Bacterial warfare: Harnessing strategies bacteria use to compete with each other may lead to new antimicrobial therapies

When it comes to competition for space and nutrients, certain bacteria really do not like to share. A new study by University of Iowa researchers shows that when the bacterium Pseudomonas aeruginosa senses the presence of other bacterial species they attack, streaming toward the colonies of the other bacteria, invading and destroying them.

The UI team led by Dominique Limoli, PhD, assistant professor of microbiology and immunology in the UI Carver College of Medicine, hopes that identifying and understanding the strategies used by bacteria when they interact with one another might lead to new approaches for treating bacterial infections that threaten human health.

In general, disease-causing bacteria (pathogens) like Pseudomonas aeruginosa (P. aeruginosa) must either compete or cooperate with other resident bacteria to establish an infection. These inter-species interactions can have a dramatic effect on both bacterial survival and disease outcomes for the patient. For example, when P. aeruginosa and another bacterium Staphylococcus aureus (S. aureus) co-infect the lungs of people with cystic fibrosis (CF) they can increase the production of factors that make patients sick and can become resistant to antibiotic treatment. Bacterial lung infections are a major cause of illness and death in CF.

Using live imaging of bacterial interactions on a single-cell level, Limoli’s team investigated how P. aeruginosa and S. aureus sense and respond to each other during initial encounters. The findings were published Nov. 12 in the journal eLife.

The study suggests that P. aeruginosa senses molecules secreted by S. aureus and responds by moving rapidly towards S. aureus using small appendages called pili to crawl across the surface. When the P. aeruginosa reach the S. aureus colonies, they invade and destroy them. Importantly, the researchers showed that P. aeruginosa is able to mount this aggressive response to an array of different bacterial species and strains recovered from a variety of sources, including patients with CF, suggesting that this may be a universal tactic used by P. aeruginosa to compete against other bacterial species.

“By understanding the early interactions between these bacterial species, we may be able to design new therapies to either prevent or treat bacterial infections like the ones that threaten patients with CF,” Limoli says. “For example, if we could prevent P. aeruginosa from sensing S. aureus, we might be able to block the negative effects that occur when these bacteria co-infect a patient. And on the other hand, drugs that mimic P. aeruginosa’s ability to track down and kill S. aureus may provide a new strategy to eradicate this difficult to treat pathogen.”

The study also provides a platform to investigate single-cell interactions between other bacterial species and aid discovery of new bacterial behaviors that would not have been predicted from traditional bacterial studies.

In addition to Limoli, the research team included Elizabeth Warren and Kaitlin Yarrington at the UI, and Niles Donegan, Ambrose Cheung, and George O’Toole at the Geisel School of Medicine at Dartmouth.

The study was funded by grants from the Cystic Fibrosis Foundation and the National Institute of Allergy and Infectious Diseases.