The creation of antibiotics with improved target selectivity against bacteria, and potentially less adverse side effects, is reported this week in Nature Communications. The new antibiotics could lead to less toxic and more effective antimicrobial therapies.
Aminoglycoside antibiotics attack bacteria by binding to their ribosomes - the essential machines that make proteins within cells. However, human cells also contain their own ribosomes, and sporadic off-target binding to these human ribosomes leads to adverse side effects in some patients. Erik Bottger, Andrea Vasella and colleagues modified existing aminoglycosides and found that the resulting compounds were less toxic to cultured human cells than commonly used aminoglycosides. Moreover, the new compounds retained antibiotic activity when used against disease-causing Staphylococcus aureus in infected mice. The lower toxicity was associated with increased selectivity against bacterial ribosomes and lower activity against human ribosomes.
This work represents an important step towards the development of less toxic aminoglycoside antibiotics.