Characterization of Infecting Strains and Superantigen-Neutralizing Antibodies in Staphylococcus aureus Bacteremia

Abstract

Staphylococcus aureus superantigens (SAgs) are highly potent T cell mitogens. Antibodies against nonenterotoxin gene cluster (non-egc) SAgs are common in healthy adults, whereas neutralizing antibodies against egc SAgs are rare. We investigated the infecting S. aureus strains and the anti-SAg antibody response during S. aureus bacteremia (SAB). This prospective clinical study (www.clinicaltrials.gov, NCT00548002) included 43 injection drug users (IDUs) and 44 group-matched nonaddicts with SAB. spa genotypes and SAg gene patterns (multiplex PCR) of the S. aureus isolates were determined. The neutralizing capacities of sera obtained at the acute phase and the convalescent phase of SAB were tested against the SAg cocktail of the respective infecting strain and a panel of recombinant SAgs. The lineages CC59 and CC30 were more prevalent among bacteremia strains from IDUs than among strains from nonaddicts. SAg gene patterns in isolates from IDUs and nonaddicts were similar. At the acute phase of bacteremia, IDUs had more neutralizing antibodies against non-egc SAgs than did nonaddicts. Antibody titers frequently increased during infection. In contrast, there were no neutralizing antibodies against egc SAgs at disease onset and such antibodies were not induced by SAB. SAB triggers an antibody response only against non-egc SAgs. Preimmunization in IDU patients is probably due to previous exposure to the infecting strain.Staphylococcus aureus is a major human pathogen that causes a wide spectrum of infections, such as toxin-mediated diseases and systemic infections, for instance, bacteremia and endocarditis. At the same time, S. aureus is a commensal that colonizes approximately 35% of the healthy population in the nose (46,48).Among the numerous toxins of S. aureus are the 21 known staphylococcal superantigens (SAgs): the toxic shock syndrome toxin (TSST-1), the staphylococcal enterotoxins (SEA to SEE and SEG to SEJ), and the staphylococcal enterotoxin-like toxins (SElK to SElU) (13,24,33,35,38). They are encoded on mobile genetic elements, like phages and pathogenicity islands (25). SAgs are the causative agents of food poisoning and toxic shock syndrome, but their role in bacteremia is not well defined (13, 28). They can activate a large fraction of T lymphocytes by directly cross-linking certain T cell receptor V␤ domains with conserved structures on major histocompatibility complex class II (MHC II) molecules. This results in a polyclonal T cell activation and massive cytokine release.The more recently described enterotoxin gene cluster (egc) harbors five or six SAg genes (seg, sei, selm, seln, selo, and sometimes selu), which cluster on a staphylococcal pathogenicity island (Sa␤) (17,23). In contrast to the non-egc SAgs, the egc is organized as an operon, and its genes are transcribed into a polycistronic mRNA (17). The egc genes are the most prevalent SAg genes in commensal and invasive S. aureus isolates, with frequencies ranging between 52 and 66% (4, 9, 14).

Superantigens Subvert the Neutrophil Response To Promote Abscess Formation and Enhance Staphylococcus aureus SurvivalIn Vivo

“…Indeed, an inability to form neutralizing antibodies has been linked to many cases of TSS (11,79); however, SAgs also are highly immunogenic, and the majority of the population is able to form both anti-SAg and anti-staphylococcal antibodies (80). Although purified SAgs have long been shown to induce T cell anergy (81)(82)(83)(84), to our knowledge, the role of SAg-mediated T cell anergy has not been demonstrated during a live infection.…”

Low mortality but increasing incidence of Staphylococcus aureus endocarditis in people who inject drugs

“…This might possibly offer some protection and contribute to the more favorable outcome. [35] Finally, transmission of S aureus strains can occur within drug-use networks, [36] and PWID with SAE might thus be colonized and infected with less pathogenic S aureus strains associated with a better outcome. The proportion of severe infections, as well as our 35% left-sided cases, however, appears to belie this.…”

Molecular Epidemiology of Staphylococcus aureus in the General Population in Northeast Germany: Results of the Study of Health in Pomerania (SHIP-TREND-0)

“…Multiplex PCRs were applied for the detection of genes for staphylococcal enterotoxins ( sea to selu ), toxic shock syndrome toxin 1 ( tst ), exfoliative toxins ( eta and etd ), and agr groups 1 to 4, as previously reported (12, 23). …”