms, have in fact been in existence in the bacterial kingdom for billions of years [1]. Later on, Bassler further demonstrated that quorum sensing exists even beyond kingdom boundaries as viruses and host cells, for example, human cells, also engage in such communication [3, 4].


In addition, Bassler, among several researchers, also discovered that quorum sensing plays a key role in pathogen virulence; they demonstrated in animal models that an anti-quorum sensing strategy can effectively halt infection of bacterial pathogens [5]. Moreover, quorum sensing also aids in the process of antibiotic resistance by regulating efflux pumps, which extrude drug molecules out of bacterial cells, or by coordinating the formation of bacterial biofilms, structures of bacterial cells attaching to each other, and a self-produced matrix which cause reduced permeability of drug molecules [6].





The discoveries of Drs. Michael Silverman and Bonnie Bassler are of significant importance in the medical field, including veterinary medicine. As aforementioned, quorum sensing plays a pivotal role in the virulence of disease-causing bacteria and in antibiotic resistance. In pathogenic bacteria such as Staphylococcusaureus and Pseudomonasaeruginosa, which are frequently diagnosed in dogs and other animals by the MiDOG Test, quorum sensing controls many traits including the expression of virulence factors, molecules produced by bacteria in order to aid its colonization of the host, evasion, and suppression of host immune system, entry and exit of host cells, and acquisition of nutrients from host cells [5].


This allows for novel anti-microbial treatment strategies to be developed by focusing on disrupting cell-to-cell communication and in turn halting infection rather than eradicating the bacteria using conventional antibiotics [5]. Such novel treatment options are urgently needed since multi-drug antimicrobial resistance is on the rise in both human and veterinary medicine. You can now aid in this effort and better diagnose bacterial infection in your pet by using our MiDOG Test to find out if your pet’s illness is caused by a bacterial species capable of quorum sensing.






References

1. Miller, Melissa B., and Bonnie L. Bassler. "Quorum sensing in bacteria." Annual Reviews in Microbiology 55, no. 1 (2001): 165-199.

2. Dunlap, Paul V. "Quorum regulation of luminescence in Vibrio fischeri." Journal of molecular microbiology and biotechnology 1, no. 1 (1999): 5-12.

3. Duddy, Olivia P., and Bonnie L. Bassler. "Quorum sensing across bacterial and viral domains." Plos Pathogens 17, no. 1 (2021): e1009074.

4. Holm, Angelika, and Elena Vikström. "Quorum sensing communication between bacteria and human cells: signals, targets, and functions." Frontiers in plant science 5 (2014): 309.

5. Rutherford, Steven T., and Bonnie L. Bassler. "Bacterial quorum sensing: its role in virulence and possibilities for its control." Cold Spring Harbor perspectives in medicine 2, no. 11 (2012): a012427.

6. Zhao, Xihong, Zixuan Yu, and Tian Ding. "Quorum-sensing regulation of antimicrobial resistance in bacteria." Microorganisms 8, no. 3 (2020): 425.

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