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Open Access Highly Accessed Research article

Subtle genetic changes enhance virulence of methicillin resistant and sensitive Staphylococcus aureus

Sarah K Highlander13*, Kristina G Hultén2, Xiang Qin3, Huaiyang Jiang3, Shailaja Yerrapragada3, Edward O Mason2, Yue Shang3, Tiffany M Williams3, Régine M Fortunov2, Yamei Liu6, Okezie Igboeli3, Joseph Petrosino1, Madhan Tirumalai6, Akif Uzman5, George E Fox6, Ana Maria Cardenas1, Donna M Muzny3, Lisa Hemphill3, Yan Ding3, Shannon Dugan3, Peter R Blyth3, Christian J Buhay3, Huyen H Dinh3, Alicia C Hawes3, Michael Holder3, Christie L Kovar3, Sandra L Lee3, Wen Liu3, Lynne V Nazareth3, Qiaoyan Wang3, Jianling Zhou3, Sheldon L Kaplan2 and George M Weinstock134

Author Affiliations

1 Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA

2 Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, TX, USA

3 Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA

4 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA

5 University of Houston-Downtown, Houston, TX, USA

6 University of Houston, Houston, TX, USA

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BMC Microbiology 2007, 7:99  doi:10.1186/1471-2180-7-99

Published: 6 November 2007



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.


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.


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.