Guest guest Posted August 22, 2005 Report Share Posted August 22, 2005 Here are more findings from recent years. Looks like P. aeruginosa is up to something similar to Mtb. The presence of tetracyclines causes wild P. aeruginosa to up-regulate its production of certain multi- drug efflux pumps by ~13 fold: http://www.pubmedcentral.gov/articlerender.fcgi? tool=pubmed & pubmedid=12604529 Similar upregulations by an undetermined, but large fold take place in response to gentamycin and erythromycon: http://www.pubmedcentral.gov/articlerender.fcgi?artid=90052 These pumps are barely expressed at all when the bastards are not looking at antibiotics. Existence of such a system is more easily understandable in this organism than in Mtb because it (tho not necessarily the same strains?) is found in soil where it faces antibiotic producing microorganisms: " Pseudomonas aeruginosa was detected in 24% of the soil samples but in only 0.13% of the vegetable samples from various agricultural areas of California " > 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. Quote Link to comment Share on other sites More sharing options...
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