Finally Some Good News on Antibiotic-Resistant Bacteria

A weak spot in enzymes responsible for causing antibiotic resistance has been pinpointed, according to a team of researchers from the University of North Carolina in Charlotte (UNC Charlotte).

Lead authors Dennis R. Livesay, PhD, and Jenna R. Brown, along with their colleagues, identified 4 protein structures of the class C beta-lactamase enzymes which have evolved to be less sensitive to medications. In addition, all 4 molecules were found to have similar rigid protein superstructures and comparable quantitative stability/flexibility relationships (QSFR) — a characteristic that is very unusual despite the fact that each of them is found in proteobacteria.

“Clearly this result is important because it is at the active site, because it is evolutionarily conserved, and because we have never seen this degree of conservation in any other system before,” Livesay, a bioinformatics and genomics professor at UNC, said in a news release.

The team utilized the complex modeling program created at UNC Charlotte, Distance Constraint Model (DCM), to capture details on the proteins’ structures. By studying their properties and behaviors, the authors were able to learn more about the separate sequences made up of amino acids. Previous research conducted by the team where they also used the DCM revealed that “evolutionary changes in the structure of the enzyme had no relation to the specific antibiotics the enzyme was effective in dismantling.”

According to the new findings published in PLOS ONE, not only did the 4 proteins have considerably similar structures, but 3 “’flexible structural elements at the active site” — which is the place where antibiotics are processed – were found as well.

“From an evolutionary perspective, this is really cool,” Livesay explained. “Here’s a protein that has a very intense set of evolutionary pressures on it, making these coupling critical and not allowing them to vary. We’ve never seen that before.”

This means that this comprised section may allow researchers to interfere with enzymes to counteract the resistance in the future.

“If you were able to disrupt that coupling, there is a good likelihood that you would have a nice therapeutic effect,” Livesay said.

A question that remains unanswered, but may possibly act as a stepping stone for the next round of research, is the reason behind the abnormal QSFR similarities.