A new study indicates that a glowing, ocean-dwelling microbe found inside an adorable species of squid could be the key to uncovering novel antibiotic treatments in an age of increasing antibiotic resistance.
Meet Aliivibrio fischeri (formerly known as Vibrio fischeri before a recent genus change), an adaptable marine microbe that lives freely in our oceans and contributes to the survival of multiple marine species through symbiosis. A. fischeri is capable of bioluminescence making it a popular friend choice in the deep, dark waters of the ocean. Famously, the Hawaiian Bobtail Squid found off the coasts of the Hawaiian Islands, forms a symbiotic relationship with A. fischeri. The microbe lives happily inside the squid's “light organ” making the organ glow while the squid hunts at night, hiding its shadow from the ocean floor and allowing it to sneak up on its prey.
This bioluminescent ability is possible through quorum sensing, a form of bacterial communication in which millions of individual cells can work together as one organism. Imagine thousands of fans jumping up and down together at a concert, connected by the music even without all seeing or hearing each other. Quorum sensing works in a similar way, with millions of microbes being able to sense those around them and coordinate to share one focus or goal. This ability to enter a sort of “hive mind” requires the release of and response to specific signaling factors that scientists have identified and studied extensively.
While A. fischeri was the first microbe discovered to do this quorum sensing communication, it turns out that many different kinds of bacteria do this, including pathogenic ones that use quorum sensing to launch attacks on the human body. Quorum sensing is how pathogenic bacteria plot and execute invasions of the immune system and adapt to and overcome our bodies’ built in defense mechanisms.
Current medications used to fight bacterial infections involve killing the bacteria or preventing them from growing and dividing. But a pattern of antibiotic resistance has emerged, with many infections persisting despite the use of these medications that used to work so well.
In a new study out of Budapest University, Éva Fenyvesi and colleagues are investigating ways to stop quorum sensing by creating drugs that bind to signaling factors after they are released and prevent them from being received and responded to by other bacteria. These satisfyingly named “quorum quenchers” would be a novel approach to stopping the spread of bacterial infections and could help solve the ongoing issue of antibiotic resistance.
You might be wondering how this works. The important things to know about these new drugs are that they are cyclodextrins (abbreviated to CDs) and they trap signal molecules thereby stopping quorum sensing. Think back to the concert analogy and imagine the music suddenly cutting out. With no steady beat to jump up and down to, the concertgoers are no longer connected to each other across the large stadium and are left standing around confused as to where the music went.
After developing a variety of CDs, it was time to see which drugs could effectively turn off the music. In order to test these quorum quenchers, scientists turned to our friend A. fischeri. This is a great model organism for these experiments as we can know visually whether or not quorum sensing is occurring based on the amount of bioluminescence we see. If quorum sensing is working, we will see happy, glowing A. fischeri. If quorum sensing is not working (due to the quorum quenchers) then A. fischeri will glow less or not glow at all.
Figure 6 shows the quantification of these experiments through a measure of “bioluminescent inhibition.” The % bioluminescent inhibition is calculated by a fancy piece of equipment called a fluorometer that measures how much light is emitted by the glowing bacteria. This then allows us to calculate how much they are NOT glowing, or how much the bioluminescent activity is being inhibited by the quorum quenchers. Additionally, the bacteria are being exposed to various amounts of the drugs (0.008 mM, 0.04 mM, 0.2 mM, or 1 mM) for various lengths of time (30, 60 or 90 minutes).
We can see that multiple of these drugs, especially those used in panels B and D, induce significant bioluminescent inhibition, meaning they are effectively preventing quorum sensing. However, there is a lot of variation in the effectiveness of dose and exposure timing in the CDs used in panels B and D, showing that there is more to be learned about these drugs. This data poses questions about how dosage and exposure timing could be perfected to result in the most inhibition. Future studies could turn to animal models to answer these questions and test these new quorum quenchers against pathogenic bacteria.
Overall, this study presents A. fischeri as a model organism for studying quorum sensing and introduces us to a potential new form of antibiotics: quorum quenchers. These drugs take a completely new approach to stopping bacterial virulence and could ultimately help improve public health across the globe.
Aliivibrio fischeri is crucial to the success of these experiments and to our understanding of quorum sensing. Figure 7 shows some historical moments in the life of A. fischeri and without needing to understand every step on the timeline, we can see that this microbe has made big steps in our understanding of bacteria and of the world around us. This recent discovery of quorum quenchers adds another significant event to the list and hopefully helps us feel grateful for one of the smaller things we share the planet with.
Meet Aliivibrio fischeri (formerly known as Vibrio fischeri before a recent genus change), an adaptable marine microbe that lives freely in our oceans and contributes to the survival of multiple marine species through symbiosis. A. fischeri is capable of bioluminescence making it a popular friend choice in the deep, dark waters of the ocean. Famously, the Hawaiian Bobtail Squid found off the coasts of the Hawaiian Islands, forms a symbiotic relationship with A. fischeri. The microbe lives happily inside the squid's “light organ” making the organ glow while the squid hunts at night, hiding its shadow from the ocean floor and allowing it to sneak up on its prey.
