Subtle genetic changes enhance virulence of methicillin resistant and sensitive Staphylococcus aureus.
BACKGROUND
Community acquired (CA) methicillin-resistant Staphylococcus aureus (MRSA) increasingly causes disease worldwide. USA300 has emerged as the predominant clone causing superficial and invasive infections in children and adults in the USA. Epidemiological studies suggest that USA300 is more virulent than other CA-MRSA. The genetic determinants that render virulence and dominance to USA300 remain unclear.


RESULTS
We sequenced the genomes of two pediatric USA300 isolates: one CA-MRSA and one CA-methicillin susceptible (MSSA), isolated at Texas Children's Hospital in Houston. DNA sequencing was performed by Sanger dideoxy whole genome shotgun (WGS) and 454 Life Sciences pyrosequencing strategies. The sequence of the USA300 MRSA strain was rigorously annotated. In USA300-MRSA 2658 chromosomal open reading frames were predicted and 3.1 and 27 kilobase (kb) plasmids were identified. USA300-MSSA contained a 20 kb plasmid with some homology to the 27 kb plasmid found in USA300-MRSA. Two regions found in US300-MRSA were absent in USA300-MSSA. One of these carried the arginine deiminase operon that appears to have been acquired from S. epidermidis. The USA300 sequence was aligned with other sequenced S. aureus genomes and regions unique to USA300 MRSA were identified.


CONCLUSIONS
USA300-MRSA is highly similar to other MRSA strains based on whole genome alignments and gene content, indicating that the differences in pathogenesis are due to subtle changes rather than to large-scale acquisition of virulence factor genes. The USA300 Houston isolate differs from another sequenced USA300 strain isolate, derived from a patient in San Francisco, in plasmid content and a number of sequence polymorphisms. Such differences will provide new insights into the evolution of pathogens.
Highlander
Sarah K
SK
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA. sarahh@bcm.edu
Hultén
Kristina G
KG
Qin
Xiang
X
Jiang
Huaiyang
H
Yerrapragada
Shailaja
S
Mason
Edward O
EO
Shang
Yue
Y
Williams
Tiffany M
TM
Fortunov
Régine M
RM
Liu
Yamei
Y
Igboeli
Okezie
O
Petrosino
Joseph
J
Tirumalai
Madhan
M
Uzman
Akif
A
Fox
George E
GE
Cardenas
Ana Maria
AM
Muzny
Donna M
DM
Hemphill
Lisa
L
Ding
Yan
Y
Dugan
Shannon
S
Blyth
Peter R
PR
Buhay
Christian J
CJ
Dinh
Huyen H
HH
Hawes
Alicia C
AC
Holder
Michael
M
Kovar
Christie L
CL
Lee
Sandra L
SL
Liu
Wen
W
Nazareth
Lynne V
LV
Wang
Qiaoyan
Q
Zhou
Jianling
J
Kaplan
Sheldon L
SL
Weinstock
George M
GM
D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001483:Base Sequence; D044404:Genomic Islands / Q000235:genetics; D006801:Humans; D006867:Hydrolases / Q000235:genetics; D016106:Methicillin Resistance; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D016366:Open Reading Frames / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D011110:Polymorphism, Genetic; D013203:Staphylococcal Infections / Q000453:epidemiology*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000235:genetics*; D014481:United States / Q000453:epidemiology
D000900:Anti-Bacterial Agents; D006867:Hydrolases; C019723:arginine deiminase