Thiol peroxidase is an important component of streptococcus pneumoniae in oxygenated environments

Barak Hajaj, Hasan Yesilkaya, Rachel Benisty, Maayan David, Peter W. Andrew, Nurith Porat

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Streptococcus pneumoniae is an aerotolerant Gram-positive bacterium that causes an array of diseases, including pneumonia, otitis media, and meningitis. During aerobic growth, S. pneumoniae produces high levels of H2O2. Since S. pneumoniae lacks catalase, the question of how it controls H2O2 levels is of critical importance. The psa locus encodes an ABC Mn2+ -permease complex (psaBCA) and a putative thiol peroxidase, tpxD. This study shows that tpxD encodes a functional thiol peroxidase involved in the adjustment of H2O2 homeostasis in the cell. Kinetic experiments showed that recombinant TpxD removed H2O2 efficiently. However, in vivo experiments revealed that TpxD detoxifies only a fraction of the H2O2 generated by the pneumococcus. Mass spectrometry analysis demonstrated that TpxD Cys58 undergoes selective oxidation in vivo, under conditions where H2O2 is formed, confirming the thiol peroxidase activity. Levels of TpxD expression and synthesis in vitro were significantly increased in cells grown under aerobic versus anaerobic conditions. The challenge with D39 and TIGR4 with H2O2 resulted in tpxD upregulation, while psaBCA expression was oppositely affected. However, the challenge of ΔtpxD mutants with H2O2 did not affect psaBCA, implying that TpxD is involved in the regulation of the psa operon, in addition to its scavenging activity. Virulence studies demonstrated a notable difference in the survival time of mice infected intranasally with D39 compared to that of mice infected intranasally with D39ΔtpxD. However, when bacteria were administered directly into the blood, this difference disappeared. The findings of this study suggest that TpxD constitutes a component of the organism's fundamental strategy to fine-tune cellular processes in response to H2O2.

Original languageEnglish
Pages (from-to)4333-4343
Number of pages11
JournalInfection and Immunity
Volume80
Issue number12
DOIs
StatePublished - 14 Dec 2012
Externally publishedYes

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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