Thiol peroxidase involved in S. pneumoniae defenses
medwireNews: The Streptococcus pneumoniae bacteria defends itself from high levels of hydrogen peroxide (H202) with the help of thiol peroxidase (TpxD), research shows.
S.pneumoniae lacks the catalase proteins to protect against oxidative stress, but the S.pneumoniae gene tpxD encodes a functional TpxD protein involved in the scavenging of H202, report investigators.
Led by Nurith Porat (Soroka University Medical Center, Beer Sheva, Israel), the researchers note that the pneumococcus is exposed to different levels of oxygen during infection.
During the aerobic growth phase, S.pneumoniae produces high levels of H202, which can induce cell death at high concentrations.
Writing in Infection and Immunology, Porat et al explain that some key enzymes involved in the oxidative response have been detailed, such as superoxide dismutase, NADH oxidase, and alkyl hydroperoxidase, but the complete response is unknown.
In the first experiment, the group showed that the protein TpxD possessed peroxidase activity, with recombinant TpxD catalyzing the reduction of H202.
In vivo experiments, however, showed that TpxD detoxified only a fraction of H202 generated by the pneumococcus.
In a mass spectrometry analysis, TpxD-cysteine underwent selective oxidation in vivo under the similar conditions where H202 is formed, "confirming the thiol peroxidase activity," write Porat and colleagues.
The expression and synthesis in vitro of TpxD were significantly increased in cells grown under aerobic compared with cells grown under anaerobic conditions.
The researchers explain that the psa locus of S. pneumoniae encodes an ABC Mn2+-permease complex (psaBCA) upstream of coding for the thiol peroxidase.
Looking at the relationship between expression levels of psaBCA and tpxD, it was found that psaBCA was downregulated under aerobic versus anaerobic conditions and in response to H202.
The co-regulation of psaBCA and tpxD was established in vivo by comparing the expression levels of infected mice, with the experiment showing an inverse correlation in the expression levels.
"Our data demonstrate that the effect of H202 on psaBCA expression is mediated by TpxD," report Porat et al. "This may constitute one of the components of the organism's fundamental strategy to fine-tune cellular processes in response to H202."
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