Generation of Novel Fungicidal Activity by the Combined Actions of Hygromycin B and Polymyxin B

Abstract

The aminoglycoside antibiotic hygromycin B (HgB) has been widely used in veterinary medicine and in cell culture selection. HgB kills bacteria, fungi, and higher eukaryotic cells by inhibiting protein synthesis. A marked synergistic relationship was observed between HgB and the bactericidal antibiotic polymyxin B (PMB) in their ability to cause cell death of Saccharomyces cerevisiae, but this was not observed when S. cerevisiae cells were treated with PMB and a different aminoglycoside selective for prokaryotic organisms. However, the combined lethal actions of HgB and PMB did not depend on the inhibition of 80S ribosomal protein synthesis, even if the ribosome-binding OH of HgB is similarly involved in its PMB-dependent fungicidal activity. Our findings could have implications for improving the use of HgB in veterinary medicine.