Inhibitory effects of soluble MD-2 and soluble CD14 on bacterial growth

The effects of the soluble forms of the endotoxin receptor molecules sMD-2 and sCD14 on bacterial growth were studied. When Escherichia coli and Bacillus subtilis were incubated at 37 degrees C for 18 hr with either sMD-2 or sCD14, growth of these bacteria was significantly inhibited as evaluated by viable cell counts and NADPH/NADH activity. A mutant of sCD14 (sCD14d57-64) lacking a region essential for LPS binding did not inhibit the growth of E. coli, whereas this mutant did inhibit the growth of B. subtilis. Addition of excess PG to the bacterial culture reversed the inhibitory effect of sMD-2 on the growth of B. subtilis, but not on the growth of E. coli. Furthermore, when evaluated by ELISA, both sMD-2 and sCD14 bound specifically to PG. Taken together, these results indicate that sMD-2 and sCD14 inhibit the growth of both Gram-positive and Gram-negative bacteria and further suggest that binding to PG and LPS is involved in the inhibitory effect of sMD-2 on Gram-positive bacteria and of sCD14 on Gram-negative bacteria, respectively.