Genomics reveals global emergence of near pan-drug resistant S. epidermidis

Dr Jean Lee1

1Monash Health, Victoria, Australia

 

Staphylococcus epidermidis is an important member of the human microbiome, widely present on healthy skin, and is a well-recognised cause of hospital-associated device related infections. We noted an increase in multi-drug resistant S. epidermidis infections at our institution, and undertook a combined genomic-phenotypic analysis of a global collection of drug-resistant isolates. Using genomics we reveal that three multidrug resistant, hospital-adapted lineages of S. epidermidis (two ST2 and one ST23) have emerged in recent decades and spread globally. Resistant to multiple classes of antibiotics (beta-lactams, aminoglycosides, quinolones, macrolides, and fusidanes), these multidrug resistant clades are also resistant to rifampicin through acquisition of a specific rpoB mutation that has become fixed in these populations. Analysis of 419 isolates collected from 96 institutions in 24 countries identified a dual RpoB substitution (D471E/I527M) to be the most common cause of rifampicin resistance in S. epidermidis, accounting for 86.6% of mutations.

Furthermore, we reveal that the D471E/I527M dual substitution occurs almost exclusively in isolates from the ST2 and ST23 lineages. By breaching lineage-specific DNA restriction modification barriers and then performing site-directed mutagenesis, we show that this rpoB mutation not only confers rifampicin resistance, but also reduced susceptibility to the last-line glycopeptide antibiotics, vancomycin and teicoplainin. Our study has uncovered the previously unrecognised international spread of a near pan-drug resistant opportunistic pathogen. It is possible that hospital practices, such as antibiotic monotherapy utilising rifampicin-impregnated medical devices, have driven the evolution of this organism, towards potentially incurable infections.

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