Mouse models of infection with Mtb

The antitubercular activity of SRT and RES was evaluated in an acute and chronic infection model of C57BL/6 mice (12). Female C57BL/6 mice (6 to 8 weeks old) were infected aerosolly with Mtb H37Rv or Erdman. Three to four animals were sacrificed on day 1 to determine the number of bacteria implanted in the lungs. Treatment was initiated 7 or 40 days after infection in the acute and chronic model, respectively. Drugs were administered by gavage once a day, 6 days a week. Mice were sacrificed at predetermined time points followed by harvesting of tissues and enumeration of Mtb CFU. A total of seven experiments (five acute and two chronic) were performed. All mice were housed in a biosafety level 3 (BSL3) laboratory and treated humanely. The Mac-SIRT1 KO mice (30) were a gift from X. Li (U.S. National Institute of Environmental Health Sciences). A total of three experiments were performed with Mac-SIRT1 KO and their littermate controls.