You are here: Home Published Research Overlapping and complementary oxidative stress defense mechanisms in nontypeable Haemophilus influenzae.

Alistair Harrison, Beth D Baker, and Robert S Munson (2014)

Overlapping and complementary oxidative stress defense mechanisms in nontypeable Haemophilus influenzae.

Journal of bacteriology.

The Gram-negative commensal bacterium nontypeable Haemophilus influenzae (NTHi) can cause respiratory tract diseases that include otitis media, sinusitis, exacerbations of chronic obstructive pulmonary disease and bronchitis. During colonization and infection, NTHi withstands oxidative stress generated by reactive oxygen species produced endogenously, by the host and by other co-pathogens and flora. These reactive oxygen species include superoxide, hydrogen peroxide (H2O2)and hydroxyl radicals. This killing is amplified by iron, via the Fenton reaction. We previously identified genes that encode proteins with putative roles in protection of the NTHi isolate, strain 86-028NP against oxidative stress. These include catalase (HktE), peroxiredoxin/glutaredoxin (PgdX) and a ferritin-like protein (Dps). Strains were generated with mutations in hktE, pgdX and dps. The hktE mutant and a pgdX-hktE double mutant were more sensitive to killing by H2O2, when compared to the parent. Conversely, the pgdX mutant was more resistant to H2O2 due to increased catalase activity. Supporting the role of killing via the Fenton reaction, binding of iron by Dps significantly mitigated the effect of H2O2-mediated killing. NTHi thus utilizes several effectors to resist oxidative stress and regulation of free iron is critical to this protection. These mechanisms will be important for successful colonization and infection by this opportunistic human pathogen.

 
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