Scientists at the University of California-San Diego report that they have found a novel method for identifying and characterizing antibiotics. Their findings might lead to the discovery of new antibiotics for the treatment of antibiotic-resistant bacteria, according to the researchers.
The investigators published their findings in this week's early online edition of the Proceedings of the National Academy of Sciences. They say they made their discovery by developing a method to perform the equivalent of an autopsy on bacterial cells.
“This will provide a powerful new tool for identifying compounds that kill bacteria and determining how they work,” explained Joseph Pogliano, Ph.D., a professor of biology at UC San Diego who headed the research team. “Some bacteria have evolved resistance to every known class of antibiotic and, when these multi-drug resistant bacteria cause an infection, they are nearly impossible to treat. There is an urgent need for new antibiotics capable of treating infections caused by antibiotic- resistant bacteria.”
The UC-San Diego study comes at a time when increasing numbers of antibiotic-resistant bacterial outbreaks are taking place at hospitals all across the U.S. “We are finally running out of the miracle drugs,” noted Dr. Pogliano.
Over the last 25 years, the number of new antibiotics entering the clinic has drastically declined. At the same time, bacteria have continued to evolve resistance to all of the currently available drugs, creating the current critical situation. One of the main problems in identifying new antibiotics and bringing them to market is a lack of understanding how the molecules work.
“It’s easy to identify thousands of molecules capable of killing bacteria,” said Kit Pogliano, Ph.D., a professor of biology and a coauthor of the paper. “The hard part is picking out the winners from the losers, and choosing molecules that are the best candidates for drug development.”
To better understand how drugs work requires months of intensive work, she pointed out.
“We’ve applied 21st century methods that within just two hours provide this information, allowing more rapid prioritization of new molecules,” she continued. “This will open up the discovery pipeline, allowing us to more rapidly identify new molecules with potential to enter the clinic for treatment of multi-drug-resistant pathogens.”
One key to this new approach was the combination of microscopy and quantitative biology tools.
“We had to develop all of the cell biology and quantitative biology methods for generating the data ourselves and that required a lot of work,” noted Poochit Nonejuie, a graduate student in the division of biological sciences and another co-author. “My chemistry colleagues can give me a new molecule in the morning, and by the afternoon I can tell them the likely cellular pathways that they target. It's mind blowing how powerful the technology is.”
“Our new method represents the first time that a single test can be performed and identify the likely mechanism of action for a new compound,” said Dr. Joseph Pogliano, adding that the technique requires just a few nanograms of each drug candidate.
“This method will allow us to more quickly identify chemicals that kill bacteria, which will accelerate the development of new medicines,” he pointed out. “Understanding how antibiotics work is key to understanding how they evolve resistance.”