new work: mycobacterial multi-drug resistance

[Guest guest]

http://www.pnas.org/cgi/content/abstract/0505446102v1

This looks to be a key factor in Mtb's intrinsic resistance in glass

and in flesh to many drugs.

M. tuberculosis and M. smegmatis have a transcription regulator

which is transcribed 70 fold more in the presence of therapeutic

concentrations of at least some abx.

Deleting the gene for this regulator brought Mtb MICs of several

compounds down up to 32-fold. Several of the genes in the regulon of

interest were efflux pumps. Their upregulation fold during regulon

activation was not addressed.

Deleting the orthologous regulator from some soil-dwelling cousins

of the Mycobacterium genus caused even larger MIC differences, yet

did not alter sensitivity to 23 non-antibiotic toxins.

Apparantly no nonantibiotic toxins were tested on the Mtb regulator

mutants (why?). Mtb, unlike many mycobacteria, is not known outside

the human so it is speculated this equipment may have been preserved

from an ancestor present in the soil. Somtheing would have to

motivate this preservation; perhaps hostile host molecules.

Strangely, although sub- and supra-inhibitory tetracycline both

induced the regulon in wild type Mtb, mutational disablement of the

regulon did not alter the tetracycline MIC.