Yet, S. aureus surface proteins are currently in human vaccine trials. Humans are exposed to a variety of S. aureus lineages. This paper clearly shows that S. aureus populations carry a range of unique variants of surface proteins. Therefore, Volasertib chemical structure animals in vaccine trials should be challenged with a range

of S. aureus lineages so that the vaccine is tested with a representative range of S. aureus surface proteins. If the vaccine is protective against a range of strains, it may then be suitable for human trials. Vaccines cocktails of multiple surface proteins have been tested in animals [27]. However, these also use the variants found in only one laboratory lineage. To obtain good coverage, multiple variants of multiple C646 purchase targets in the vaccine cocktail will likely be more effective. The lack of variant antigens in the vaccines currently tested in animals, humans and livestock may explain their failure to protect from infection with naturally occurring S. aureus populations in the non-laboratory environment. We note that MRSA strains in our collection typically had the same surface and secreted protein profiles as methicillin-sensitive Staphylococcus

aureus (MSSA) from the same lineage. We did not find a surface or secreted Fer-1 cost immune marker of MRSA, nor of HA-MRSA or CA-MRSA strains. If a surface protein is dispensable in some lineages that are still able to cause disease, then its role in virulence is called into question. Many surface proteins appear to bind multiple host proteins, and multiple surface proteins may bind the same host protein [9]. Therefore, the role of individual proteins in disease is difficult to prove and it seems likely that a combination of proteins is essential for virulence.

Intriguingly, some lineages are thought to be more associated with particular human hosts than others [37]. We can show there are subtle variations in the genetic sequences of human host proteins, especially in binding regions, which may be implicated in this host specificity. GBA3 Unexpectedly, the sequences of the animal lineages of S. aureus do not support this hypothesis. If animal strains of S. aureus interact with animal host proteins the bacteria would be expected to have animal specific binding proteins or domains. However this is generally not the case, and the animal strains show gene sequences remarkably similar to those found in human strains. No unique surface proteins with an LPxTG anchoring domain could be identified in any of the animal sequencing projects [38]. Yet, the sequence of predicted animal protein targets is substantially different from human counterparts. How do S. aureus strains interact specifically with non-human hosts? The importance of individual proteins in host-pathogen interactions is therefore difficult to confirm. One factor that is not taken into account in this study is the possibility of strains acquiring additional genes on mobile genetic elements (MGEs).