264
MAURICE WELSCH
cates that dihydrostreptomycin inhibits the transfer of amino acids from
ribonucleic acid (RNA) to protein. However, according to Rosano et al.
(48), streptomycin would interfere with RNA metabolism, with the
result that treated cells excrete 5'-nucleotides. The same observation,
reported by Anand et al. (49), is taken as evidence of damage to the
cytoplasmic membrane, which may be fatal in itself (50a) or allow
the penetration of the antibiotic into the cell with lethal consequences
(50b). However, the leakage observed in streptomycin-treated Escherichia coli was not found, under similar conditions, in Staphylococcus
aureus (Micrococcus pyogenes var. aureus), and the osmotic pressure of
protoplasts from streptomycin-inhibited cells of Escherichia coli and
Bacillus megaterium was not significantly different from that of normal
cells (51a).
The bactericidal effect of streptomycin is much reduced under anaerobic conditions, but nothing indicates that the site of action of the
antibiotic is a system more essential to cells growing aerobically than to
cells growing anaerobically. It rather seems that the uptake of streptomycin is dependent upon aerobic respiration and there is a correlation
between the amount of antibiotic irreversibly bound by the cell and its
sensitivity
(51b).
There is some evidence for the localization of streptomycin sensitivity
in the ribosomes (51c,d), where the antibiotic might interfere with
polypeptide synthesis (51e), possibly by "triggering" a depolymerization
of ribonucleic acid (51f). This effect, which is obtained with low concentrations not only of streptomycin, but also of kanamycin and neomycin, is reversed by higher concentrations of the same antibiotics or by
spermine. The protective action appears to be associated with the
basicity of the substances used and is specifically antagonized by phosphate ions (51g). It seems, however, that ribonucleic acid breakdown is
a secondary rather than a fundamental effect of streptomycin since its
inhibition by magnesium does not simultaneously reverse the bactericidal
action. It has been proposed that streptomycin would interfere with a
function of intracellular magnesium and polyamines necessary to maintain the integrity of ribosomes (51h).
On the basis of observations showing that streptomycin-dependent
mutants and sensitive (but not resistant) cells in the presence of the
antibiotic excrete an excess of valine* and leucine, it has been suggested
* Bragg and Polglase have recently confirmed the excess production of L-valine
by a streptomycin-dependent mutant of Escherichia coli growing aerobically in a
glucose medium. They also found that this organism accumulated lactic acid when
grown in a nitrogen atmosphere [P. D. Bragg and W. J. Polglase, /. Bacteriol. 84,
370-374 (1962)].
MAURICE WELSCH
cates that dihydrostreptomycin inhibits the transfer of amino acids from
ribonucleic acid (RNA) to protein. However, according to Rosano et al.
(48), streptomycin would interfere with RNA metabolism, with the
result that treated cells excrete 5'-nucleotides. The same observation,
reported by Anand et al. (49), is taken as evidence of damage to the
cytoplasmic membrane, which may be fatal in itself (50a) or allow
the penetration of the antibiotic into the cell with lethal consequences
(50b). However, the leakage observed in streptomycin-treated Escherichia coli was not found, under similar conditions, in Staphylococcus
aureus (Micrococcus pyogenes var. aureus), and the osmotic pressure of
protoplasts from streptomycin-inhibited cells of Escherichia coli and
Bacillus megaterium was not significantly different from that of normal
cells (51a).
The bactericidal effect of streptomycin is much reduced under anaerobic conditions, but nothing indicates that the site of action of the
antibiotic is a system more essential to cells growing aerobically than to
cells growing anaerobically. It rather seems that the uptake of streptomycin is dependent upon aerobic respiration and there is a correlation
between the amount of antibiotic irreversibly bound by the cell and its
sensitivity
(51b).
There is some evidence for the localization of streptomycin sensitivity
in the ribosomes (51c,d), where the antibiotic might interfere with
polypeptide synthesis (51e), possibly by "triggering" a depolymerization
of ribonucleic acid (51f). This effect, which is obtained with low concentrations not only of streptomycin, but also of kanamycin and neomycin, is reversed by higher concentrations of the same antibiotics or by
spermine. The protective action appears to be associated with the
basicity of the substances used and is specifically antagonized by phosphate ions (51g). It seems, however, that ribonucleic acid breakdown is
a secondary rather than a fundamental effect of streptomycin since its
inhibition by magnesium does not simultaneously reverse the bactericidal
action. It has been proposed that streptomycin would interfere with a
function of intracellular magnesium and polyamines necessary to maintain the integrity of ribosomes (51h).
On the basis of observations showing that streptomycin-dependent
mutants and sensitive (but not resistant) cells in the presence of the
antibiotic excrete an excess of valine* and leucine, it has been suggested
* Bragg and Polglase have recently confirmed the excess production of L-valine
by a streptomycin-dependent mutant of Escherichia coli growing aerobically in a
glucose medium. They also found that this organism accumulated lactic acid when
grown in a nitrogen atmosphere [P. D. Bragg and W. J. Polglase, /. Bacteriol. 84,
370-374 (1962)].