Revisiting Coley’s Toxins: Immunogenic Cardiolipins from Streptococcus pyogenes

• DOI: 10.1021/jacs.3c07727
• Publication Date: 2023-09-22T17:02:02Z
• Authors: Yern-Hyerk Shin; Sunghee Bang; Sung-Moo Park; Xiao Ma; Chelsi Cassilly; Daniel Graham; Ramnik Xavier; Jon Clardy
• Keywords: Streptococcus Pyogenes; Lipid A

Coley's toxins, an early and enigmatic form of cancer (immuno)therapy, were based on preparations Streptococcus pyogenes. As part a program to explore bacterial metabolites with immunomodulatory potential, S. pyogenes assayed in cell-based immune assay, single membrane lipid, 18:1/18:0/18:1/18:0 cardiolipin, was identified. Its activity profiled additional cellular assays, which showed it be agonist TLR2–TLR1 signaling pathway 6 μM EC50 robust TNF-α induction. A synthetic analog switched acyl chains had no measurable assays. The identification immunogenic cardiolipin restricted structure–activity profile has implications for regulation, immunotherapy, poststreptococcal autoimmune diseases.