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Subject: Re: darwinian medicine
From: ogston at hobbes.kzoo.edu (Walter Ogston) at INTERNETMAIL
Date: 10/13/95 2:20 PM
Shan Putnam (sputnam at tbf.com) writes:
>>> I just finished reading Dr. Stuart Levy's book "The Antibiotic
>> Paradox" and he addresses this very issue (p 245-246).
>> Apparently the literature doesn't support the "remove the
>> antibiotic -- lose the resistance." He states "Since this
>> perstistence is not associated with the constant presence of an
>> antibiotic, it presumably relates to other features of the
>> resistance phenomenon." ie.) antibiotic resistance determinants
>> (whether plasmid mediatated or chromosomal) participating in
>> heavy metal resistance.
Walter Ogston replied:
> I won't argue with the observation that antibiotic resistance
> genes persist in the absence of apparent selection. The
> question is how long? The life time of an unselected gene based
> on the approximately known mutation rates for bacterial DNA
> replication must be thousands of generations or more (I haven't
> done the calculation, I am guessing, so don't flame me if I am
> out by orders of magnitude). How long were the experiments
> cited by Levy carried on for.
> The other possibility, that the same genes are pleiotropic and
> code for heavy metal resistance is interesting. Is there any
> evidence for it? And in the experiments or natural observations
> is selection by heavy metals known to operate?
Perhaps some historic perspective is needed. Penicillin was far from the first
antibacterial agent employed in antimicrobial chemotherapy. Syphilis, caused by
the spirochete Treponema pallidum, was originally treated with mercury. Since
mercury was quite toxic Paul Ehrlich sought an agent to replace it, his 606th
compound tested, Dr. Ehrlich's magic bullet, was Salvarsan (arsphenamine) an
arsenic compound, this was used until the advent of penicillin was effectively
used.
It is interesting that there is a very common plasmid in Staphylococcus aureus
called pI258 which encodes resistance to penicillin, arsenical compounds and
mercury (not to mention cadium and erythromycin). This plasmid is, in part, a
collection of transposons, Tn552 carries the pencillin resistance genes and
Tn551 carries the erthromycin resistance determinant. The presence of any of
the above agents in the environment of the bacterium selects for strains which
carry this plasmid.
As for the question of mutation rates and the numbers of generations of non-
selective growth a bacteria may be subject to prior to encountering an
antimicrobial agent: bacteria in their natural environments do not grow
exponentially in the main (they lead lives of quiet desperation) they are not
rapidly dividing. So relatively few generations elapse when the bacterium is
transferred from one host to another - a rapid burst of growth may ensue when
some new source of nutrients is encountered (at the right temperature) but then
after 20 or so generations the bacterium is back to square one.
Steve Projan
Wyeth-Ayerst Research
