Light Found to Suppress Virulence in Superbug Study

University of Chicago

Light is a universal stimulus that influences all living things. Cycles of light and dark help set the biological clocks for organisms ranging from single-celled bacteria to human beings. Some bacteria use photosynthesis to convert sunlight into energy just like plants, but other bacteria sense light for less well-known functions.

In 2019 , Sampriti Mukherjee, PhD , and her team at the University of Chicago discovered that far-red light, part of the light spectrum near the infrared range, prevents the formation of biofilms by the human pathogen Pseudomonas aeruginosa. Biofilms form when communities of bacteria cluster together and attach to surfaces like medical devices or tissues. Pseudomonas aeruginosa is an antibiotic-resistant bacterium, normally found in the soil and water, that is known to cause difficult to treat infections in hospitalized patients, especially those with weakened immune systems, lung diseases, or large wounds like burns.

Figuring out how to prevent this pathogen from forming biofilms could help treat these dangerous infections. In a new study published recently in Nature Communications , Mukherjee's team learned more about how light affects its behavior. They show that a small protein triggers a photo-sensitive cascade that activates genes to suppress biofilms and virulence in Pseudomonas aeruginosa. This photo-sensing system is also present in other Pseudomonas bacteria, suggesting that it has more undiscovered functions.

"Photo sensing in non-photosynthetic bacteria is such poorly chartered territory," said Mukherjee, who is an Assistant Professor in the Department of Molecular Genetics and Cell Biology. "Here we found a new signaling system in this bacterium and it's connected to biofilms and virulence. It's also present in other pseudomonads, so it gives us the opportunity to translate our findings and possibly learn how to suppress infections."

During the COVID-19 pandemic, you may have seen news stories about technology used to shine blue or UV light in hospital rooms to kill viruses and bacteria. While far-red light isn't toxic to bacteria in the same way, it does act as a signal. Mukherjee and her team wanted to understand more about how Pseudomonas aeruginosa was using light to suppress biofilms, so they attached a Luciferase reporter gene that produces its own light to a promoter for the genes that produce virulence factors. When they exposed the bacteria to far-red light, the reporter was not activated, meaning those genes were not expressed. They also engineered a version of the bacterium with mutations to disrupt the photo-sensing cascade and saw it produced more of the virulence factors.

During those screens, Dimitrios Manias, a graduate student in Mukherjee's lab and lead author of the study, identified a new, unknown gene that was being expressed when they shone far-red light on bacteria. This gene encodes for a small protein called DimA located in between the inner and outer layers of the bacterium's cell membrane, which appears to kick off a chain of protein processing that activates the transcription factors that ultimately suppress biofilms and virulence.

"Now we have a positive regulator of the system, so you can imagine a situation where we could artificially over express this small protein and see if we can prevent biofilm formation," Mukherjee said.

The team also found several unknown genes that were activated by light, which suggest that this photo-sensing cascade could have other uses in Pseudomonas species. Mukherjee hypothesized that it could be a mechanism for controlling responses to naturally varying light. In the soil, for example, bacteria on the roots of plants could sense how deep there were by the amount of light. Infectious bacteria inside a hospital patient's lungs could thrive and form biofilms in the absence of light. Her team wants to learn more about the role of the small protein and the many other genes activated by light.

"Light is variable in nature, so you can have cloud cover, for example, and perhaps the bacterium doesn't want to stop photo sensing immediately," she said. "But then if there's no more light coming in, it also doesn't want to run the photo sensing genes for forever, so it stops. This could be like an hourglass model where the process slowly runs out with the light."

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