Distinctive patterns in the human antibody response to Staphylococcus aureus bacteremia in carriers and non‐carriers

Abstract

Staphylococcus aureus is both a prominent cause of nosocomial infections with significant morbidity and mortality and a commensal with nasal carriage in around 30% of the population. The rapid spread of multi-resistant strains necessitates novel therapeutic strategies, a challenging task because the species S. aureus and the host response against it are highly variable. In a prospective study among 2023 surgical and non-surgical patients, 12 patients developed S. aureus bacteremia. They were analysed in detail using a personalized approach. For each patient, the extracellular proteins of the infecting S. aureus strain were identified and the developing antibody response was assessed on 2-D immunoblots. S. aureus carriers showed clear evidence of strain-specific pre-immunization. In all immune-competent bacteremia patients, antibody binding increased strongly, in most cases already at diagnosis. In endogenous infections, the pattern of antibody binding was similar to the pre-infection pattern. In exogenous infections, in contrast, the pre-infection pattern was radically altered with the acquisition of new specificities. These were characteristic for individual patients. Nevertheless, a common signature of 11 conserved S. aureus proteins, recognized in at least half of the bacteremic patients, was identified. All patients mounted a dynamic antibody response to a subset of these proteins.

Comparative Exoproteomics and Host Inflammatory Response in Staphylococcus aureus Skin and Soft Tissue Infections, Bacteremia, and Subclinical Colonization

“…However, Isd was not shown to be antigenic in all of the patients and controls in our study. This is in agreement with the previous findings of Kolata et al demonstrating that Isd proteins such as IsdH, IsdA, and IsdB could not been identified in bacteremia patients (15). Taken together, these results may help to explain the failure of V710 (vaccine containing IsdB) in clinical trials (64).…”

“…However, most of these studies were carried out with a single strain or infection type with limited follow-up using data on patient serum antibodies. In addition, most of these studies used IPG strips with pHs ranging from 3 to 10 to cover a wide range of proteins or pH 6 to 11, as most of the immunoreactive proteins are resolved in this range (9,15). 2-DGE in a pH range of 3 to 10 displayed a crowded appearance and low resolution of protein spots, especially for pI values between 4 and 7 (31).…”

“…Until now, most staphylococcal immunoproteomic studies have focused mainly on proteins in the pI range of 6 to 11, as this range is known to cover the majority of well-known virulence factors (11,14,15). We investigated exoproteins at lower pI values of 4 to 7 in order to get a clearer picture of all of the proteins involved.…”

Predictors of Mortality in Staphylococcus aureus Bacteremia

“…As antibody levels are shaped during S. aureus colonization prior to infection (146), it is plausible that antibody levels may provide some protection and improve outcomes for these patients. More direct evidence for protective antibody responses was observed in a single-center prospective Swedish study, which detected a significant (P Ͻ 0.05) association between 28-day mortality and low levels of antibodies to teichoic acid (relative risk [RR], 4.1; 95% CI, 1.3 to 13.3), lipase (RR, 4.3; 95% CI, 1.3 to 13.1), enterotoxin A (RR, 3.6; 95% CI, 1.1 to 11.9), and scalded skin syndrome toxin (RR, 13.2; 95% CI, 1.7 to 99.7) (118).…”

“…Given the impact of SAB, humoral responses warrant further study, which in turn may enable better vaccination strategies (118,146,306).…”