Abstract

BackgroundS. 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.ResultsThese 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.ConclusionSurface 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.

Highlights

  • S. aureus is a coloniser and pathogen of humans and mammals

  • Some of the remaining 16 genes were absent from a small number of S. aureus genomes whilst others were absent from the majority of S. aureus genomes (Additonal file 1 Table S1)

  • Our analysis proves that variation in genes encoding surface proteins is lineage specific, but that many domain variants are conserved across unrelated lineages

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Summary

Introduction

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. S. aureus colonises a range of mammals, including companion animals such as dogs, cats and horses, and livestock such as cows, pigs and goats. It can colonise birds such as chickens and turkeys. Of further concern is the presence of MRSA strains in a variety of animals such as cats, dogs, horses, cows, pigs, chickens and rats [3,4,5,6,7] These animals may act as important reservoirs for human colonisation as is the case for MRSA sequence type (ST)398 that colonises pigs. Vaccines for preventing S. aureus infection in livestock and/or humans would be useful, but commercial livestock vaccines and human clinical trails have so far proved disappointing

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