New Method for Discovering Antibiotics Could Accelerate Discovery of New Drugs

A new method for identifying and characterizing antibiotics could lead to the discovery of new antibiotics capable of treating infections currently resistant to all other forms of treatment.

Ever since the invention of penicillin in the late 1920s, researchers have been locked in a high-stakes arms race against ever-evolving strains of bacteria. Over the last quarter century, however, scientists have fallen behind, with the number of new antibiotics entering the clinic falling drastically. The effects of this lag became painfully obvious when a 2011 outbreak of Klebsiella at the US National Institutes of Health Clinical Center signified the bacteria had evolved resistance even to a "last resort" drug known as colistin.

Just this week the Centers for Disease Control and Prevention issued a report in which it estimated that 2 million people become infected with antibiotic-resistant infections annually, some 23,000 of whom die as a result.

"We are finally running out of the miracle drugs," Joseph Pogliano, a biology professor at the University of California, San Diego and head of the new study, said in a statement.

One of the main challenges in identifying new antibiotics and bringing them to market is determing precisely how the molecules work.

"It's easy to identify thousands of molecules capable of killing bacteria," explained Kit Pogliano, a professor of biology and a co-author 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."

Key to this process is understanding how the drug works, she explained -- a process that usually requires months. The new method, in contrast, reduces this phase of research to mere hours.

"We've applied 21st century methods that within just two hours provide this information, allowing more rapid prioritization of new molecules," she said. "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 crucial aspect to this new approach, which the researchers describe as an autopsy on bacterial cells, is 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, but now that we have the method working, it is very exciting," said 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."

In the end, the method represents a game changer to the work of drug development, according to the researchers.

"This method will allow us to more quickly identify chemicals that kill bacteria, which will accelerate the development of new medicines," Joseph Pogliano said, adding that "Understanding how antibiotics work is key to understanding how they evolve resistance."