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The MAR Regulon The mar operon is a set of genes on the chromosome of E. coli, Shigella, Salmonella, and other enteric gram-negative infectious disease bacteria. These genes act together to confer survival traits to the host bacterium, including resistance to a wide range of antibiotics as well as non-antibiotic toxic environmental conditions. The mar operon acts like a master switch which controls expression of over 80 other proteins in the cell. When activated, the mar system initiates a number of bacterial defense mechanisms, including processes that alter bacterial cell membranes, leading to decreased permeability to drugs, increased export of drugs, and increased intracellular inactivation of toxic elements, resulting in resistance to a broad range of antibiotics and other toxic substances. Paratek is working to develop drugs that can interfere with this master switch, thereby disabling bacterial resistance mechanisms and rendering bacterial cells ultrasensitive to antimicrobial agents. Paratek has filed patents covering the use of the mar operon as a means of manipulating bacterial resistance to antibiotics and to non-antibiotic antibacterial compositions, disinfectants, and organic solvents.
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