Researchers at St. Jude Children’s Research Hospital demonstrated that a Staphylococcus aureus-specific antibiotic called Debio 1452 (produced by Debiopharm International) effectively spared much of the gut microbiome when given orally to mice.
According to study author Charles Rock, “in this study, we demonstrated that the pathogen-selective approach to antibiotic development is an effective way to minimize collateral damage to beneficial bacteria in the gut microbiome. Such treatment strategies will become increasingly important for use in antibiotic drug design thanks to the growing awareness of the vital role that the gut microbiome plays in digestion and immune protection.”
The antibiotic works by blocking the activity of an enzyme called FabI. Staph needs this enzyme to grow, but most other bacteria do not.
The group compared the effect of Debio 1452 and broad-spectrum antibiotics (linezolid, clindamycin, amoxicillin, of moxifloxacin) on the gut bacteria of mice. They used next-generation sequencing techniques to identify and quantify bacteria from stool samples.
The broad-spectrum antibiotics decreased the abundance of gut microbes up to 4,000 fold! (That’s a lot.) Debio 1452, on the other hand, had little effect. What’s more, the concentration of Debio in mice was 12 times higher than what would be given to humans!
Broad-spectrum antibiotics also decreased the diversity of gut bacteria, but Debio 1452 altered diversity very little. Interestingly, the quantity of bacteria depleted with the broad-spectrum antibiotics returned to normal within a week, but diversity remained skewed.
This pathogen-specific approach does have an obvious drawback, however. It requires researchers to identify factors - enzymes, for example - that are essential to each pathogen and design a drug to specifically target that weakness.
Sources: Antimicrobial Agents and Chemotherapy, Alpha Galileo