Would bacteriophages kill resistant bacteria?

Michael Benedik benedik at uh.edu
Thu Mar 28 10:40:27 EST 1996

In article <17757C26FS86.PATH4 at TIFTON.CPES.PEACHNET.EDU>
path4 at tifton.cpes.peachnet.edu writes:

> >The idea of using phage as an antimicrobial agent has been around since
> >nearly the turn of the century. The problem is that resitance to phage
> >tends to arise quite easily. Usually just a simple knockout mutation in
> >the phage receptor. So phage resistant things would be expect to arise
> >rapidly.
> >
> >Second problem is that most phage are pretty highly strain specific,
> >many phage of  E. coli K12 for example won't grow well in E. coli C or
> >B strains (some do, some don't). Also you have restriction problem. Not
> >all  E. coli strains have same restriction system, and the same is
> >certainly going to be true for lots of other bacteria. So in order for
> >this to really work well you would need to purify the resistant
> >bacteria and find appropriate phage to propagate on it (and you would
> >probably need multiple phages, not just one, to circumvent the phage
> >resistance problem). I think the whole procedure would end up taking
> >longer than the course of the infection.
> >Michael Benedik
> >Department of Biochemical Sciences
> >University of Houston
> >benedik at uh.edu
> Phage treatments have been evaluated for the control of plant diseases
> caused by bacteria.  In addition to the ratio of phage to bacterial
> cells required, the growth phase of the bacterium is also a determining
> factor in infection and lysis.  As an example, the spot method on an agar
> overlay resulting in a lytic zone produced by the phage is restricted to
> a relatively small diameter because the bacteria become insensitive in
> later stages of growth.  If not, the phage should eventually lyse all
> cells and clear the entire plate.  This does not happen.  Also, if I'm not
> mistaken the dynamics of attachment and infection by phage with a susceptible
> bacterium is affected by the growth medium and if it is on a solid surface
> such as agar or in a liquid suspension?  Perhaps someone with more knowledge
> about phage could verify or refute this information.
> R.D. Gitaitis
> Dept. of Plant Pathology
> Coastal Plain Experiment Station
> University of Georgia
> Tifton, GA

What you state is partly true, it really depends upon the phage. For
example you cite the observation that phage plaques don't take over the
entire plate. This is correct for most phages (but not all, some of the
T phages of e. coli will overgrow and entire plate). It really is phage
specific and depends I assume on whether the phage is capable of
replicating in non=replicating cells or not. But you are correct in
that MOST phages will likely not replicate in non-growing (stationary
phase or starved) cells. 

Likewise you can't make general statements about attachement and
infectivity,it is very phage dependent. Some receptors are media
controlled (lamB controlled by maltose for lambda, although there is
generally enough around even without maltose) and others which are not
obviously media controlled. 

So the bottom line is that everything is phage/bacterium specific and
it is hard to make any general system work for everything.

Michael Benedik
Department of Biochemical Sciences
University of Houston
benedik at uh.edu

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