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MAR Development Program Paratek is exploiting the discovery of the Mar operon, a novel "master switch" that controls expression of over 80 genes in clinically important bacteria. When activated, the Mar system initiates a number of bacterial survival and defense mechanisms, including processes whereby bacteria establish infections and develop resistance to antibiotics. Paratek has used structure based drug design (SBDD) coupled with whole cell assays, in vitro experiments, and animal models of infection to synthesize and characterize series of small organic molecules (MAR inhibitors) that target and inhibit MarA and related proteins. Paratek has shown that these MAR inhibitors prevent infection in clinically relevant models of infection. MAR inhibitors can be envisioned as broad-spectrum agents that decrease bacterial virulence and thereby prevent infection in many clinically relevant settings where patients are at high-risk of contracting bacterial infections. Since they do not kill or inhibit bacterial growth, MAR inhibitors represent a new paradigm of antibacterial treatment. It is believed that MAR inhibitors will not contribute to the problem of bacterial resistance development and, in fact, may help overcome it. Paratek is developing its lead MAR inhibitors for the treatment of nosocomial respiratory and urinary tract infections as well as for use against potential biological warfare agents. MAR inhibitors might also be useful as adjunct therapy to improve the effectiveness of currently available antibiotics.
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