Following the first sequencing of S. aureus
), 11 additional S. aureus
genomes have been determined and deposited into the databases. Here we add the whole genome sequence of S. aureus
Newman to this rapidly growing list. Genome sequencing projects for multiple isolates of a bacterial pathogen are of considerable scientific value because the generated data reveal not only gene content but also conservation and variability between different strains and their associated human or animal diseases. Staphylococcal diversity is mainly due to polymorphisms that occur in genomic islands, which also carry many virulence and antibiotic resistance determinants. Nevertheless, some genes, such as the staphylocoagulase gene, are located outside of genomic islands and are known to be polymorphic (32
). One can add to this list certain combinations of virulence genes, for example, seh
(enterotoxin H) and cna
(collagen-binding protein), which are present only in certain types of S. aureus
strains. A hallmark of the S. aureus
classification is the ability of these microbes to ferment mannitol and to produce characteristic proteins such as DNase, coagulase, and protein A. S. aureus
strains differ from one another in virulence and drug resistance features that are carried in or outside of genomic islands.
Previous works (3
) revealed virulence genes or candidate virulence genes within four prophages that have integrated into the genome of S. aureus
Newman. Our determination of the whole genome sequence for strain Newman showed that many virulence-related genes are encoded by prophages. One superantigen, staphylococcal enterotoxin A (sea
), is located in
NM3; however, unlike other staphylococcal strains, additional superantigen genes were not found. Furthermore, S. aureus
Newman carries a small pathogenicity island but lacks known virulence genes. We also failed to identify the collagen adhesin gene that is present in strains MW2, MRSA252, and MSSA476. Therefore, it is likely that virulence caused by strain Newman largely relies on prophages, in addition to the contribution by other virulence determinants present in all S. aureus
strains, and the nonprophage regions of strain Newman genome seem to form the basic backbone of pathogenic S. aureus
. While en bloc transfer of virulence genes via prophages and pathogenicity islands appears to be important for S. aureus
acquisition of virulence properties, stepwise incorporation of additional genes and/or mutations may play an additional role in the evolution of clones with similar, yet discretely different strategies for the pathogenesis of human disease.
As shown in Fig. , analysis of two major pathogenicity islands in 12 different S. aureus
genome sequences revealed that these strains do not always share the same combinations of νSaα and νSaβ classes. Moreover, the classes do not correlate with phylogenic relationship based on the allelic distribution of seven housekeeping genes upon MLST analysis (7
). This clearly shows that these two pathogenicity islands were horizontally acquired and must have evolved independently of S. aureus
genomes, whereas housekeeping genes are considered to evolve in a vertical fashion. Interestingly, sequences of hsdS
gene products that determine the site specificity of methylation and restriction in restriction-modification systems vary depending on the type of pathogenicity islands that encodes them. The reasons why modification subunits of the R-M system are present in νSaα and νSaβ and have sequence variations remain unknown. One possible explanation is that sequence diversity in pathogenicity islands requires its distinct restriction modification site determined by HsdS: since self-DNA protection by modification system is promoted by sequence-specific methylation on DNA, sequence diversity in genomic islands should coincide with the methylation site determined by HsdS. DNA methylation of pathogenicity islands may further influence expression of the virulence gene and thereby affect the pathogenesis of infectious diseases caused by this organism. Recent studies have revealed that type I RM system activity and modification site specificity are related to changes in the surface antigenic protein in Mycoplasma pulmonis
, depending on the organism's infection sites (12
). This suggests that the RM system in S. aureus
also plays a direct role in virulence.
Some of the genes located within the major pathogenicity islands, νSaα and νSaβ, are presumed to be involved in virulence. However, their molecular contributions to pathogenicity are still unclear. It should also be noted that the presence of any one gene does not result in its expression. In order to reveal the mechanisms of virulence further, microarray experiments could be used to reveal their expression.
The overall spectrum and individual combinations of virulence genes, as they are diversely encoded by different genomic islands, appears to be the major factor in determining clinical symptoms after S. aureus
infection and may even dictate the severity of diseases caused by this pathogen. Together with an analysis of transposon insertion mutants (4
), our work here may provide experimental strategies for better understanding the pathogenicity and physiology of S. aureus