Findings about protein expected to help create new antibiotics

Researchers at US Oregon State University (OSU) hope to build on latest findings about a protein and to create a new class of antibiotics.

The work, published in the recent issue of the journal Structure, involves using X-ray crystallography to acquire first-ever detailed, atomic-level images of a peroxiredoxin, which is needed by all cells to help eliminate hydrogen peroxide, a toxin.

"Peroxiredoxins are found in animals, plants, and bacteria, and are proteins that are crucial for cell survival," said Arden Perkins, the lead author on the study.

However, peroxiredoxins inside bacteria help provide protection from immune cells and increase the virulence of bacterial cells that cause infections.

"The main function of peroxiredoxins is to eliminate hydrogen peroxide in cells by converting it to water," Perkins said in a news release from OSU. "This toxin is a byproduct of normal cell metabolism, and hydrogen peroxide has to be removed so it doesn't damage the cell. If peroxiredoxin doesn't do its job, cells will die."

The researchers believe if a molecule can be found that selectively blocks the motions of peroxiredoxin only in bacterial cells, it could function as an entirely new way to kill those cells and set the stage for new types of antibiotics.

With images provided by X-ray crystallography, a technique that can reveal structures down to individual atoms, the researcher found that when peroxiredoxin is restrained and loses its mobility, it also loses its function. And if the normal function is lost, it can lead to cell death.

In addition, they discovered that there are special regions on bacterial peroxiredoxins, different from those found in humans, that could be specifically targeted.

Based on these findings, they envisioned that if compounds could aim at those targets and selectively shut down the protective function of peroxiredoxin just in bacteria, it would weaken or kill bacterial cells.

"There's a lot of potential for this to be foundational work," Perkins said. "The key concept is selectively restraining the motions of peroxiredoxins in some cells, inactivating its function and leading to the death of the cells you want to kill."

The researchers hope the approach could help address the increasing problem of antibiotic resistance to many existing drugs and work in synergy with existing antibiotics to improve their efficacy.

In related approaches, Perkins said, the concept may also hold some value against certain non-bacterial pathogens, like those that cause malaria or African sleeping sickness, which increasingly are difficult to treat.