An important bacterial protein called UmuD may help prevent antibiotic resistance, scientists say.
Penny Beuning from Northeastern University’s college of science and colleagues are studying UmuD that regulates mutagenesis and may provide important clues about how to stop the process that eventually results in antimicrobial resistance.
Using the bacterium E coli as a model, she has learned that UmuD interacts with the machinery that replicates DNA, and, when altered, may provide the switch that triggers mutation.
UmuD exists in two forms, a full length version when first expressed, and later, if DNA is damaged, a much shorter form. It is this shorter version that allows bacteria to mutate.
Once there is DNA damage, “there is an SOS response, and the levels of some specific proteins go up. There is a massive stress response, and UmuD responds by cutting its arms off,” Beuning said.
In cells where only the full-length version of the protein is present, the bacteria cannot mutate.
“But when it forms its shorter self, the cells are mutable,” she said.
The fact that UmuD is not present outside bacteria makes it a viable antibiotic target.
“The hope would be to find something that targets UmuD together with an existing antibiotic to prevent bacteria from mutating and developing a resistance to that particular drug,” Beuning said.
“Among the things we have been looking at: how does UmuD work, and what controls the cleavage of the arms?” she said.
Beuning specifically is looking at the cleavage process of UmuD using gel electrophoresis, which separates proteins according to size.
“UmuD is a small protein – 139 amino acids – which loses 24 amino acids from the arm. So it goes from 139 to 115,” she said.
“We can observe this difference with electrophoresis, allowing us to determine how different conditions or other proteins might affect UmuD cleavage,” said Beuning.
The team is studying different UmuD protein interactions in the lab, using biochemistry to see when and how different proteins bind to one another.