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Trends Microbiol. 2006 Jul;14(7):304-12. Epub 2006 Jun 8.

Foundations of antibiotic resistance in bacterial physiology: the mycobacterial paradigm.

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Department of Microbiology and Immunology, Life Sciences Centre, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada.


The intrinsic resistance of Mycobacterium tuberculosis and related pathogens to most common antibiotics limits chemotherapeutic options to treat tuberculosis and other mycobacterial diseases. Resistance has traditionally been attributed to the unusual multi-layer cell envelope that functions as an effective barrier to the penetration of antibiotics. Recent insights into mechanisms that neutralize the toxicity of antibiotics in the cytoplasm have revealed systems that function in synergy with the permeability barrier to provide intrinsic resistance. Here, we highlight the growing pool of information about internal, antibiotic-responsive regulatory proteins and corresponding resistance genes, and present new concepts that rationalize how they might have evolved. Pharmaceutical inhibition of these intrinsic systems could make many previously available antibiotics active against M. tuberculosis.

[Indexed for MEDLINE]

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