Living in Biofilms Causes Bacteria to Diversify

Findings from University of Iowa researchers show that bacteria have learned that there is strength in diversification. When disease-causing bacteria assemble into communities known as biofilms, the individual bacteria rapidly diversify. This diversity increases the capabilities of the group and provides a form of "biological insurance," which protects the organisms from adverse conditions. The findings will appear this week in the Proceedings of the National Academy of Sciences.

In the past few years, researchers have found that bacteria living in biofilms are responsible for many chronic human infections such as cystic fibrosis lung infections, heart valve infections and wound infections in people with diabetes. In biofilms, organisms live clustered together, encased in a self-produced slime.

"Biofilm infections are a major medical problem, and one focus of our lab is to understand why the biofilm lifestyle makes bacteria so difficult to eradicate," said Pradeep Singh, MD, assistant professor of internal medicine and microbiology in the UI Roy J. and Lucille A. Carver College of Medicine and the study's principal investigator.

Previous work has shown that living in groups gives the bacteria properties they do not have as individuals, including increased tolerance to antibiotics. The new findings suggest biofilm growth may provide another key advantage.

Using a laboratory model, the UI team found that when biofilm communities were established using a small number of identical bacteria, a remarkable degree of diversity rapidly developed in the population.

"After only a few days of biofilm growth, the bacteria diversified in their nutritional requirements, ability to swim, capacity for dissemination, production of protective substances, as well as in other traits," said Matt Thoendel, a UI medical and doctoral student who contributed to the work.

"This was very surprising," said Blaise Boles, UI graduate student and another of the study's authors. "Even more fascinating was that diversification was only generated when the bacteria assembled into communities."

This finding led the researchers to draw parallels to other biological communities in which diversity has been studied.

"It's well known that diversity can enhance the functioning of many types of communities," said Singh, who also is a physician and researcher with the Department of Veterans Affairs Iowa City Health Care System. "This idea is known as the 'insurance hypothesis', and it predicts that diversity will improve community functioning because the likelihood is increased that some subpopulation will thrive as environmental conditions change."

The insurance hypothesis springs from observations in natural ecosystems. For example, forests made up of diverse species are much more resistant to drought or insect attack than those in which a single species dominates.

"We wondered if the diversity generated in biofilms could have similar effects," Boles said. "To test this, we genetically engineered bacteria so that they were unable to diversify. Just as the insurance hypothesis predicted, blocking diversification weakened the biofilm communities."

"This finding raises the intriguing possibility that bacteria may have evolved mechanisms to produce diversity when they sense they are part of a group," Singh said.

The study results may also shed light on why chronic infections caused by biofilms are so difficult to eradicate.

"If this type of diversification occurs in human infections, it could dramatically increase the capability of the infecting bacteria," Singh said. "Instead of clones with set capabilities, many different sub-populations of bacteria may exist in an infection, and each may have different strengths."

Understanding how diversity is generated in biofilms may lead to strategies to block this generation of diversity and ultimately make the biofilms susceptible to treatments.

Funding for the study included support from the Cystic Fibrosis Foundation and the National Institutes of Health.

Source: University of Iowa (Health Sciences)