Complete genomes of two clinical Staphylococcus aureus strains: evidence for the rapid evolution of virulence and drug resistance.
Staphylococcus aureus is an important nosocomial and community-acquired pathogen. Its genetic plasticity has facilitated the evolution of many virulent and drug-resistant strains, presenting a major and constantly changing clinical challenge. We sequenced the approximately 2.8-Mbp genomes of two disease-causing S. aureus strains isolated from distinct clinical settings: a recent hospital-acquired representative of the epidemic methicillin-resistant S. aureus EMRSA-16 clone (MRSA252), a clinically important and globally prevalent lineage; and a representative of an invasive community-acquired methicillin-susceptible S. aureus clone (MSSA476). A comparative-genomics approach was used to explore the mechanisms of evolution of clinically important S. aureus genomes and to identify regions affecting virulence and drug resistance. The genome sequences of MRSA252 and MSSA476 have a well conserved core region but differ markedly in their accessory genetic elements. MRSA252 is the most genetically diverse S. aureus strain sequenced to date: approximately 6% of the genome is novel compared with other published genomes, and it contains several unique genetic elements. MSSA476 is methicillin-susceptible, but it contains a novel Staphylococcal chromosomal cassette (SCC) mec-like element (designated SCC(476)), which is integrated at the same site on the chromosome as SCCmec elements in MRSA strains but encodes a putative fusidic acid resistance protein. The crucial role that accessory elements play in the rapid evolution of S. aureus is clearly illustrated by comparing the MSSA476 genome with that of an extremely closely related MRSA community-acquired strain; the differential distribution of large mobile elements carrying virulence and drug-resistance determinants may be responsible for the clinically important phenotypic differences in these strains.
Holden
Matthew T G
MT
The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom.
Feil
Edward J
EJ
Lindsay
Jodi A
JA
Peacock
Sharon J
SJ
Day
Nicholas P J
NP
Enright
Mark C
MC
Foster
Tim J
TJ
Moore
Catrin E
CE
Hurst
Laurence
L
Atkin
Rebecca
R
Barron
Andrew
A
Bason
Nathalie
N
Bentley
Stephen D
SD
Chillingworth
Carol
C
Chillingworth
Tracey
T
Churcher
Carol
C
Clark
Louise
L
Corton
Craig
C
Cronin
Ann
A
Doggett
Jon
J
Dowd
Linda
L
Feltwell
Theresa
T
Hance
Zahra
Z
Harris
Barbara
B
Hauser
Heidi
H
Holroyd
Simon
S
Jagels
Kay
K
James
Keith D
KD
Lennard
Nicola
N
Line
Alexandra
A
Mayes
Rebecca
R
Moule
Sharon
S
Mungall
Karen
K
Ormond
Douglas
D
Quail
Michael A
MA
Rabbinowitsch
Ester
E
Rutherford
Kim
K
Sanders
Mandy
M
Sharp
Sarah
S
Simmonds
Mark
M
Stevens
Kim
K
Whitehead
Sally
S
Barrell
Bart G
BG
Spratt
Brian G
BG
Parkhill
Julian
J
D024881:Drug Resistance, Bacterial / Q000187:drug effects / Q000235:genetics*; D019143:Evolution, Molecular; D005798:Genes, Bacterial / Q000235:genetics; D014644:Genetic Variation; D016680:Genome, Bacterial; D023281:Genomics; D006801:Humans; D010802:Phylogeny; D017422:Sequence Analysis, DNA; D013203:Staphylococcal Infections / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000145:classification / Q000187:drug effects / Q000235:genetics* / Q000472:pathogenicity*; D014774:Virulence / Q000235:genetics