INHIBITION OF ENHANCED TOXIN PRODUCTION BY CLOSTRIDIUM-DIFFICILE IN BIOTIN-LIMITED CONDITIONS

Production of toxins A and B by Clostridium difficile is enhanced in a defined medium with biotin-limited conditions. In the present study c ompounds inhibitory to enhanced toxin production by a C. difficile str ain were examined, Increases in biotin concentration from 0.05 nM to 5 0 nM accelerated growth and inhibited enhanced toxin production. Aspar agine, glutamic acid and glutamine (10 mM) showed an effect on growth and toxin production similar to that of biotin, Lysine (10 mM) suppres sed growth and inhibited toxin production. Addition of these toxin-inh ibitory compounds within an incubation period of 2 days inhibited the enhanced toxin production, but later addition showed only slight;inhib ition of toxin production. Amino acids contained in the defined medium under the biotin-limited conditions were actively utilised in the pre sence of the three toxin-inhibitory amino acids, but in the presence o f lysine, amino-acid utilisation was suppressed. Different mechanisms of action of these toxin-inhibitory molecules, which may be divided in to excess biotin, asparagine-glutamic acid-glutamine group, and lysine , are discussed.