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Can Targeting Bacteria’s Senses Help Fight Resistance to Antibiotics?

Antibiotic-resistant bacteria are a growing problem in healthcare. But what if scientists could find ways to stop infections without triggering the antibiotic resistance that can result from destroying the bacteria?

That’s one of the potential applications of research at the Advanced Science Research Center at The Graduate Center, CUNY. A new study published in the Proceedings of the National Academy of Sciences illuminates how blue light activates sensor proteins in a certain bacterial species. Knowing how these sensors work is a step on the path to developing antibiotics that target such sensors.

The researchers studied a sea-dwelling bacterial species called Erythrobacter litoralis. Specifically, they looked at a blue light-sensing histidine kinase protein within the bacteria. Though the protein examined in the study responds to light, other histidine kinases can sense things like pH or osmotic pressure. These proteins also translate their sensory information into responses. Some of these sensors are thought to be critical to the bacteria’s virulence, so interfering with them could cut short the bacteria’s ability to infect.

To learn how the light-sensing protein does this translation, the scientists examined how it structurally changes under blue light. They are studying this protein in E. litoralis as a model, and plan to expand their research to learn about other histidine kinases in other bacteria that could be good antibacterial targets.

“We believe some of the more complex, pathogenetic bacteria that live in the gut may also take their cues from light stimulation,” said Igor Dikiy, a postdoctoral researcher at the ASRC and first author on the paper, “so studying this light-sensing process in E. litoralis is a good place to begin understanding how such bacteria ‘turn on’ the ability to infect us.”

Taking aim at bacterial sensors, Dikiy said, could allow researchers to stop the bacteria’s infectious properties without killing the bacteria outright. While killing bacteria puts selective pressure on them to develop resistance abilities, scientists hope that sensor-targeting antibiotics would avoid this. Ideally, these antibiotics would also avoid killing the beneficial bacteria that live in our bodies.

The paper’s authors also include Professor Kevin Gardner, director of the ASRC’s Structural Biology Initiative, Research Assistant Professor Rinat Abzalimov, and Ph.D. student Uthama Edupuganti.

Beyond SUM

Explore This Work

Insights into histidine kinase activation mechanisms from the monomeric blue light sensor EL346
Proceedings of the National Academy of Sciences, 2019

Work By

Kevin Gardner (Einstein Professor, Chemistry and Biochemistry) | Profile 1
Igor Dikiy (NIH Postdoctoral Fellow, Biochemistry) | Profile 1