Inability of toxin inhibitors to neutralize enhanced toxicity caused by bacteria adherent to tissue culture cells

Abstract

Toxicity to Y-1 adrenal mouse cells caused by heat-labile toxin secreted by an enterotoxigenic strain of Escherichia coli (H-10407-p) was 40-fold enhanced in mixtures containing organisms capable of adhering to the Y-1 cells compared with monolayers exposed to organisms whose adherence was inhibited by mannoside. Severalfold the concentrations of anti-heat-labile toxin antibodies required to neutralize the toxicity of nonadherent bacteria were unable to neutralize the toxicity caused by adherent bacteria. The cytolytic activity toward tissue culture cells and mouse peritoneal macrophages caused by streptolysin S carried by Streptococcus pyogenes was severalfold increased in mixtures containing organisms capable of adhering to the target cells compared with mixtures containing nonadherent bacteria. The ability of trypan blue and RNA core to inhibit the cell-bound streptolysin S was determined in tissue culture cells containing adherent streptococci and mixtures of streptococci randomly colliding with erythrocytes. Both inhibitors were markedly less effective in neutralizing cytolysis than in their ability to neutralize hemolysis. We conclude that compared with toxin produced by nonadherent bacteria, those produced by bacteria adherent to cells are targeted more efficiently and become relatively inaccessible to neutralization by toxin inhibitors.