5. ANTIBIOSIS AND ANTIBIOTICS
277
103b), or rather a wall-deficient spheroplast (104), sometimes capable
of growth (105a).
This mode of action (105b) is similar to that observed in the case
not only of other antibiotics such as novobiocin, D-cycloserine, bacitracin
(106), vancomycin (107a,b), but also with other chemicals such as a
particular sample of gentian violet (108), D-amino acids acting at low
concentration (109, 110), L-amino acids, especially glycine and serine, at
half molar or higher concentration (111, 112), uracil analogs
(113-115),
and even lithium chloride (116a) or potassium tellurite (116b).*
However, the precise step that is inhibited and the mechanism of
inhibition are certainly different in each case. Alanine incorporation into
the basal mucopeptide of the cell wall is prevented by D-cycloserine
(60, 71a, 117-120a). The penicillins, possibly on account of a structural
similarity (120b), appear to inhibit the transglycosidation thanks to
which the N-acetylmuramic acid peptide is transferred from its uridine
nucleotide to its definitive site in the cell wall, as shown by the accumulation of such nucleotides in penicillin-inhibited cultures (97,
121-123e).
Similarly, the accumulation, in penicillin-treated staphylococcal cultures,
of ribitol-containing cytidine nucleotides suggests that incorporation of
ribitol into the teichoic acids of the cell wall is also inhibited by the
antibiotic (124, 125).
Gentian violet prevents the addition to N-acetylmuramic acid nucleotide of the first amino acid of the peptide L-alanine (108). The site of
action of amino acids remains uncertain, but it should be stressed that if
glycine at molar concentration has no dissolving action on isolated cell
walls (126), it nevertheless lyses (127) or, in the presence of a stabilizer
such as 20% sucrose, converts into spheroplasts (111), the cells of resting
but not of heat-killed bacterial suspensions. Its action is, however, much
more pronounced on growing cells (128, 129). Uracil analogs act very
likely as specific antagonists of uracil, and possibly of cytidine, which are
part of the transferring coenzymes. Finally, it should be recalled that
bacteriolysis or conversion into spheroplasts is also observed when suitable bacteria are so placed that they lack a specific growth factor indis* Lysis of gram-negative rods by SH-binding and oxidizing agents, but not by
reducing substances, was recently reported. The residue is made up of impure cell
walls. Treated cells are protected by a high osmotic pressure. The reagents have no
visible effect on isolated cell walls or cytoplasmic membranes. Lysis is explained by
an alteration of the cell envelopes, but whether it is a direct action, to be compared
to that of lysozyme, or an indirect one of the same kind as that of penicillin, is left as
an open question [M. Schaechter and K. A. Santomassino, /. Bacteriol. 84, 318-325
(1962)].
277
103b), or rather a wall-deficient spheroplast (104), sometimes capable
of growth (105a).
This mode of action (105b) is similar to that observed in the case
not only of other antibiotics such as novobiocin, D-cycloserine, bacitracin
(106), vancomycin (107a,b), but also with other chemicals such as a
particular sample of gentian violet (108), D-amino acids acting at low
concentration (109, 110), L-amino acids, especially glycine and serine, at
half molar or higher concentration (111, 112), uracil analogs
(113-115),
and even lithium chloride (116a) or potassium tellurite (116b).*
However, the precise step that is inhibited and the mechanism of
inhibition are certainly different in each case. Alanine incorporation into
the basal mucopeptide of the cell wall is prevented by D-cycloserine
(60, 71a, 117-120a). The penicillins, possibly on account of a structural
similarity (120b), appear to inhibit the transglycosidation thanks to
which the N-acetylmuramic acid peptide is transferred from its uridine
nucleotide to its definitive site in the cell wall, as shown by the accumulation of such nucleotides in penicillin-inhibited cultures (97,
121-123e).
Similarly, the accumulation, in penicillin-treated staphylococcal cultures,
of ribitol-containing cytidine nucleotides suggests that incorporation of
ribitol into the teichoic acids of the cell wall is also inhibited by the
antibiotic (124, 125).
Gentian violet prevents the addition to N-acetylmuramic acid nucleotide of the first amino acid of the peptide L-alanine (108). The site of
action of amino acids remains uncertain, but it should be stressed that if
glycine at molar concentration has no dissolving action on isolated cell
walls (126), it nevertheless lyses (127) or, in the presence of a stabilizer
such as 20% sucrose, converts into spheroplasts (111), the cells of resting
but not of heat-killed bacterial suspensions. Its action is, however, much
more pronounced on growing cells (128, 129). Uracil analogs act very
likely as specific antagonists of uracil, and possibly of cytidine, which are
part of the transferring coenzymes. Finally, it should be recalled that
bacteriolysis or conversion into spheroplasts is also observed when suitable bacteria are so placed that they lack a specific growth factor indis* Lysis of gram-negative rods by SH-binding and oxidizing agents, but not by
reducing substances, was recently reported. The residue is made up of impure cell
walls. Treated cells are protected by a high osmotic pressure. The reagents have no
visible effect on isolated cell walls or cytoplasmic membranes. Lysis is explained by
an alteration of the cell envelopes, but whether it is a direct action, to be compared
to that of lysozyme, or an indirect one of the same kind as that of penicillin, is left as
an open question [M. Schaechter and K. A. Santomassino, /. Bacteriol. 84, 318-325
(1962)].