Throughout life, diverse communities of bacteria circulate in the mouth, performing an array of useful tasks. They help break down food particles, inhibit pathogens, produce vitamins and other essential nutrients, regulate pH levels and protect against tooth decay and gum disease.

The dysregulation of oral microbes, however, is linked with a variety of diseases. Harmful bacteria are often shrouded with sticky accumulations that form a biofilm, allowing bacteria to adhere to surfaces and protect themselves from predation. The new study demonstrates that phages — viruses that infect bacteria — can be carried in the wake of helpful microbes, targeting and helping to eliminate the biofilm. Download Full Image

In new research, Abhishek Shrivastava and his colleagues describe the gliding activity of oral bacteria and their ability to transport phages — a class of virus known to infect bacteria — like hitchhikers catching a ride in the bacterial wake.

Shrivastava is a researcher in the Biodesign Center for Fundamental and Applied Microbiomics and an assistant professor in the School of Life Sciences at Arizona State University.

The research appears in the current issue of the journal Microbiology Spectrum.

The study demonstrates how the corkscrew-like gliding motion of oral bacteria provides a delivery system for these highly specific and powerful antibacterial agents. Surfing within the "swarm fluid" produced by beneficial bacteria, phages eventually reach their targets — harmful bacteria that the body seeks to eliminate.

Such harmful bacteria are often protected by biofilms, sticky accumulations that help the bacteria adhere to surfaces and act as a protective fortress. But as the new study shows, the one-two combination of beneficial bacteria and phage viruses can break through these defenses. The helpful bacteria bore tunnels into the biofilm, allowing phage viruses to penetrate and reach deeper layers where harmful bacteria are hiding, infect these bacteria and then destroy them.

“We have identified a promising opportunity through this discovery. By showcasing the ability of gliding bacteria to serve as vehicles for antimicrobials and beneficial viruses, we have established a solid foundation for future application development,” Shrivastava says. “Our next step is to utilize this proof-of-concept to create practical and impactful solutions.”

The research is a significant advance for the field of phage therapy and may help overcome some of the drawbacks associated with conventional antibiotics, including their side effects and the development of antibiotic resistance. The research also sheds new light on the subtle and dynamic interactions taking place within colonies of oral microbes.

Phage therapy, which uses viruses to treat bacterial infections, is commonly used for treating burn wound infections and chronic ear infections. This study has demonstrated improved delivery of topically applied phages within an E. coli biofilm in laboratory settings. The research paves the way for improved delivery of phages for clinical conditions, a potential advance for infection treatment.

Abhishek Shrivastava

Microbial metropolis

The human mouth is home to diverse microbial communities, with over 700 different species of bacteria identified. While the total number of bacteria in the human mouth is difficult to precisely quantify — as it can vary greatly depending on factors such as oral hygiene, diet and overall health — it's estimated to range from hundreds of millions to billions. These vast colonies play a crucial role in oral health and overall wellness.

An imbalance in this community can lead to oral diseases such as caries, gum disease and can potentially contribute to systemic conditions including heart disease and diabetes. Regular oral hygiene practices like tooth brushing, flossing and dental check ups are crucial to maintaining a healthy balance of bacteria in the mouth.

In a series of experiments, the researchers demonstrate that the oral bacterium Capnocytophaga gingivalis forms tunnel-like structures within Escherichia coli biofilms – slimy fortresses that these sometimes-harmful bacteria create to stick to various surfaces and shield themselves from assault.

Once C. gingivalis has successfully infiltrated the E. coli biofilm, phages carried along in the bacterium’s "swarm fluid" are able to penetrate areas within the biofilm that were previously unreachable.

The study suggests that active transportation of phage viruses by the gliding bacterium C. gingivalis is significantly more effective than natural diffusion. During natural diffusion, phage viruses spread out slowly and randomly in all directions, and this process can be inefficient for reaching their target, especially in complex environments such as biofilms.

However, when carried by C. gingivalis, the phages are transported within the fluid flow produced by the bacteria's movement. This method provides the phages a more direct and rapid route to their target, increasing the interaction rate between the phages and the bacteria they prey on.  

Turning viruses into allies

The ability of C. gingivalis to form tunnel-like structures in an E. coli biofilm and deliver phages to previously inaccessible regions of the biofilm lead to a significantly higher rate of disruption in the E. coli colony compared to when phages simply diffuse to it. Indeed, the researchers concluded that phages swept along by C. gingivalis bacteria were roughly 10 times more efficient at disrupting colonies of E. coli and penetrating their biofilm defenses compared with phages that travelled purely by diffusion.

The findings highlight the importance of physical forces, such as those generated by bacterial movement, in shaping the interactions between microbes and influencing the effectiveness of phage therapy.

Beyond improving the fundamental understanding of microbial ecology, the new research could be applied to enhance pharmacokinetics — the movement of drugs within the body. Further research should extend the possibilities of capitalizing on bacteria-phage relationships to develop more effective therapies against a broad range of ailments.