Lee, Jean Y H; Monk, Ian R; Gonçalves da Silva, Anders; Seemann, Torsten; Chua, Kyra Y L; Kearns, Angela; Hill, Robert; Woodford, Neil; Bartels, Mette D; Strommenger, Birgit; Laurent, Frederic; Dodémont, Magali; Deplano, Ariane; Patel, Robin; Larsen, Anders R; Korman, Tony M; Stinear, Timothy P; Howden, Benjamin P

doi:10.1038/s41564-018-0230-7

Author(s)

Lee, Jean Y H

Monk, Ian R

Gonçalves da Silva, Anders

Seemann, Torsten

Chua, Kyra Y L

Kearns, Angela

Hill, Robert

Woodford, Neil

Bartels, Mette D

Strommenger, Birgit

Laurent, Frederic

Dodémont, Magali

Deplano, Ariane

Patel, Robin

Larsen, Anders R

Korman, Tony M

Stinear, Timothy P

Howden, Benjamin P

Publication Date

2018

Abstract

Staphylococcus epidermidis is a conspicuous member of the human microbiome, widely present on healthy skin. Here we show that S. epidermidis has also evolved to become a formidable nosocomial pathogen. 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. These lineages are resistant to rifampicin through acquisition of specific rpoB mutations that have become fixed in the populations. Analysis of isolates from 96 institutions in 24 countries identified dual D471E and I527M RpoB substitutions to be the most common cause of rifampicin resistance in S. epidermidis, accounting for 86.6% of mutations. Furthermore, we reveal that the D471E and I527M combination occurs almost exclusively in isolates from the ST2 and ST23 lineages. By breaching lineage-specific DNA methylation restriction modification barriers and then performing site-specific mutagenesis, we show that these rpoB mutations not only confer rifampicin resistance, but also reduce susceptibility to the last-line glycopeptide antibiotics, vancomycin and teicoplanin. Our study has uncovered the previously unrecognized international spread of a near pan-drug-resistant opportunistic pathogen, identifiable by a rifampicin-resistant phenotype. It is possible that hospital practices, such as antibiotic monotherapy utilizing rifampicin-impregnated medical devices, have driven the evolution of this organism, once trivialized as a contaminant, towards potentially incurable infections.

Citation

Nature microbiology 2018; 3(10): 1175-1185

Jornal Title

Nature microbiology

OrcId

0000-0001-6046-610X

0000-0002-6155-8353

0000-0003-0150-123X

0000-0003-0237-1473

Link

https://ahro.austin.org.au/austinjspui/handle/1/19518

Title

Global spread of three multidrug-resistant lineages of Staphylococcus epidermidis.

Type of document

Journal Article

Austin Health

Global spread of three multidrug-resistant lineages of Staphylococcus epidermidis.

Files:

Author(s)	Lee, Jean Y H Monk, Ian R Gonçalves da Silva, Anders Seemann, Torsten Chua, Kyra Y L Kearns, Angela Hill, Robert Woodford, Neil Bartels, Mette D Strommenger, Birgit Laurent, Frederic Dodémont, Magali Deplano, Ariane Patel, Robin Larsen, Anders R Korman, Tony M Stinear, Timothy P Howden, Benjamin P
Publication Date	2018
Abstract	Staphylococcus epidermidis is a conspicuous member of the human microbiome, widely present on healthy skin. Here we show that S. epidermidis has also evolved to become a formidable nosocomial pathogen. 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. These lineages are resistant to rifampicin through acquisition of specific rpoB mutations that have become fixed in the populations. Analysis of isolates from 96 institutions in 24 countries identified dual D471E and I527M RpoB substitutions to be the most common cause of rifampicin resistance in S. epidermidis, accounting for 86.6% of mutations. Furthermore, we reveal that the D471E and I527M combination occurs almost exclusively in isolates from the ST2 and ST23 lineages. By breaching lineage-specific DNA methylation restriction modification barriers and then performing site-specific mutagenesis, we show that these rpoB mutations not only confer rifampicin resistance, but also reduce susceptibility to the last-line glycopeptide antibiotics, vancomycin and teicoplanin. Our study has uncovered the previously unrecognized international spread of a near pan-drug-resistant opportunistic pathogen, identifiable by a rifampicin-resistant phenotype. It is possible that hospital practices, such as antibiotic monotherapy utilizing rifampicin-impregnated medical devices, have driven the evolution of this organism, once trivialized as a contaminant, towards potentially incurable infections.
Citation	Nature microbiology 2018; 3(10): 1175-1185
Jornal Title	Nature microbiology
OrcId	0000-0001-6046-610X 0000-0002-6155-8353 0000-0003-0150-123X 0000-0003-0237-1473
Link	https://ahro.austin.org.au/austinjspui/handle/1/19518
Title	Global spread of three multidrug-resistant lineages of Staphylococcus epidermidis.
Type of document	Journal Article