Genetic variation in Staphylococcus aureus surface and immune evasion genes is lineage associated: implications for vaccine design and host-pathogen interactions

Abstract

Background: S. aureus is a coloniser and pathogen of humans and mammals. Whole genome sequences of 58 strains of S. aureus in the public domain and data from multi-strain microarrays were compared to assess variation in the sequence of proteins known or putatively interacting with host.

Results: These included 24 surface proteins implicated in adhesion (ClfA, ClfB, Cna, Eap, Ebh, EbpS, FnBPA, FnBPB, IsaB, IsdA, IsdB, IsdH, SasB, SasC, SasD, SasF, SasG, SasH, SasK, SdrC, SdrD, SdrE, Spa and SraP) and 13 secreted proteins implicated in immune response evasion (Coa, Ecb, Efb, Emp, EsaC, EsxA, EssC, FLIPr, FLIPr like, Sbi, SCIN-B, SCIN-C, VWbp) located on the stable core genome. Many surface protein genes were missing or truncated, unlike immune evasion genes, and several distinct variants were identified. Domain variants were lineage specific. Unrelated lineages often possess the same sequence variant domains proving that horizontal transfer and recombination has contributed to their evolution. Surprisingly, sequenced strains from four animal S. aureus strains had surface and immune evasion proteins remarkably similar to those found in human strains, yet putative targets of these proteins vary substantially between different hosts. This suggests these proteins are not essential for virulence. However, the most variant protein domains were the putative functional regions and there is biological evidence that variants can be functional, arguing they do play a role.

Conclusion: Surface and immune evasion genes are candidates for S. aureus vaccines, and their distribution and functionality is key. Vaccines should contain cocktails of antigens representing all variants or they will not protect against naturally occurring S. aureus populations.

Figure 1

Microarray analysis. Microarrays show gene variants are conserved across unrelated lineages. Genes are listed in order by name and by their annotated gene number prefixed with the strain that was used as the template for the PCR probe on the microarray (R, MRSA252; N, N315; 8, 8325; M, MW2; U, Mu50). A black box indicates the gene or gene variant is present in that lineage. '*' indicates the genome of a strain from this lineage has been sequenced. '+' indicates ORFs from this lineage are included on the 7 strain microarray. C indicates community associated MRSA were included, and H indicates hospital associated MRSA were included. Strains from the following hosts were included: h, human, b, bovine, e, equine, p, pig. 'v' denotes a PCR product designed to a specific variant region. 'u' indicates variation in gene distribution for that lineage.