Virulence and Resistance to Superoxide, Low pH and Hydrogen Peroxide among Strains of Mycobacterium tuberculosis

Abstract

Six strains of Mycobacterium tuberculosis of different virulence in guinea-pigs were compared with regard to their resistance to low pH, to hydrogen peroxide (H202) at different pH values and to superoxide (-O,-). Low virulence was associated with susceptibility to H202 in native and isoniazid-resistant strains but not in laboratory-attenuated strain ~3 7~a . H,Oz resistance was only partly related to catalase content. Low virulence was not associated with susceptibility to an acid environment but the tuberculocidal effect of H202 was significantly increased at low pH. The strains were uniformly resistant to -02-and contained similar amounts of superoxide dismutase. The implications of these observations are discussed in the context of mechanisms of host defence in tuberculosis.

Susceptibility of Mycobacterium Leprae to the Bactericidal Activity of Mouse Peritoneal Macrophages and to Hydrogen Peroxide

“…We have also shown that catalase-negative strains of M . tuberculosis are killed in similar circumstances whereas catalasepositive strains are capable of survival, thus confirming the more extensive work of Jackett et al (1978). The implication is that M .…”

“…The concentration was chosen on the basis of a previous study on the susceptibility of M . tuberculosis to H202 (Jackett, Aber and Lowrie, 1978). Suspensions were incubated at 37"C, and at appropriate intervals samples of these suspensions were removed and viable counts were made.…”

How macrophages kill tubercle bacilli

“…superoxide-generating system was tested (Jackett et al, 1978a). Only the peroxidesusceptible strains of tubercle bacilli were killed by products of this system ( fig.…”

The Oxidation-sensing Regulator (MosR) Is a New Redox-dependent Transcription Factor in Mycobacterium tuberculosis

“…To survive inside macrophages, M. tuberculosis must withstand reactive oxygen species (ROS) 2 produced by phagocyte oxidase (NOX2/gp91 phox ) and reactive nitrogen species (RNS) produced by inducible nitric-oxide synthase in the macrophage (2). The bacterium is aided by several antioxidant defenses including a thick cell wall rich in lipoarabinomannan, cyclopropanated mycolic acid, and phenolic glycolipid I (PGL-1) (3), millimolar concentration of mycothiol (4,5), protective enzymes such as catalase (KatG) (6), superoxide dismutases (SodA and SodC) (7,8), peroxidase and peroxynitrite reductase complex (AhpC, AhpD, SucB, and Lpd) (9,10), and DNA-binding proteins such as Lrs2 (11), as well as an arsenal of exported proteins (12). However, little is known of transcriptional regulators sensitive to oxidation in M. tuberculosis that control these cellular defenses.…”