Therapeutics: E. coli DNA adenine methyltransferase (Dam)
Cell studies suggest inhibiting E. coli Dam could help enhance the sensitivity of the bacterial infection to antibiotics. In a cultured strain of E. coli, knockout of Dam plus an antibiotic - Azactam aztreonam, Meropen meropenem, generic ampicillin or generic cephalexin - decreased bacterial survival compared with normal Dam expression and antibiotic. In another cultured E. coli strain, Dam knockout plus an antibiotic - Noroxin norfloxacin, generic ofloxacin or generic ciprofloxacin - decreased survival. In a ciprofloxacin-resistant strain of E. coli, Dam knockout increased sensitivity to ciprofloxacin compared with normal Dam expression. Next steps include identifying and testing small molecule Dam inhibitors to treat bacterial infection.
Bristol-Myers Squibb Co. markets Azactam to treat Gram-negative bacterial infection. ...