Cidality of Mtb targets by AS-silencing in lung infection in mice.

<p>(A). Overall survival kinetics of Mtb AS-recombinants and the WT and vector controls in the lungs of mice (n = 3) on the days-3, 7, 14, 28, 42, 56. The control strains showed expected course of infection in the lungs; there was no difference in both these strains (WT and vector, ns, P = 0.3105, two-way ANOVA). The treatment control (Rifampicin treatment of WT Mtb) showed expected cidality pattern of ~3.8 log₁₀ cfu reduction, represented by the turquoise and brown chequered bars on day-3 and day-28. Target <i>ilvB</i> (however, significantly different from control, *P = 0.0402, two-way ANOVA) was non-cidal in-vivo. The graph is a plot of log₁₀ cfu/lung of mice <i>vs</i>. number of days. The cidality emerged in the rank order of <i>rpoB>aroK>ppk>rpoC</i>. Data was statistically significant (**P = 0.0086 to *P = 0.0402, two-way ANOVA) from 14 day onwards. (B). Lung pictures on the day 28 (4^thweek), visually demonstrate in-vivo cidality by a clearing of infection in the lungs with the healing of granuloma due to the killing of the respective AS-recombinant of Mtb in the order of <i>rpoB>aroK>rpoC>ppk</i>; correlating with the cfu data outcome (panel <b>C</b>). The maximum healing was visible in the rifampicin treated lungs, correlating with the cidality shown in the cfu histogram. The control strains (WT and V) demonstrated the fully formed visible granulomas in the lungs. (C). Final histograms of AS-based cidality on Day-56 (8^th week) graphs. A statistically significant robust data with error bars (SEM) from triplicates (n = 3), shows the cidality pattern in the order of <i>rpoB</i>(3.9)> <i>aroK</i>(2.4)<i>> ppk</i>(1.6)<i>> rpoC</i>(1.59)><i>ilvB</i>(0.36).