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MAURICE WELSCH
It follows that the fundamental reasons why each antibiotic displays
a characteristic spectrum of action remain generally poorly understood.
Broadly speaking, natural resistance may be due to: (a) inactivation of
the antibiotic—the penicillino-resistance of species or strains producing
penicillinase is a case in point; (b) nonpenetration of the antibiotic into
the cell or inability to reach the sensitive receptor; (c) absence from,
or nonessentiality for, the cell of the specifically sensitive biochemical
system.
Similarly, the biochemical variations primarily responsible for the
specific acquisition of resistance to an antibiotic remain, on the whole,
obscure although numerous biochemical differences have been reported
between a sensitive mother strain and the derived resistant ones. On the
contrary, the genetic aspect of the problem has progressed more satisfactorily. The occurrence of spontaneous mutation followed by selection
is now an experimentally established fact, and the main assumptions
required by the theory—variation of resistance by discontinuous steps
and polygenic control of resistance—have been corroborated by direct
transformation, transduction, and recombination experiments (20-23).
Much remains to be done, however, before one could hope to propose fundamental correlations either between the mode and specificity
of action of antibiotics on the one hand, their chemical nature on the
other, or between the sensitivity of cells to antibiotics and their biochemical structures and activities.
2. Biosynthesis of Antibiotics
A first problem of interest is the production of antibiotics in relation
to taxonomy. Unfortunately, the search for antibiotics has been conducted quite unevenly among different groups of organisms. Relatively
little is known of "animal" antibiotics, from which we exclude the antimicrobial agents generally studied by the immunologist. Although antibiotics have been extracted in great number from higher plants and
large fungi, comparatively few of them have been chemically identified
and studied. Even among microorganisms, some groups, for instance the
actinomycetes and the bacilli, have been much more thoroughly explored
than others and, on the whole, the antibiotics which they have yielded
have been more adequately and minutely studied. But such a situation
is not necessarily an indication that antibiotic production by actinomycetes or bacilli is more frequent than by other bacteria, by fungi, by
higher plants, or by animals, but rather that the former organisms have
thus far given more useful antibiotics than the latter.
The information available is thus so biased that any generalization
MAURICE WELSCH
It follows that the fundamental reasons why each antibiotic displays
a characteristic spectrum of action remain generally poorly understood.
Broadly speaking, natural resistance may be due to: (a) inactivation of
the antibiotic—the penicillino-resistance of species or strains producing
penicillinase is a case in point; (b) nonpenetration of the antibiotic into
the cell or inability to reach the sensitive receptor; (c) absence from,
or nonessentiality for, the cell of the specifically sensitive biochemical
system.
Similarly, the biochemical variations primarily responsible for the
specific acquisition of resistance to an antibiotic remain, on the whole,
obscure although numerous biochemical differences have been reported
between a sensitive mother strain and the derived resistant ones. On the
contrary, the genetic aspect of the problem has progressed more satisfactorily. The occurrence of spontaneous mutation followed by selection
is now an experimentally established fact, and the main assumptions
required by the theory—variation of resistance by discontinuous steps
and polygenic control of resistance—have been corroborated by direct
transformation, transduction, and recombination experiments (20-23).
Much remains to be done, however, before one could hope to propose fundamental correlations either between the mode and specificity
of action of antibiotics on the one hand, their chemical nature on the
other, or between the sensitivity of cells to antibiotics and their biochemical structures and activities.
2. Biosynthesis of Antibiotics
A first problem of interest is the production of antibiotics in relation
to taxonomy. Unfortunately, the search for antibiotics has been conducted quite unevenly among different groups of organisms. Relatively
little is known of "animal" antibiotics, from which we exclude the antimicrobial agents generally studied by the immunologist. Although antibiotics have been extracted in great number from higher plants and
large fungi, comparatively few of them have been chemically identified
and studied. Even among microorganisms, some groups, for instance the
actinomycetes and the bacilli, have been much more thoroughly explored
than others and, on the whole, the antibiotics which they have yielded
have been more adequately and minutely studied. But such a situation
is not necessarily an indication that antibiotic production by actinomycetes or bacilli is more frequent than by other bacteria, by fungi, by
higher plants, or by animals, but rather that the former organisms have
thus far given more useful antibiotics than the latter.
The information available is thus so biased that any generalization