darwinian medicine

Wed Oct 18 15:33:58 EST 1995

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 

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

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