Staphylococcal Superantigens Cause Lethal Pulmonary Disease in Rabbits

Abstract

Background The CDC et al. reported methicillin-resistant S. aureus (MRSA) are significant causes of serious human infections, including pulmonary illnesses. We investigated the role of superantigens (SAgs) in lung-associated lethal illness in rabbits. Methods A rabbit model was established to investigate the potential role of SAgs, staphylococcal enterotoxin (SE) B and SEC, and toxic shock syndrome toxin-1 (TSST-1). Rabbits received intra-bronchial community-associated (CA) MRSA strains USA200 (TSST-1+), MW2 (SEC+), or c99-529 (SEB+), or purified SAgs. Some rabbits were pre-immunized against SAgs or treated with soluble high-affinity T cell receptors (Vβ-TCR) to neutralize SEB and then challenged intra-bronchially with CA-MRSA or SAgs. Results Rabbits challenged with CA-MRSA or SAgs developed fatal, pulmonary illnesses. Animals pre-immunized against purified SAgs, or treated passively with Vβ-TCRs, and then challenged with CA-MRSA or SAgs, survived. Lung histology indicated non-immune animals developed lesions consistent with necrotizing pneumonia after challenge with CA-MRSA or purified SAgs. SAg immune animals or animals treated with soluble Vβ-TCRs did not develop pulmonary lesions. Conclusions SAgs contribute to lethal pulmonary illneses due to CA-MRSA; pre-existing immunity to SAgs prevents lethality. Administration of high-affinity Vβ-TCR with specificity for SEB to non-immune animals protects from lethal pulmonary illness due to SEB+ CA-MRSA and SEB.

Biofilm formation of Brazilian meticillin-resistant Staphylococcus aureus strains: prevalence of biofilm determinants and clonal profiles

“…Recent research has shown that antibiotic resistance, production of enzymes and toxins, ability to form biofilm and evasion of the immune system are key factors that contribute to the global spread of S. aureus (Chambers & Deleo, 2009;Schlievert et al, 2010;Strandberg et al, 2010;Foster et al, 2014).…”

Staphylococcal and Streptococcal Superantigen Exotoxins

“…It is important to remember that mice are highly resistant to superantigens unless the liver is damaged first with D-galactosamine (230), which causes liver necrosis, a feature not seen in cases of human TSS. Additionally, superantigens cause lethal TSS in rabbits as applied intrapulmonarily (231). Studies with the use of isogenic strains that differ only in production of superantigens (232) and the use of active and passive immunization against specific superantigens to protect rabbits (44,134,231) conclusively establish that superantigens cause TSS.…”

Interference of the T Cell and Antigen-Presenting Cell Costimulatory Pathway Using CTLA4-Ig (Abatacept) Prevents Staphylococcal Enterotoxin B Pathology

“…SEB is the superantigen commonly associated with staphylococcal food poisoning, but it can also cause widespread systemic damage and toxic shock syndrome (3,4). The toxin has been shown to cause lethal pulmonary disease and contribute to pneumonia in vivo (5)(6)(7). SEB is stable to aerosolization, and inhalation of small amounts can cause severe lung pathology, shock, and death (4)(5)(6)(7).…”

“…The toxin has been shown to cause lethal pulmonary disease and contribute to pneumonia in vivo (5)(6)(7). SEB is stable to aerosolization, and inhalation of small amounts can cause severe lung pathology, shock, and death (4)(5)(6)(7).…”