Phage and bacterial infections

David A. Mullin damullin at MAILHOST.TCS.TULANE.EDU
Wed Feb 19 23:35:29 EST 1997


>Teresa L. Choate wrote:
>> 
>> Hello, I am a senior microbiology major at California State University and I
>> am interesting in phage research.  Particularly, I would like to know if
>> anyone knows of any ongoing or past research concerning the possible use of
>> phage as treatment for bacterial infection.  If anyone has information on
>>this
>> type of research or where I could find this information, it would be greatly
>> appreciated.  Also, if there is any information on why this may be an
>> inplausible idea please let me know...thank you.
>> 
>>    Teresa Choate       ntlbnklr at ix.netcom.com
>
>Patterns of phage resistance and susceptibility have been used for years 
>as a way of differentiating strains within a single species. This tends 
>to suggest that phages are too specific in their mode of attack to be 
>much use in the treatment of infection. You might also consider col 
>factors...
>
>You may also care to look at phages as pathogenic agents - diphtheria and 
>scarlet fever toxins are both phage-coded...
>
>Graham Shepherd
>microHero at compuserve.com


        Dear Teresa,

        I have read a couple of replies to your question that discount the
potential use of phage to treat bacterial infections.  I can tell you that
this is an active area of research that shows great potential.  Much of the
early bacteriophage work concentrated on clinical applications--it was
hoped that bacteriophages would seek out and destroy pathogenic bacteria in
the human body.  This approach was tried on cholera patients in India, but
it did not work well because phage particles were efficiently removed from
the blood by macrophages in liver, spleen and bone marrow, also, the early
phage preparations probably contained lipopolysaccharide and other toxins
released when by cells that were used to produce the phage preps.  Also, at
the time the nature of phage was not known--they thought that all phages
were the same ie. phage could lyse any bacteria and it was not known that
phage were viruses.  In the 1940s the phage approach was abandoned due to
the availability and success of antibiotics like penicillin.
        Now we have to rethink the use of phage because Carl Merril and
Sankar Adhya and colleagues have shown that phage can cure fatal bacterial
infections in mice.  They used highly purified preparations of phage lambda
to cure Escherichia coli blood infections.  In addition, they genetically
selected phage mutants that survived in the blood stream longer (For a
reference see Proc. Natl. Acad. Sci. USA 93:3189).  This approach also
worked with a Salmonella typhimurium blood infection using phage P22.  and
investigators are trying Staphylococcus aureus phage and other phages. 
This approach may be therapeutically useful in cases where available
antibiotics do not work.

        Sincerely,


        David Mullin




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