UAH – News

In addition to using the structure as a platform to generate antibiotics, researchers can also use it to design new sensors for molecules of interest, says Dr. Luis Rogelio (Roger) Cruz-Vera.

Michel Mercier | UAH

Research conducted by the University of Alabama at Huntsville (UAH) has for the first time identified the precise operational genetic structure of a key system in Escherichia coli (E. coli) bacteria, opening the door to possible new antibiotics to treat the infections it causes.

“The gene we studied is involved in the production of a bacterial hormone which is important for bacterial colonization. This hormone induces the production of sticky substances used by bacteria to adhere to inert surfaces, as well as to plants and animal tissues ”, explains Dr Luis Rogelio (Roger) Cruz-Vera, associate professor at the Department of Biological Sciences of the ‘UAH, part of the University of Alabama system.

“Our new structure will be used in future studies to obtain compounds capable of modulating the production of this hormone in bacteria, thus reducing bacterial colonization by modifying the bacterial cell’s ability to attach to surfaces and reduce communication with other cells. “

The most contagious E. coli cases are mild and lead to vomiting, diarrhea, cramping and fatigue, but some strains can cause serious illness and even life-threatening complications.

In 2015, Dr Cruz-Vera teamed up with Dr Emily Gordon and Dr Arnab Sengupta, both of whom were doctoral students in the UAH’s Biotechnology Science and Engineering program at the time, and whose work during their graduate studies produced the genetic and biochemical tests. used in the research paper the trio wrote with other collaborators. The research was funded by the National Science Foundation.

The two doctoral researchers graduated in the summer of 2015. Currently, Dr Gordon is an associate researcher at the HudsonAlpha Institute for Biotechnology and Dr Sengupta is an assistant professor at Georgia State and College University in Milledgeville, Georgia.

“We have determined with great precision the site of interaction of tryptophan, an essential amino acid, at its molecular sensor,” explains Dr. Cruz-Vera. “Bacteria use the protein-making machines called ribosomes as sensors for small molecules like tryptophan,” he says. “Bacteria sense their environment, as we do for example with our nose, to detect molecules that will be used as food. “

E. coli and other bacteria can detect L-tryptophan, then the sensor induces the expression of two genes, one which helps the bacteria to get L-tryptophan inside its cells and another which transforms L-tryptophan in energy and adhesion hormone.

“We got the most precise operational structure out of this system,” says Dr. Cruz-Vera.

The molecular complex as found in bacteria is not stable enough to give an idea of ​​how L-tryptophan interacts with the ribosome using current structural approaches, and this has hampered previous attempts by two different scientific groups.

To accurately identify the structure, Cruz-Vera’s group and collaborating scientists used genetic tools to isolate mutants that produced a more efficient tryptophan sensor. They then used biochemical approaches to discern which mutants were the most effective at detecting tryptophan. Finally, they identified structural approaches to determine the location of L-tryptophan in the ribosome.

If this system is disturbed by an antibiotic still to develop, then E. coli cannot attach to tissue and cannot communicate with other bacteria.

“Our future goals include testing several compounds, based on computer analysis, to find possible molecules that can block the interaction of tryptophan, which will reduce the expression of genes that produce the bacterial hormone,” explains Dr. Cruz-Vera.

In addition to using the structure as a platform to generate new antibiotics, researchers can also use it to design new sensors for molecules of interest, he says.

“This is an objective that my group shares with the group of Dr Jérôme Baudry,” Dr Cruz-Vera. “We would like to generate customizable biosensors, which could be used for molecular detection and bioremediation. “

Molecular biophysicist and UAH professor, Dr Baudry is the Ms. Pei Ling Chan Chair in the Department of Biological Sciences and has experience in drug discovery and computational biology.

Dr Cruz-Vera says his group has been studying this complex since he started at UAH in the summer of 2007.

“I am recognized around the world for all of my work on this complex,” he says. “My group generated the genetic and biochemical analyzes, and once we got them, I worked with three other globally recognized groups to get the end product, the structure of the complex. “

Collaborators include Texas A&M University, University of Chicago, and University of Bordeaux in Pessac, France.

“I am delighted that the UAH and the Department of Biological Sciences have collaborated with world-renowned groups in my area of ​​expertise,” said Dr Cruz-Vera. “This could lead to more of these articles in the near future. “

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