Figure 1. Image of hawaiian bobtail squid with size reference. Source: Margaret McFall-Ngai - Divining the Essence of Symbiosis: Insights from the Squid-Vibrio Model
This bioluminescent ability is possible through quorum sensing, a form of bacterial communication in which millions of individual cells can work together as one organism. Imagine thousands of fans jumping up and down together at a concert, connected by the music even without all seeing or hearing each other. Quorum sensing works in a similar way, with millions of microbes being able to sense those around them and coordinate to share one focus or goal. This ability to enter a sort of “hive mind” requires the release of and response to specific signaling factors that scientists have identified and studied extensively.
Figure 2. Luminescent A. fischeri in culture. Source: (Septer & Visick, 2024)
Figure 3. Image from a stadium concert. Source: Mo Mulready
While A. fischeri was the first microbe discovered to do this quorum sensing communication, it turns out that many different kinds of bacteria do this, including pathogenic ones that use quorum sensing to launch attacks on the human body. Quorum sensing is how pathogenic bacteria plot and execute invasions of the immune system and adapt to and overcome our bodies’ built in defense mechanisms.
Current medications used to fight bacterial infections involve killing the bacteria or preventing them from growing and dividing. But a pattern of antibiotic resistance has emerged, with many infections persisting despite the use of these medications that used to work so well.
In a new study out of Budapest University, Éva Fenyvesi and colleagues are investigating ways to stop quorum sensing by creating drugs that bind to signaling factors after they are released and prevent them from being received and responded to by other bacteria. These satisfyingly named “quorum quenchers” would be a novel approach to stopping the spread of bacterial infections and could help solve the ongoing issue of antibiotic resistance.
You might be wondering how this works. The important things to know about these new drugs are that they are cyclodextrins (abbreviated to CDs) and they trap signal molecules thereby stopping quorum sensing. Think back to the concert analogy and imagine the music suddenly cutting out. With no steady beat to jump up and down to, the concertgoers are no longer connected to each other across the large stadium and are left standing around confused as to where the music went.
Figure 5. Visual of a small molecule being trapped by a larger one. Source: Lorenzo Fortunato at researchgate.net
After developing a variety of CDs, it was time to see which drugs could effectively turn off the music. In order to test these quorum quenchers, scientists turned to our friend A. fischeri. This is a great model organism for these experiments as we can know visually whether or not quorum sensing is occurring based on the amount of bioluminescence we see. If quorum sensing is working, we will see happy, glowing A. fischeri. If quorum sensing is not working (due to the quorum quenchers) then A. fischeri will glow less or not glow at all.
Figure 6. Bioluminescence inhibition of A. fischeri based on the dose of and time exposed to various quorum quenchers. Source: (Fenyvesi et al. 2024)
Figure 6 shows the quantification of these experiments through a measure of “bioluminescent inhibition.” The % bioluminescent inhibition is calculated by a fancy piece of equipment called a fluorometer that measures how much light is emitted by the glowing bacteria. This then allows us to calculate how much they are NOT glowing, or how much the bioluminescent activity is being inhibited by the quorum quenchers. Additionally, the bacteria are being exposed to various amounts of the drugs (0.008 mM, 0.04 mM, 0.2 mM, or 1 mM) for various lengths of time (30, 60 or 90 minutes).
We can see that multiple of these drugs, especially those used in panels B and D, induce significant bioluminescent inhibition, meaning they are effectively preventing quorum sensing. However, there is a lot of variation in the effectiveness of dose and exposure timing in the CDs used in panels B and D, showing that there is more to be learned about these drugs. This data poses questions about how dosage and exposure timing could be perfected to result in the most inhibition. Future studies could turn to animal models to answer these questions and test these new quorum quenchers against pathogenic bacteria.
Overall, this study presents A. fischeri as a model organism for studying quorum sensing and introduces us to a potential new form of antibiotics: quorum quenchers. These drugs take a completely new approach to stopping bacterial virulence and could ultimately help improve public health across the globe.
Figure 7. Timeline of significant discoveries about A. fischeri. Source: (Septer & Visick, 2024)
Aliivibrio fischeri is crucial to the success of these experiments and to our understanding of quorum sensing. Figure 7 shows some historical moments in the life of A. fischeri and without needing to understand every step on the timeline, we can see that this microbe has made big steps in our understanding of bacteria and of the world around us. This recent discovery of quorum quenchers adds another significant event to the list and hopefully helps us feel grateful for one of the smaller things we share the planet with.
About the Author:
Mo Mulready ‘25 is a neuroscience major from Kingston, New York. She loves music and loves singing in the Mount Holyoke College Chorale! After graduation, she is moving to Boston to work as a Clinical Research Coordinator at Dana-Farber Cancer Institute.
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