To contend with the alarming rise in antibiotic-resistant bacteria, a team of Princeton University, US, researchers have introduced a first-of-a-kind compound that works like a “poisoned arrow” after years of experiments using a range of classic and cutting-edge imaging and assay techniques. The “arrow” of the new molecule, SCH-79797, can penetrate the protective outer layers of bacteria while its contained “poison” can tear up the delicate bacterial contents.

SCH-79797 is able to overcome the two main types of bacterial infections that endanger human health: Gram-positive and Gram-negative bacteria, classified based on the structure of bacterial cell walls. Gram-negative bacteria, in particular, feature a robust protective outer layer that repels the advances of most antibiotics. The Princeton researchers found that SCH-79797 can not only pierce the protective layer of Gram-negative bacteria, it then tears apart the folate within its cells, which it depends on to survive – the discovery is promising as it has been almost 30 years since a new class of Gram-negative-killing drugs entered the market.

The researchers additionally developed derivatives when the original SCH-79797 presented them with a significant problem. While SCH-79797 killed bacterial cells with great effectiveness, it acted with similar potency on human cells, which could prove fatal. The team came up with a derivative called Irresistin-16, which is nearly 1,000 times more potent against bacteria than it is against human cells. The Princeton teamwere able to use it to cure mice infected with a virulent strain of Gram-negative bacteria, N. gonorrhoeae.

“This is the first antibiotic that can target Gram-positives and Gram-negatives without resistance,” said Princeton’s Professor of Biology Zemer Gitai. “But what we’re most excited about as scientists is something we’ve discovered about how this antibiotic works – attacking via two different mechanisms within one molecule – that we are hoping is generalizable, leading to new and better types of antibiotics in the future.”