Antibacterial drugs are crucial for treating infections, but bacterial resistance has made current treatments less effective. Researchers have developed a modified version of darobactin, derived from the entomopathogenic bacterium Photorhabdus khanii HGB1456, showing promise as an antibacterial treatment. In animal trials, the modified compound demonstrated effectiveness against drug-resistant bacteria, including E. coli.

Darobactins interact with BamA, a transmembrane protein. The researchers find that darobactin inhibits this outer membrane protein, which results in inadequate protein insertion and folding into the outer membrane and ultimately cell death.

Previously, researchers have demonstrated that genetically engineered darobactins, specifically D22, have antibacterial properties, inhibiting A. baumannii growth in lab assays.

In this latest study, Müller and Herrmann evaluated the modified D22 against a number of critical bacterial infections in animals. They found that D22 treatment eradicated A. baumannii infection in zebrafish embryos as successfully as ciprofloxacin, a broad-spectrum antibiotic. The study also involved multiple efficacy and dosing trials.

According to the study, injecting D22 proved more effective than taking it orally. While P. aeruginosa bacterial growth in mice was inhibited by repeated D22 dosages, the infection was not entirely eradicated. In multi-dose tests against E. coli, injecting D22 four times in 25 hours effectively eliminated E. coli in a severe peritonitis infection scenario. Twice-daily injections administered over three days drastically decreased bacterial presence in a complex E. coli urinary tract infection.

These findings demonstrate D22’s ability to inhibit very significant infections and highlight the compound’s potential for further development into clinical trials.