Different mechanisms of insensitivity to the staphylococcin-like peptide Pep 5

Three different mechanisms of insensitivity to the bactericidal membrane disrupting action of the staphylococcin-like peptide Pep 5 were found to occur among certain Gram-positive bacteria. i) The immunity of the producer of Pep 5 Staphylococcus epidermidis 5 was shown to be due to a Pep 5 antagonist, which was excreted along with Pep 5 during growth. The cells were killed by Pep 5 when incubated with high doses exceeding the concentration of the antagonist. ii) Bacillus subtilis W23 produced a protease which cleaved Pep 5 into fragments with greatly reduced bactericidal activity. Like with S. epidermidis 5, cells of B. subtilis were susceptible to the membrane damaging action of the peptide and growth in culture was only possible after inactivation of Pep 5. iii) By prolonged incubation in the presence of Pep 5 resistant mutants of S. cohnii 22 and S. epidermidis 5 Pep 5- could be selected. Their cytoplasmic membrane was not sufficiently disrupted by the peptide to promote active killing, resulting in unhindered growth of these mutants in the presence of high doses (200 AU/ml) of Pep 5.