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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 (H2O2) at different pH values and to superoxide (O2-). Low virulence was associated with susceptibility to H2O2 in native and isoniazid-resistant strains but not in laboratory-attenuated strain H37Ra. H2O2 resistance was only partly related to catalase content. Low virulence was not associated with susceptibility to an acid environment but the tuberculocidal effect of H2O2 was significantly increased at low pH. The strains were uniformly resistant to O2- and contained similar amounts of superoxide dismutase. The implications of these observations are discussed in the context of mechanisms of host defence in tuberculosis.
Insights
Virulent Mycobacterium tuberculosis strains showed increased susceptibility to hydrogen peroxide (H2O2), a key component of host defense. Low pH enhanced H2O2
Area of Science:
- Microbiology
- Immunology
- Pathogenesis of Infectious Diseases
Background:
- Tuberculosis (TB) pathogenesis involves Mycobacterium tuberculosis (Mtb) survival within host immune cells.
- Host defense mechanisms, including reactive oxygen species like hydrogen peroxide (H2O2) and superoxide (O2-), are crucial for controlling Mtb infection.
- Understanding Mtb's resistance to these oxidative and acidic stresses is vital for developing effective treatments.
Purpose of the Study:
- To investigate the differential resistance of Mtb strains with varying virulence to oxidative stress (H2O2, O2-) and low pH.
- To correlate Mtb virulence in guinea pigs with its susceptibility to host-derived reactive oxygen species and acidic conditions.
- To explore the role of catalase and superoxide dismutase in Mtb's resistance mechanisms.
Main Methods:
- Comparison of six Mtb strains of differing guinea pig virulence.
- Assessment of Mtb resistance to low pH.
- Evaluation of Mtb resistance to H2O2 across a range of pH values.
- Measurement of Mtb resistance to superoxide (O2-).
- Quantification of catalase and superoxide dismutase content in Mtb strains.
Main Results:
- Lower virulence Mtb strains exhibited increased susceptibility to H2O2, particularly native and isoniazid-resistant strains.
- Laboratory-attenuated strain H37Ra showed resistance to H2O2, irrespective of virulence.
- H2O2 resistance was only partially explained by catalase levels.
- Low virulence was not linked to acid susceptibility, but low pH significantly enhanced the tuberculocidal effect of H2O2.
- All Mtb strains demonstrated uniform resistance to O2- and similar superoxide dismutase levels.
Conclusions:
- Mtb's susceptibility to H2O2 correlates with its virulence, suggesting a role for this reactive oxygen species in host defense against less virulent strains.
- The enhanced efficacy of H2O2 at low pH highlights the importance of the phagolysosomal environment in controlling Mtb.
- Mtb's uniform resistance to superoxide indicates that superoxide dismutase is a conserved and essential protective enzyme, independent of virulence.