Research on bacterial mechanism may lead to new antibiotic development

RyanLab_DavidGalvez_Courtesy
David Galvez/Courtesy

A group of researchers from UC Berkeley and the University of Massachusetts Amherst may have opened the doors to new antibiotic drug development by discovering how bacteria control their cell cycle.

The researchers — including Kathleen Ryan, a campus associate professor of plant and microbiology, and Peter Chien, a professor of biochemistry and molecular biology at the University of Massachusetts Amherst — were able to pinpoint the molecular mechanics of the cell cycle, or the process of bacterial growth and division. They did so by outlining regulated protein degradation, in which enzymes called proteases destroy specific proteins to adapt to a changing environment — a process vital to bacterial invasion and virulence, the relative ability of a microorganism to bring in a disease.

Ryan explained that sometimes, a bacterium changes from one particular type of cell to another due to an event, requiring the destruction of proteins from a previous state.

“Since destroying all the copies is an extensive process — it costs energy and (the proteins) could have important functions — you want that protein destruction function to be diligently regulated,” she said.

The research article, authored primarily by Stephen Smith, a former graduate student at UC Berkeley who worked in Ryan’s lab, was published in an online edition of the Proceedings of the National Academy of Sciences last week.

Chien explained that the research’s importance to antibiotic development stems from the fact that almost all virulent bacteria require protein destruction to invade their hosts. He said that their results illustrated a new mechanism that allows a protein-destruction pathway to be triggered by particular changes.

“Importantly, these changes only come about at a specific time during the life cycle of the bacteria,” Chien said in an email. “The cell conditions have to be just right in order for the … protease system to be fully active for degradation of the target proteins.”

Ryan, who has been working on this project since she started her postdoctoral research at Stanford University, was elated by the results. They revealed the roles and functions of additional “accessory” proteins, which play indirect roles in viral functions.

“I was super excited that we saw something, because it seems like it should be an easy process for one protease to chew up one protein — and it does — but in the cell, there are three additional proteins, the accessory proteins, that are required for it to happen,” Ryan said. “Before our work, no one had seen the accessory proteins having an effect.”

Scientists such as Andreas Martin, a campus assistant professor of biochemistry, believes Ryan and Chien’s research will contribute to the development of new antibiotics. Martin explained that because their findings revealed important details about several bacterium’s life-cycle regulation, the research has great potential in helping develop antibiotics.

Ryan suggested that the research could not only have applications to bacteria that are damaging or pathogenic but could also apply to bacteria with potential beneficial effects as well, such as those that help produce a nitrogen source for plants.

Both Ryan and Chien hope to continue their research to further study the bacterial stress responses. They will be searching for new pathways that can block the negative influence of bacteria to prevent bacteria from resisting antibiotics.

Tahmina Achekzai covers research and ideas. Contact her at [email protected] and follow her on Twitter @tahminachekzai.

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