Chemists are in a constant race. While chemists work on synthesizing new antibiotics, the bacteria quickly develop their own antibiotic resistance. Developing antibiotics for certain bacteria with thin cell walls, called gram-negative bacteria, has proven particularly challenging. Of the 20 classes of antibiotics developed in the past 20 years, none have targeted gram negative bacteria, such as E. coli.

Researchers from Princeton University recently developed a molecule capable of acting as an antibiotic against gram-negative bacteria. This molecule, named SCH-79797, stops bacterial cells on two fronts: the bacteria can no longer synthesize a derivative of folic acid, which they need to build their DNA, and the bacterial cell membranes are weakened, causing the death of the bacterial cells.

Because the antibiotic was killing cells by two different pathways, the bacterial cells struggled to evolve ways to survive exposure to SCH-79797. The researchers allowed bacterial cells 25 days to grow and reproduce while repeatedly exposing the cells to the drug and were not able to measure any antibiotic resistance. For reasons that are not entirely understood, SCH-79797 was more effective at killing bacterial cells than combinations of two different drugs that split the work of blocking the folic acid pathway and damaging the cell membrane.

SCH-79797 proved too toxic in human cells to move to animal trials, so the researchers synthesized a new molecule with a similar chemical structure called Irresistin-16. This molecule was injected into mice who had been infected with a highly antibiotic-resistant chlamydia bacteria strain. Irresistin-16 was able to cure mice of the chlamydia infection. This work indicates that future work developing molecules that target the folic acid pathway or multiple pathways with the same molecule hold promise for the continuing race against antibiotic resistant bacteria.

Corresponding Author: Emily Kerr

Popular Press Article: ‘Poisoned arrow’ defeats antibiotic-resistant bacteria

Scientific Article: A Dual-Mechanism Antibiotic Kills Gram-Negative Bacteria and Avoids Drug Resistance

Image Credit: Microrao: Antibiotic Restraint Bacteria Wikicommons