Antibiotics were a huge advance for the field of medicine because they decreased the risk of people getting sick due to harmful bacteria. However, bacteria quickly learned to “fight back” against these powerful medicines. Antibiotic-resistant bacteria, increasingly frequent nowadays, cannot be killed by antibiotics, making infections with these organisms very dangerous. Some common infections have become extremely difficult or even impossible to cure, leading to an alarming public health problem. In this article, we will discuss how helpful “predator bacteria” might be useful in fighting antibiotic-resistant infections. The bacterium we chose to study is called Bdellovibrio bacteriovorus, it lives in the healthy human gut and is capable of preying on other bacteria. In the future, might this bacterium be an effective treatment for dangerous bacterial infections? We think so!
Fighting bacteria… And How Bacteria Fought Back!
Up until about 80 years ago, around the time when your grandparents were kids, antibiotics were not available to treat bacterial infections. This meant that if a child got even a small wound while playing outdoors, for example, bacteria could get into the wound and cause a dangerous infection that could potentially lead to the child’s death. Lucky for us, in 1928, a famous scientist discovered the first powerful antibiotic—penicillin—which could kill bacteria and cure infections. Penicillin virtually eliminated the risk of getting sick from bacterial infections for a little while. But unfortunately, in just a few years, bacteria managed to develop strategies to “fight back” against penicillin, so that this antibiotic was no longer as effective. Scientists responded by creating new types of antibiotics, but the bacteria fought back against those, too. This is the worrying phenomenon known as antibiotic resistance. Today, many antibiotics no longer work on certain types of bacteria, and infections with these antibiotic-resistant bacteria have become scary again! (to learn more about antibiotic resistance, see this Frontiers for Young Minds article).
Keeping Balance In Ecosystems: The Predation Phenomenon
How can this serious problem of antibiotic resistance be solved? Scientists are studying various strategies, and one involves something called natural predation. In any ecosystem, a group of living things coexist in harmony, interacting with each other within a specific environment. For example, in a forest ecosystem, wolves, foxes, deer, rabbits, birds, insects, oak trees, beech trees, bushes, and grass all form the living parts of the ecosystem. Imagine what would happen if, for example, all the predators (wolves and foxes) disappeared. The prey (deer and rabbits) would increase in number and would soon eat all the grass, bushes, and tree leaves until they eventually destroyed their own ecosystem—ultimately endangering their own existence.
Predators are not “bad guys”—they are actually nature’s superheroes—, due to their important job of keeping ecosystems in balance. By keeping the populations of prey organisms in check, predators make sure prey animals do not destroy the ecosystem due to their out-of-control growth, so that all the plants and animals can continue to live together in a balanced and healthy way. So, predators are ecological balancers, keeping all the species in the correct proportions and preventing some species from overpopulating and destroying the harmony needed to keep an ecosystem functioning.
But ecosystems do not only exist in forests—there are ecosystems in and on our bodies, too!— One example is the gut microbiota. The gut microbiota is a team of billions and billions of microorganisms living in harmony inside our guts. These little guys help us to digest our food and they make important vitamins, strengthen the natural defenses of our bodies, prevent us from getting sick, and generally help us to feel good.
We have therefore seen that ecological balance occurs when different species coexist in the right proportions in order to maintain a healthy and functional environment and that predators play a very important role in all of this. Everything works well when all the various members of the gut ecosystem get along and live together peacefully. However, if the balance among them gets messed up, like when one type of bacteria becomes too bossy and tries to take over, it creates disharmony or, in other words, an imbalance that can harm our health. But here is the cool part: just like there are helpful predators in a forest, there are also predator bacteria in our intestines that make sure that ecosystem stays balanced and healthy. Among these bacterial superheroes present in our intestines, the most famous is called Bdellovibrio bacteriovorus.
Bdello: Helpful Predator Bacteria
Bdellovibrio bacteriovorus (called Bdello for short) was identified by two scientists during the late 1960s, at Indiana University (USA). Their work laid the foundation for understanding Bdello’s unique predatory behavior and how they might be used to control harmful bacteria.
Bdello is much smaller than other types of bacteria, but it is a very fast moving bacterium, capable of destroying bigger bacteria—including those harmful to our health—. Bdello lives in both terrestrial (land-based) and aquatic (water-based) environments . Bdello attack other bacteria (their prey) by invading them and replicating (reproducing) once they are inside. Bdello then returns to the environment by destroying their prey . The main prey hunted by Bdello are certain bacterial species (belonging to the group of Gram-negative bacteria) that are frequently associated with human infections . The ability of Bdello to prey upon dangerous types of bacteria (Figure 1) led scientists to wonder whether they could be used to treat infections caused by antibiotic-resistant bacteria .
Bacteria Fighting Bacteria To Keep Us Healthy?
First, we wanted to see whether Bdello was healthy or harmful to the human body. We found that Bdello is always present in the intestines of healthy people . Interestingly, in patients affected by several diseases (such as Celiac Disease and Inflammatory bowel disease) Bdello was heavily reduced. So, Bdello is not harmful to human health. Furthermore, we observed that Bdello is important because it controls the overgrowth of its bacterial prey, keeping harmony within the natural microbial populations living in our intestines. Therefore, this bacterium is very beneficial for the wellbeing of the human body.
