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

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.Community acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are increasing worldwide [1,2]. Although the emergence is concurrent, genetically distinct clones have been reported from different continents [3-6]. In the United States, two clones, USA300 and USA400 have been associated with the majority of CA-MRSA infections [7]. However, USA300 is currently being reported as the predominant cause of both adult and pediatric CA-MRSA infections in many states [8-12]. At Texas Children's Hospital (TCH) in Houston, Texas, we have observed a continuous increase of CA-S. aureus infections, predominantly CA-MRSA, in a