The idea of bacteria coming together to form a socially organized community capable of cooperation, competition, and sophisticated communication may at first glance sound like science fiction — or just plain crude.
But biofilm communities have important implications for human health, ranging from disease to aiding digestion. And they play a role in a range of emerging technologies aimed at protecting the environment and generating clean energy.
New research led by UCLA could give scientists information that will help them grow useful microbes or remove dangerous microbes from surfaces where biofilms have formed, including on tissues and organs in the human body. The study, published in the Proceedings of the National Academies of Sciences, describes how when biofilms form, bacteria communicate with their progeny using a chemical signal analogous to radio transmissions.
The researchers showed that the concentration levels of a messenger molecule called cyclic diguanylate, or c-di-GMP, can rise and fall in well-defined patterns over time and across generations of bacteria. Bacterial cells use these chemical signal waves, according to the study, to encode information for their progeny that help coordinate colony formation.
In this phenomenon, whether a given cell attaches to a surface is influenced by the specific shape of these oscillations – much like how information is stored in AM and FM radio waves.
“Because these oscillations orchestrate what the whole lineage is doing, large numbers of cells are being controlled with these signals at once,” said corresponding author Gerard Wong, professor of bioengineering at UCLA Samueli School of Engineering and chemistry and biochemistry at UCLA College, and a member of the California Institute for Nanosystems at UCLA. “This means we potentially have a new button to control or fine-tune biofilm formation, which functions as mass communications for bacteria.”
Stopping biofilm formation could save lives in certain scenarios, such as fighting infections lining the lining of the lungs in people with cystic fibrosis.
In other situations, improving the ability to grow biofilms would be helpful – fortifying colonies of “good” bacteria in the human gut to help with digestion, for example, or to protect people from disease-causing microbes. . And scientists and engineers, including several at UCLA, are working to develop bacterial biofilms that can break down plastic, eat industrial waste, or even generate electricity in a fuel cell.
The study adds new dimensions to the scientific understanding of the mechanisms that lead to biofilms. The current paradigm, established over the past 20 or so years, holds that when a bacterium senses a surface, that cell begins to produce c-di-GMP, which in turn causes the bacterium to attach to the surface. Indeed, biofilm cells generally have higher levels of c-di-GMP than bacteria cells that move around a lot.
Biofilm research focusing on the ability of bacteria to communicate across generations was pioneered by first author Calvin Lee, a postdoctoral researcher at UCLA, along with Wong and their teammates, in a 2018 publication. In the current study, the team elucidates how bacteria communicate about the existence of a surface using c-di-GMP signals: Signal waves of different heights and different frequencies can be transmitted through a cell to his descendants.
These chemical signals are analogous, respectively, to AM radio — amplitude modulation, which encodes a given signal based on the amplitude or pitch of a radio wave — and FM radio — frequency modulation , which encodes signals by the number of oscillations in the wave over a given period of time.
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Using analysis techniques typically used in big data and artificial intelligence, the researchers identified three important factors that control biofilm formation: average levels of c-di-GMP, frequency of oscillations of c-di-GMP levels, di-GMP and the degree of cell movement at the surface where the biofilm forms.
“The existing paradigm is that an input produces an output, with increasing levels of signal leading to biofilm formation,” Lee said. “We propose that multiple inputs ultimately lead to the same output and that bacteria can leave lasting messages for their progeny. You have to look at more things to get the full picture.
The study’s other co-authors are graduate students William Schmidt and Jonathan Chen from UCLA, and graduate student Shanice Webster and Professor George O’Toole from Dartmouth College.
The study was supported by the National Institutes of Health, the Army Research Office and the National Science Foundation.