Next, we wanted to know whether Bdello could be used to fight infections caused by antibiotic-resistant bacteria (Figure 2). We evaluated the predatory activity of Bdello against some antibiotic- resistant bacteria that often cause human infections, such as Pseudomonas aeruginosa and a disease-causing strain of Escherichia coli—both difficult to cure with antibiotics [6, 7]. Our results, conducted in vitro (in test tubes) also confirmed in vivo (using a living grater moth larva)  indicate that Bdello may prey on both the harmful to humans bacteria P. aeruginosa and Escherichia coli reducing their growth. These encouraging experimental results, obtained in our laboratory, give rise to hope that one day the same good results can also be obtained directly on human patients suffering from infections with antibiotic-resistant bacteria, obviously, more experiments will be needed before we can get to this.
Bdello Vs. Antibiotic Resistance: Mother Nature Gives Us A Hand?
So far, our research has taught us that the tiny bacterium Bdello seem to be a natural part of the ecosystem of the healthy human intestines, and that this predatory bacterium is essential to maintain the healthy balance of the others bacteria within the intestinal ecosystem. Our work using simple in vitro and in vivo experimental models, so far indicates that Bdello’s natural predatory activity could be used to treat worrying infections with antibiotic-resistant bacteria that cannot be effectively treated with antibiotics. Who knows, maybe in the near future we will be using Bdello to treat infections, instead of using ineffective antibiotics! This would help to reduce the dangerous health problems all over the world caused by dangerous infections with antibiotic-resistant bacteria. Who knows, maybe Mother Nature will give us a hand once again!
Antibiotics: ↑ Drugs capable of killing dangerous disease-causing bacteria.
Antibiotic Resistance: ↑ The very widespread phenomenon nowadays, through which many bacteria have managed to develop various strategies to resist the antibiotic drugs.
Natural Predation: ↑ When a predator hunts and eats other animals overgrowing in the same environment, it helps keep this ecosystem naturally balanced and healthy.
Ecosystem: ↑ the set of all living organisms, their relationships and the environment in which they live all together.
Predator: ↑ An animal that hunts and kills other animals for food.
Gut Microbiota: ↑ A community of various species of microorganisms living in harmony inside our gut playing a big role in helping us digest food and stay healthy.
In Vitro and In Vivo: ↑ Scientific expressions of Latin origin which refers respectively to experiments conducted in test tubes (in vitro) or on live animals (in vivo): what happens in vitro does not always also happen in vivo.
Conflict of Interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
 ↑ Stolp, H., and Starr, M. P. 1963. Bdellovibrio bacteriovorus gen. et sp. n., a predatory, ectoparasitic, and bacteriolytic microorganism. Antonie Van Leeuwenhoek 29:217–48. doi: 10.1007/BF02046064
 ↑ Sockett, R. E. 2009. Predatory lifestyle of Bdellovibrio bacteriovorus. Annu. Rev. Microbiol. 63:523–39. doi: 10.1146/annurev.micro.091208.073346
 ↑ Kadouri, D., and O'Toole, G. A. 2005. Susceptibility of biofilms to Bdellovibrio bacteriovorus attack. Appl. Environ. Microbiol. 71:4044–51. doi: 10.1128/AEM.71.7.4044-4051.2005
 ↑ Negus, D., Moore, C., Baker, M., Raghunathan, D., Tyson, J., Sockett, R. E., et al. 2017. Predator versus pathogen: how does predatory Bdellovibrio bacteriovorus interface with the challenges of killing gram-negative pathogens in a host setting? Annu. Rev. Microbiol. 71:441–57. doi: 10.1146/annurev-micro-090816-093618
 ↑ Iebba, V., Santangelo, F., Totino, V., Nicoletti, M., Gagliardi, A., De Biase, R. V., et al. 2013. Higher prevalence and abundance of Bdellovibrio bacteriovorus in the human gut of healthy subjects. PLoS ONE 8:e0061608. doi: 10.1371/annotation/b08ddcc9-dfdb-4fc1-b2ac-5a4af3051a91
 ↑ Iebba, V., Totino, V., Santangelo, F., Gagliardi, A., Ciotoli, L., Virga, A., et al. 2014. Bdellovibrio bacteriovorus directly attacks Pseudomonas aeruginosa and Staphylococcus aureus Cystic fibrosis isolates. Front. Microbiol. 5:280. doi: 10.3389/fmicb.2014.00280
 ↑ Bonfiglio, G., Neroni, B., Radocchia, G., Pompilio, A., Mura, F., Trancassini, M., et al. 2019. Growth control of adherent-invasive Escherichia coli (AIEC) by the predator bacteria Bdellovibrio bacteriovorus: a new therapeutic approach for Crohn’s disease patients. Microorganisms 8:17. doi: 10.3390/microorganisms8010017