Objectives

Methicil
l
in
-
resistant
Staphylococcus aureus
(MRSA) is a leading cause of hospital
-
associated
infection.
Acquired r
esistance is encoded by the
mecA
gene
or its homologue
mecC
but little
is known about the evolutionary dynamics involved in gain and loss of resistance.
The
objective of this study was to
obtain an expanded understanding of
S. aureus
methicilin
resistance
micro
evolution
in vivo
,
by focusing on a single lineage
.

Methods
We compared
the
whole genome sequences
of 231 isolates
from a single epidemic
lineage
(clonal complex CC30 and
spa
-
type t018)
of
S. aureus
that caused an epidemic in the United
Kingdom.

Results
We show that
resistance
to methicillin in this single lineage
was gained on at least two
separate occasions
, one of which led to
a clonal expansion around 1995 presumably caused
by a selective advantage
.
Resistance was however
subsequently
lost
in vivo
by nine
strains
isolated
between 2008
and 201
2
.
We
describe the genetic mechanisms involved in this loss of
40
resistance and
the imperfect relationship between
genotypic and phenotypic resistance
.
Conclusions
The
recent
re
-
emergence of
methicillin
susceptibility
in this epidemic lineage
suggests a
significant fitness cost
of
resistance
and
reduced
selective
advantage following the
introduction
in the mid 2000s
of
MRSA hospital control measures
throughout the United
Kingdom.