Drug Resistance

Brian Foley btf at t10.lanl.gov
Wed Dec 24 11:57:32 EST 1997


WRowe0521 wrote:
> 
> I'm interested in the way in which drug resistance 
> affects the subsequent
> reproductive fitness of the resistant organism.
> Can anyone tell me of a documented case of a bacterium 
> or protozoan having been
> almost entirely  eliminated by an effective 
> pharmaceutical, rebounding with a
> resistant type and recapturing  (at first or eventually) 
> its original level of
> fitness (virulence, lethality, or some other criterion). 

	There are thousands of research publications on this
topic.  Searching MedLine
http://www3.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=0
for penicillin resistance
returns 8031 documents and narrowing that search
with beta lactamase
returns 715 documents that contain all 4 words.

	There is no such thing as almost eliminating a bacterial
species from earth with drugs.  It would take millions of pounds
of something like penicillin to dust the land areas of the earth
with penicillin, and even with that, bacteria deep in the soil
or within plants and animals would not be touched.
	Smallpox virus has been virtually eliminated by
vaccination, but this is far different from elimination of
a bacterial or protozoan species with antibiotics.
	
	Drugs aimed at inhibiting bacteria without also killing
the eukaryotic host most often fall into one of two classes:
those that affect the prokaryotic ribosome which is significantly
different from the eukaryotic ribosome (tetracycline falls into
this class) and drugs aimed at disrupting the building of 
the prokaryotic cell wall (penicillin falls into this class).
	Resistance to penicillin is generally carried on a 
plasmid carrying the beta lactamase gene.  This addition of
a small set of genes on a plasmid has no detectable detrimental
effect on the overall "fitness" of the bacteria.  The cost of
producing the beta lactamase enzyme which destroys penicillin
is minimal.



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