Sticky Situations In A Microscopic World

We have all seen photographs or drawings of bacteria. Since the earliest drawings of these microorganisms, over 300 years ago, they have often been shown as small, individually arranged cells of various shapes. However, many species of bacteria are not solitary microorganisms and instead stick together to live in groups called aggregates. The most common type of aggregates are called biofilms, which are mixtures of microorganisms attached to interfaces (for example solid-liquid, liquid-oil, and air-liquid surfaces) and can contain tens to hundreds of bacterial species [1]. Examples of biofilms include dental plaque, the slime on the hulls of ships, and scum that forms on stagnant ponds.

The ability of bacteria to aggregate together is instrumental for biofilms to form. Some bacteria of the same species aggregate together through a process called autoaggregation, and this can help include more of the same species into developing biofilms. Interestingly, microbiologists have also realized that many bacterial species bind to other species through a highly specific process called coaggregation (Figure 1) [2]. Coaggregation might help biofilms form by allowing bacterial species to recognize and specifically stick to other species of bacteria that are already in developing biofilms [2]. Studies have shown that coaggregation mostly happens due to interactions between sticky proteins called adhesins present on the cell surface of a bacterial species and complex sugars called receptors located on the cell surface of another species (Figure 2). Adhesins and receptors are specific—they will only bind to each other if both are the right type. The interaction is a bit like a hand fitting into a glove, but a foot would not fit. Furthermore, bacteria can produce combinations of adhesins and receptors that allow for multiple species to coaggregate with each other and form a network of coaggregated cells. These coaggregation networks have been mapped for many bacteria in human dental plaque (Figure 3) (a type of biofilm that forms on the surface of teeth) and evidence suggests that these networks serve various functions [2]. Coaggregation networks are also being identified in many other environments. These include biofilms in drinking water, on human skin, and even on dogs’ teeth. Coaggregation has been identified in so many environments that it may be a universal phenomenon among bacteria, making it important to understand why and how bacteria do it.

Bringing Bacteria With Different Abilities Together

When thinking about why bacteria coaggregate, one of the most obvious reasons is summed up in the title of a well-regarded paper that focuses on coaggregation between dental bacteria: “Coaggregation: Adhere today, here tomorrow” [3]. Coaggregation helps bacteria to become part of biofilms, which stick tightly to surfaces and are not easily washed away. Other reasons for coaggregation involve the ABCs—alliances, battles, and conspiracies. In the case of alliances, coaggregation can benefit both of the species involved. For example, the oral bacteria Veillonella atypica and Streptococcus gordonii coaggregate. V. atypica needs lactic acid to grow and S. gordonii produces it as a waste material. By coaggregating with S. gordonii, V. atypica can remove the waste material (which benefits S. gordonii) and use it for its own growth [4]. In terms of battles, coaggregation may allow one species to recognize and bind to another species to kill it! This may be the case for the bacterium Lacticaseibacillus rhamnosus, which lives in the human gut and coaggregates with Escherichia coli to kill it [5]. Finally, regarding conspiracies, coaggregation may allow bacteria to swap DNA, the genetic material required for building their cells. This may help the coaggregated bacteria gain new abilities, such as becoming resistant to an antibiotic [2].

Why Study Coaggregation?

Biofilms are a huge problem in healthcare and can also damage homes, factories, and ships. For example, dental plaque forms on teeth and can cause cavities (and visits to the dentist). Biofilms inside pipes corrode their surfaces and can make the water look and taste bad, while biofilms on ship hulls cause damage and slow them down. Coaggregation may help biofilms to form and make them resistant to removal (e.g., with a scrubbing brush). It may also protect the bacteria from being killed by chemical treatments (e.g., with antimicrobial soap).

Preventing coaggregation may stop biofilms from forming as quickly and may make them easier to remove. For example, if we can exhaustively map coaggregation networks in biofilms, we might be able to identify a bacterial species that coaggregates with many other species and target that species to prevent alliances and conspiracies from developing. It may also be possible to use coaggregation to introduce species into biofilms to our advantage. For example, scientists are trying to find out if certain coaggregating probiotic (helpful) bacteria can help change how dental plaque develops, and possibly prevent tooth decay [6]. This kind of biological engineering could reduce our dependence on chemical treatments and antibiotics. Ultimately, if we understand how and why bacteria coaggregate, we can figure out how to select for coaggregating bacterial communities that will benefit our health and support a healthy environment.

Conclusions

Through coaggregation, bacteria can stick to other bacterial species and, once in a coaggregate, new behaviors and abilities emerge. Studying one species on its own will not necessarily reveal how it will behave in a biofilm that contains many species with which it can coaggregate. Alliances, battles, and conspiracies may be only some of the interactions that are happening in biofilms. There could be bacterial deception where, for example, one species coaggregates with another and tricks it into making a special nutrient. There could even be bacterial corruption, where coaggregation causes one or more species to damage other bacterial species, the host, or the environment. Ultimately, if we can manipulate coaggregation, we might be able to change which bacterial species are in a biofilm, how the individual species interact with the host or the environment, or the properties and activities of the entire biofilm community. Such manipulation could help us to treat disease or environmental problems caused by bacteria—from preventing cavities to protecting the hulls of ships.

Glossary

Biofilms: ↑ A collection of bacteria that are stuck to an interface and each other.

Autoaggregation: ↑ The aggregation of bacterial cells of the same species.

Coaggregation: ↑ The specific recognition and attachment of different species of bacteria to one another.

Adhesin: ↑ A protein on the surface of a bacterial cell that specifically recognizes and binds to a receptor on another bacterial cell.

Receptor: ↑ A molecule containing complex sugars on the surface of a bacterial cell that is recognized by an adhesin.

Coaggregation Networks: ↑ Coaggregates of more than two different species that are linked together through specific interactions.

Probiotic: ↑ Bacteria that can improve health by interacting with other bacteria.

Host: ↑ A large organism (e.g., person) that is colonized by and shelters microorganisms.

Acknowledgments

This work was supported by NIH grant R01 DE025225.

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.