A bacterial antibiotic resistance gene with eukaryotic origins

Here, we show that a gene known to convey antibiotic resistance in bacteria was apparently transferred from an early evolved eukaryote. Mupirocin, a topical agent widely used since 1985 against skin surface and nasal colonization by the Gram-positive bacterium Staphylococcus aureus, is the natural compound pseudomonic acid produced by the bacterium Pseudomonas fluorescens NCIB 10586. In the early 1990s, much higher levels of mupirocin resistance in S. aureus appeared in some clinical settings, where estimated MICs exceed 512 mg/L. Highly resistant strains have a second copy of the IRS gene (IRS-HR), located on an extrachromosomal plasmid, the product of which is highly divergent (34% amino-acid identity) from those of sensitive or moderately resistant IRS genes (IRS-S/MR). More recently, another Gram-positive bacterium, Mycobacterium tuberculosis, was shown to be highly resistant to mupirocin, and the product of its chromosome-located IRS gene had higher sequence similarity to S. aureus IRS-HR proteins than IRS-S/MR proteins. Using the S. aureus IRS-HR sequence as a probe against public databases, we discovered four more bacterial IRS-HR-type genes.