Antibiotics for high G+C ratio Gram Positives

Jim Graham graham at nooospamm.biodec.wustl.edu
Thu Sep 18 11:11:05 EST 1997


Hello Yolande,

Bicycolmycin is a specific inhibitor of the bacterial "Rho" factor, a
part of the transcription termination-antitermination regulatory system.
Essentially all bacteria examined have a "Rho" (~T. Opperman and J. P.
Richardson ~1994), although some high GC forms have unsual variations on
the theme (~Nowatzke and Richardson 1996). However suceptibility to
Bycolmycin varies. Richardson and Nowatzke have characterized effects in
the gram positive Micrococcus luteus. (Mycobacterium leprae and
tuberculosis as well as Streptomyces sp have Rho factors which would
presumably be inhibited by Bicylomycin.

Sponaneous mutants resistant to Bicylomycin (drug distributed only by
research agreement with Fujisawa Japan) have so far only been found in
the ATPase domain of E. coli Rho. As Rho is a very abundant essential
protein, there are some complicated steps necessary to transduce Rho (or
bicyclomycin resistance) mutations. 

As far as I'm aware Bicyclomycin has been around since the 70's at
least, and has never been used in humans. We had presumed toxicity
concerns.

May I ask why you have focued on Bicyclomycin resistance in your
bacterium? "Antibiotic resistance genes" in the context of Bicyclomycin
are alterations in target metabolic processes (much like many
streptomycin resistance markers or pencillin binding proteins.)

Regards,

Jim
J. Graham PhD
Biology Department



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