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[SANET-MG] cows genetically modified tp produce antibiotic



April 10, 2005
Prof. Joe Cummins
“Cows genetically modified to produce antibiotic”
       Mastitis is a major disease in dairy cattle. The disease is caused by
bacteria that invade the mammary and produce inflammation and cause the
milk to contain pus cells.The disease is caused by three bacteria
Staphylococcus aureus (S. auerius), Escherichia coli and Streptococcus
uberis. Of these  pathogens  S. aurius  is probably  the most difficult
to treat  because the bacterium may cause inflammation before antibiotic
treatment takes effect (1).  Recombinant growth hormone  (poslac)
treatment of milk cows to increase  production  increases mastitis risks
about 25% (2).
       Cows genetically modified to resist intra-mammary S. aureus  infection
were recently developed.  Cows bearing a gene from a bacterium,
Staphlococcus simulans, that specifies an antibiotic , lysostaphin were
constructed. First , construction started with  donor fibroblasts
containing  a gene for a selectable marker specifying  neomycin
resistance, a green flourescent protein and the lysostaphin gene whose
DNA code was modified  so that the antibiotic could be produced in
mammalian cells. In those cells expression of the lysostaphin gene  was
regulated by an ovine beta lactoglobulin promoter. The transformed donor
 fibroblasts were used to clone heifers. The cloned heifers produced
milk rich in lysostaphin and resisted infection by S, aurias. The
transgenic antibiotic containing animals were  more effective in
controlling the infection than was the antibiotic treatment  by
injection because the antibiotic produced in mammary cells  prevented
implantation of the pathogen in mammary cells The authors of the study
believed that they had produced a valuable  tool for resisting  disease
to improve the well being of livestock (3). A commentary accompanying
the original research report  pointed out that the transgenic cattle
resisted  S. auerius  improved resistance to mastitis but that the
transgenic antibiotic  did not inhibit other mastitis pathogens such as
Escherichia coli or Streptococcus uberis. But the commentary  argued
that the transgenic cattle might reduce antibiotic use. since the
commentator believed that less lysostaphin would be required than  if
were delivered after the infection appeared(4).
       Efforts to use gene therapy to deliver lysostaphin genes to the goat
mammary  gland  prove successful in producing antibiotic , however, a
strong immune response to both the lysostaphin  and to the gene therapy
vector  adenovirus made the approach unsuitable for treating mastitis (5).
       There is little doubt that the relatively low level  lysostaphin
produced in transgenic cattle (higher levels were avoided because they
were associated with developmental abnormality) will lead to appearance
of  resistance to the antibiotic among the bacterial pathogens.  A
mechanism of lysostaphin resistance has been  in streptococci  and
horizontal gene transfer between Staphlococci and Streptococci has been
determined (6). A  plasmid born resistance to  lysostaphin was based on
modification of cell wall componesnt (7). Resistance to methicillin was
accompanied by resistance to vancomycin and lysostaphin in S, aurius
taken  from a human blood sample (8). There is little doubt that
resistance to lysostaphin  will appear in transgenic cows and that the
resistance genes will be transferred  horizontally to other pathogens
even those causing human disease.
       Using genetic engineering  and cloning to  solve  a problem heightened
by the use of  a recombinant hormone produced using genetic engineering
 must have seemed like a reasonable research project by the advocates
of genetic engineering. Predictably, the research has led to a
potentially chaotic result that seems to have greatly increased  the
risk to human health. In that regard the research may serve as a
paradigm for the goals of genetic engineering that has unleashed a tool
chest of  genetic tinkering  that seems to be turning  adversity into
disaster. As one might expect the research was undertaken and supported
by the United States Department of Agriculture.
References
1.      Lammers, A, Kruijt ,E, van de Kuijt ,C, Nuijten,P. and  Smith, H.
Identification of Staphylococcus aureus genes expressed during growth in
milk: a useful model for selection of genes important in bovine
mastitis? Microbiology. 2000 ,146 ,981-7
2.      Dohoo ,I, DesCoteaux ,L, Leslie, K, Fredeen ,A, Shewfelt ,W, Preston
,A. and  Dowling P. A meta-analysis review of the effects of recombinant
bovine somatotropin. 2. Effects on animal health, reproductive
performance, and culling. Can J Vet Res. 2003,67,252-64
3.      Wall, R, Powell, A, Paape M,, Kerr,D, Bannerman,D, Pursel,V, Wells
,K, Talbot, N. and Hawk, H. Genetically enhanced cows resist
intramammary Staphylococcus aureus infection Nat Biotechnol. 2005 ,23,445-51
4.      Rainard P. Tackling mastitis in dairy cows  Nat Biotechnol. 2005
;23,430-2
5.Fan ,W, Plaut ,K, Bramley ,A, Barlow ,J, Mischler,S.and Kerr ,D.
Persistency of adenoviral-mediated lysostaphin expression in goat
mammary glands J Dairy Sci. 2004,87,:602-8
6.      Heath Farris M, Heath,L, Heath ,H, LeBlanc,P, Simmonds,R. and
Sloan,G. Expression of the genes for lysostaphin and lysostaphin
resistance in streptococci FEMS Microbiol Lett. 2003 ,228,115-9
7.      DeHart,H,Heath ,H, Heath,L, LeBlanc, P. and Sloan, G. The lysostaphin
endopeptidase resistance gene (epr) specifies modification of
Peptidoglycan cross bridges in Staphylococcus simulans and
Staphylococcus aureus  Appl Environ Microbiol. 1995, 61,1475- 9
8.      Boyle-Vavra ,S, Carey,R. and Daum,R  Development of vancomycin and
lysostaphin resistance in a methicillin-resistant Staphylococcus aureus
isolate. J Antimicrob Chemother. 2001 ,48,617-25

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