Figure 2. INH treatment of Mm-infected larvae results in a biphasic EBA with persistence of tolerant organisms.
(A) Authors’ rendition of human clinical EBA data (see Figure 1 of (Jindani et al., 2003)) showing the rate of clearance of Mtb from sputum in patients with previously untreated, smear-positive pulmonary tuberculosis, upon treatment with INH and/or RIF.
(B and C) Twenty larvae were infected with 300 Mm and treated with 290 µM INH beginning 3 dpi. Each larva was imaged daily for 8 dpt, and bacterial burdens quantified by FPC. (B) Representative larva imaged at the beginning of treatment (0 dpt), and again at five and seven dpt. Arrow, granuloma, arrowhead, macrophage containing persistent bacteria. (C) EBA curve for INH-treated larvae, showing the mean log10 FPC change from day 0. Error bars represent SEM. EBA was calculated as described in the Experimental Procedures.
(D–F) Ten larvae per group were infected with 300 Mm and were serially imaged for enumeration of bacterial burden by FPC. (D) Larvae were treated with 388 µM RIF or left untreated, beginning 1 dpi. Mean FPC and SEM are shown. (E) Larvae were treated with 290 µM INH, 388 µM RIF, or a combination of both drugs beginning at 3 dpi. Data analyzed as in (C). (F) Representative INH-RIF treated larvae annotated as in (B).