Prevalence of Staphylococcus aureus protein A (spa) mutants in the community and hospitals in Oxfordshire

Abstract

BackgroundStaphylococcal protein A (spa) is an important virulence factor which enables Staphylococcus aureus to evade host immune responses. Genotypes known as “spa-types”, based on highly variable Xr region sequences of the spa-gene, are frequently used to classify strains. A weakness of current spa-typing primers is that rearrangements in the IgG-binding region of the gene cause 1-2% of strains to be designated as “non-typeable”.ResultsWe developed an improved primer which enabled sequencing of all strains, containing any type of genetic rearrangement, in a large study among community carriers and hospital inpatients in Oxfordshire, UK (6110 isolates). We identified eight novel spa-gene variants, plus one previously described. Three of these rearrangements would be designated “non-typeable” using current spa-typing methods; they occurred in 1.8% (72/3905) asymptomatically carried and 0.6% (14/2205) inpatient S. aureus strains. Some individuals were simultaneously colonized by both formerly non-typeable and typeable strains; previously such patients would have been identified as carrying only currently typeable strains, underestimating mixed carriage prevalence and diversity. Formerly non-typeable strains were found in more spa-types associated with multilocus sequence type ST398 (35%), common among livestock, compared to other groups with any non-typeable strains (1-4%), suggesting particular spa-types may have been under-represented in previous human studies.ConclusionsThis improved method allows us to spa-type previously non-typeable strains with rearrangements in the spa-gene and to resolve cases of mixed colonization with deletions in one or more strains, thus accounting for hidden diversity of S. aureus in both community and hospital environments.

Peptidoglycan-linked protein A promotes T cell-dependent antibody expansion duringStaphylococcus aureusinfection

“…Most of these gene rearrangements are in-frame deletions of either the D, B, or C domain coding sequence, resulting in protein A variants with only four IgBDs, similar to that observed for MRSA strain N315 (34). Gene rearrangements with deletions of coding sequence for two, three, or four IgBDs are much more rare (1/6,110) (34). These findings suggest that the IgBD tandem repeats in the spa gene are subject to variation via homologous recombination, as has been observed for other microbial virulence factors with tandem repeat sequences (35,36).…”

“…Rearrangements in the spa gene were observed for IgBD coding sequence in 1.8% of community and 0.6% of hospital isolates (34). Most of these gene rearrangements are in-frame deletions of either the D, B, or C domain coding sequence, resulting in protein A variants with only four IgBDs, similar to that observed for MRSA strain N315 (34). Gene rearrangements with deletions of coding sequence for two, three, or four IgBDs are much more rare (1/6,110) (34).…”

“…Analysis of 3,905 community-and 2,205 hospital-associated S. aureus isolates from Oxfordshire, United Kingdom, revealed that all strains carried intact spa ORFs (34). Rearrangements in the spa gene were observed for IgBD coding sequence in 1.8% of community and 0.6% of hospital isolates (34).…”

“…Analysis of 3,905 community-and 2,205 hospital-associated S. aureus isolates from Oxfordshire, United Kingdom, revealed that all strains carried intact spa ORFs (34). Rearrangements in the spa gene were observed for IgBD coding sequence in 1.8% of community and 0.6% of hospital isolates (34). Most of these gene rearrangements are in-frame deletions of either the D, B, or C domain coding sequence, resulting in protein A variants with only four IgBDs, similar to that observed for MRSA strain N315 (34).…”

Silencing of Long Non-Coding RNA NONHSAT009968 Ameliorates the Staphylococcal Protein A-Inhibited Osteogenic Differentiation in Human Bone Mesenchymal Stem Cells

“…However, the inflammation microenvironment of osteomyelitis is known to attenuates the osteogenic differentiation capacity of stem cells and inhibits osteoblastmediated bone formation, leading to a net bone loss [3,4]. Staphylococcus aureus is the most common microorganism recovered from osteomyelitis [5,6]. Staphylococcal protein A (SpA) is an important virulence factor of Staphylococcus aureus [5,6].…”