Affiliation:
1. Microbiology Research Unit, Dublin Dental University Hospital, University of Dublin, Trinity College Dublin, Dublin, Ireland
2. National MRSA Reference Laboratory, St. James's Hospital, Dublin, Ireland
3. Department of Clinical Microbiology, School of Medicine, Trinity College Dublin, St. James's Hospital, Dublin, Ireland
4. Institute of Farm Animal Genetics, Friedrich Loeffler Institut, Neustadt-Mariensee, Germany
Abstract
ABSTRACT
Linezolid is often the drug of last resort for serious methicillin-resistant
Staphylococcus aureus
(MRSA) infections. Linezolid resistance is mediated by mutations in 23S rRNA and genes for ribosomal proteins;
cfr
, encoding phenicol, lincosamide, oxazolidinone, pleuromutilin, and streptogramin A (PhLOPS
A
) resistance; its homologue
cfr
(B); or
optrA
, conferring oxazolidinone and phenicol resistance. Linezolid resistance is rare in
S. aureus
, and
cfr
is even rarer. This study investigated the clonality and linezolid resistance mechanisms of two MRSA isolates from patients in separate Irish hospitals. Isolates were subjected to
cfr
PCR, PhLOPS
A
susceptibility testing, 23S rRNA PCR and sequencing, DNA microarray profiling,
spa
typing, pulsed-field gel electrophoresis (PFGE), plasmid curing, and conjugative transfer. Whole-genome sequencing was used for single-nucleotide variant (SNV) analysis, multilocus sequence typing, L protein mutation identification,
cfr
plasmid sequence analysis, and
optrA
and
cfr
(B) detection. Isolates M12/0145 and M13/0401 exhibited linezolid MICs of 64 and 16 mg/liter, respectively, and harbored identical 23S rRNA and L22 mutations, but M12/0145 exhibited the mutation in 2/6 23S rRNA alleles, compared to 1/5 in M13/0401. Both isolates were sequence type 22 MRSA staphylococcal cassette chromosome
mec
type IV (ST22-MRSA-IV)/
spa
type t032 isolates, harbored
cfr
, exhibited the PhLOPS
A
phenotype, and lacked
optrA
and
cfr
(B). They differed by five PFGE bands and 603 SNVs. Isolate M12/0145 harbored
cfr
and
fexA
on a 41-kb conjugative pSCFS3-type plasmid, whereas M13/0401 harbored
cfr
and
lsa
(B) on a novel 27-kb plasmid. This is the first report of
cfr
in the pandemic ST22-MRSA-IV clone. Different
cfr
plasmids and mutations associated with linezolid resistance in genotypically distinct ST22-MRSA-IV isolates highlight that prudent management of linezolid use is essential.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
37 articles.
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