The authors built unmarked single- and double-knockout Mycobacterium tuberculosis strains lacking MTS0997, MTS1338, or both, profiled whole-genome expression during culture growth, in IFN-γ-activated and non-activated murine bone marrow-derived macrophages, and in infection of highly TB-susceptible I/St mice, and found that MTS0997 deletion had the larger impact on bacterial biology (altered succinate/fumarate respiration, up-regulated ESX-1 secretion genes, increased virulence in mice, reduced lung pro-inflammatory cytokine production), that all three knockout strains killed mice significantly faster than wild type while lung CFU counts at 6 weeks did not differ, and that B-cell and MHC-II-expressing lung cell populations differed between single- and double-knockout infections, suggesting
The authors built unmarked single- and double-knockout Mycobacterium tuberculosis strains lacking MTS0997, MTS1338, or both, profiled whole-genome expression during culture growth, in IFN-γ-activated and non-activated murine bone marrow-derived macrophages, and in infection of highly TB-susceptible I/St mice, and found that MTS0997 deletion had the larger impact on bacterial biology (altered succinate/fumarate respiration, up-regulated ESX-1 secretion genes, increased virulence in mice, reduced lung pro-inflammatory cytokine production), that all three knockout strains killed mice significantly faster than wild type while lung CFU counts at 6 weeks did not differ, and that B-cell and MHC-II-expressing lung cell populations differed between single- and double-knockout infections, suggesting