When pathogenic bacteria first enter your body, they are vastly outnumbered. If your immune system catches them too early, it’s game over for the bacteria. So how do bacteria survive long enough to make you sick? They lay low and wait for the right moment to strike – focusing on multiplying within the body instead of producing virulence factors (illness causing weapons and immune-fighting tools). When there are enough bacterial cells in an area the cells will attack together, suddenly expressing the virulence factors that cause your body to become sick.
Now you might be wondering how single-celled organisms like bacteria can coordinate an attack on their host. After all, it’s not like they can call each other up on the phone to make plans for their Tuesday night attack on your immune system. Fortunately for them, evolution has equipped them with a different sort of communication system: quorum sensing. Quorum sensing is used for all sorts of bacterial parties, from producing gorgeous light shows to the formation of biofilms. Several variations of quorum systems have evolved within the bacterial domain, but they all follow the same basic principles: Individual bacterial cells produce signals, called autoinducers, which either passively diffuse or are secreted into the area around them. As more and more bacterial cells amass in the environment, there are more and more autoinducers present. When the density of the signal molecules hits a certain threshold, all the bacterial cells responding to that signal begin to modify their gene expression, or which genes they are using, in order to take collective action.
Figure 1: Scanning Electron Microscopy (SEM) images of Brucella abortus growing in a biofilm. Panel A is at 1,500x magnification and Panel B is at 4,000x magnification. Images from Tang et al. 2019.
One microbe that does this is Brucella abortus, a gram-negative bacterium, that has a small, rod-like shape. It causes brucellosis, a disease which causes abortion in cattle and other animals like elk or bison. It can spill over and infect humans, but unless you work closely with cattle or drink unpasteurized (“raw”) milk or dairy products, you’re unlikely to get it. Those unfortunate enough to be infected experience flu-like systems and can develop serious chronic conditions, such as arthritis and endocarditis. B. abortus’s quorum system is an AHL LuxI-LuxR type system unique to gram-negative bacteria. What does that jumble of acronyms mean? Well, it describes the three main parts of the system: what produces the signal, the signal itself, and what responds to the signal. LuxI proteins produce AHL signal molecules, which bind to LuxR proteins, causing changes in the cell’s gene expression. The groups of proteins and signals are named after the first LuxI-LuxR system described, which was that of Aliivibrio fischeri (referenced above).
Figure 2. The lifecycle of B. abortus in animals from Moreno 2014.
B. abortus has a less well studied system, where not all the players and pathways are known. For example, while some AHL signals have been identified, the LuxI proteins that make them haven’t been. There are at least two LuxR proteins, VjbR and BabR, that play a role in activating virulence factors, but their roles are still unclear.
Caudill et al., 2025, looked at quorum sensing in B. abortus. They infected mice with a few different strains: one without VjbR, one without BabR, one without both VjbR and BabR, and a wild-type strain, and then tested how long the bacteria lived within the mice sustaining an infection. They found that compared to the wild type strain and the strains with only a single protein, the strain without the VjbR and BabR proteins was not able to sustain an infection. They also found that the bacteria with a single protein was able to sustain an infection. Figure 2 shows the results of this experiment, specifically comparing the amount of colony-forming units in the spleen of the mice they infected. The first part of the figure (A) shows that the strain without both proteins (∆vjbR ∆babR) was not able to grow and maintain an infection. The second part of the figure (B) shows the difference in the number of colony-forming units of the bacteria 1 and 3 days post-infection, but did not find any significant results. The last part (C) showed that 10 and 21 days post-infection, the strains without the proteins grew significantly worse than the wild-type strain.
Figure 3. Differences in strains of bacteria with or without various proteins. 2308 corresponds to the wild type strain, ∆vjbR ∆babR corresponds to strains without either protein, ∆vjbR corresponds to strains without the VjbR protein, and ∆babR corresponds to strains without BabR. This figure shows that ∆vjbR ∆babR is not able to sustain an infection (A), there are no significant differences in the number of colony-forming units from one to three days (B), and that the growth of strains without one or both proteins was significantly less after 21 days of infection than the wild-type strain (C).
The researchers also looked at whether the expression of these proteins was more regulated by the receiving signal or by transcription.They performed RNA sequencing on each strain, which allowed them to see what genes were expressed by the cells in each condition. They found that the presence of VjbR and/or BabR had more effect on the genes expressed by the bacterium than the presence of the AHL signals that the proteins were responding to. When examining the different strains, they interestingly found that ∆vjbR ∆babR (the strain without either protein) still started responding to the quorum-sensing signal despite the lack of protein regulators. In particular, the important transcriptional changes are the activation of flagellar genes, which allow for Brucella to move around, and the secretion of virulence factors. VjbR and BabR are critical in producing these rather than the AHL signal in quorum sensing. Lastly, they found that deleting the VjbR and BabR proteins changed other LuxR protein receptors, leading to other virulence factors to be released.
Overall, this is one of the first looks into how B. abortus uses LuxR proteins and quorum sensing to control virulence and evade our immune systems’ best effortsBased on all the tests they ran and RNA-sequencing, they figured out that BabR is able to maintain normal function of the cell even without VjbR, but cannot maintain an infection. On the other hand, VjbR is sufficient on its own to maintain an infection to a chronic state– In other words VjbR is a major player in getting cows (and people!) sick with brucellosis, while BabR plays a more minor role. Based on this, we think it could be interesting to look at VjbR as a target for antibiotics in treating brucellosis. We’re excited to see where research into B. abortus goes next!
About the Authors:
Tessa Lancaster ‘25 and Sander Ivanenko ‘25 are seniors in the Biology department of Mount Holyoke College. Sander currently does research on injury biomechanics and they hope to pursue physical therapy and rehabilitation research post-graduation. Tessa is an Environmental Studies/Biology double major and post-graduation, she will be pursuing her PhD in soil microbiology and nutrient cycling at the University of New Hampshire. Outside of Microbiology class, this duo loves to spend time outside and with their little creatures (several cats and a dog!).
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