This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pericone, C. D. Articles by Weiser, J. N. Search for Related Content PubMed PubMed Citation Articles by Pericone, C. D. Articles by Weiser, J. N.

Factors Contributing to Hydrogen Peroxide Resistance in Streptococcus pneumoniae Include Pyruvate Oxidase (SpxB) and Avoidance of the Toxic Effects of the Fenton Reaction

Christopher D. Pericone,^1, Sunny Park,² James A. Imlay,² and Jeffrey N. Weiser^1,3*

Departments of Microbiology,¹ Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104,³ Department of Microbiology, University of Illinois, Urbana, Illinois 61801²

Received 30 May 2003/ Accepted 11 September 2003

Aerobic growth of Streptococcus pneumoniae results in production of amounts of hydrogen peroxide (H₂O₂) that may exceed 1 mM in the surrounding media. H₂O₂ production by S. pneumoniae has been shown to kill or inhibit the growth of other respiratory tract flora, as well as to have cytotoxic effects on host cells and tissue. The mechanisms allowing S. pneumoniae, a catalase-deficient species, to survive endogenously generated concentrations of H₂O₂ that are sufficient to kill other bacterial species is unknown. In the present study, pyruvate oxidase (SpxB), the enzyme responsible for endogenous H₂O₂ production, was required for survival during exposure to high levels (20 mM) of exogenously added H₂O₂. Pretreatment with H₂O₂ did not increase H₂O₂ resistance in the mutant, suggesting that SpxB activity itself is required, rather than an H₂O₂-inducible pathway. SpxB mutants synthesized 85% less acetyl-phosphate, a potential source of ATP. During H₂O₂ exposure, ATP levels decreased more rapidly in spxB mutants than in wild-type cells, suggesting that the increased killing of spxB mutants was due to more rapid ATP depletion. Together, these data support the hypothesis that S. pneumoniae SpxB contributes to an H₂O₂-resistant energy source that maintains viability during oxidative stress. Thus, SpxB is required for resistance to the toxic by-product of its own activity. Although H₂O₂-dependent hydroxyl radical production and the intracellular concentration of free iron were similar to that of Escherichia coli, killing by H₂O₂ was unaffected by iron chelators, suggesting that S. pneumoniae has a novel mechanism to avoid the toxic effects of the Fenton reaction.

Present address: Department of Microbiology, College of Physicians and Surgeons, Columbia University, New York, NY 10032

This article has been cited by other articles:

• Kreth, J., Zhang, Y., Herzberg, M. C. (2008). Streptococcal Antagonism in Oral Biofilms: Streptococcus sanguinis and Streptococcus gordonii Interference with Streptococcus mutans. J. Bacteriol. 190: 4632-4640 [Abstract] [Full Text]  
• Taniai, H., Iida, K.-i., Seki, M., Saito, M., Shiota, S., Nakayama, H., Yoshida, S.-i. (2008). Concerted Action of Lactate Oxidase and Pyruvate Oxidase in Aerobic Growth of Streptococcus pneumoniae: Role of Lactate as an Energy Source. J. Bacteriol. 190: 3572-3579 [Abstract] [Full Text]  
• Jakubovics, N. S., Gill, S. R., Iobst, S. E., Vickerman, M. M., Kolenbrander, P. E. (2008). Regulation of Gene Expression in a Mixed-Genus Community: Stabilized Arginine Biosynthesis in Streptococcus gordonii by Coaggregation with Actinomyces naeslundii. J. Bacteriol. 190: 3646-3657 [Abstract] [Full Text]  
• Park, B., Nizet, V., Liu, G. Y. (2008). Role of Staphylococcus aureus Catalase in Niche Competition against Streptococcus pneumoniae. J. Bacteriol. 190: 2275-2278 [Abstract] [Full Text]  
• Battig, P., Muhlemann, K. (2008). Influence of the spxB Gene on Competence in Streptococcus pneumoniae. J. Bacteriol. 190: 1184-1189 [Abstract] [Full Text]  
• Regev-Yochay, G., Trzcinski, K., Thompson, C. M., Lipsitch, M., Malley, R. (2007). SpxB Is a Suicide Gene of Streptococcus pneumoniae and Confers a Selective Advantage in an In Vivo Competitive Colonization Model. J. Bacteriol. 189: 6532-6539 [Abstract] [Full Text]  
• Macomber, L., Rensing, C., Imlay, J. A. (2007). Intracellular Copper Does Not Catalyze the Formation of Oxidative DNA Damage in Escherichia coli. J. Bacteriol. 189: 1616-1626 [Abstract] [Full Text]  
• Jang, S., Imlay, J. A. (2007). Micromolar Intracellular Hydrogen Peroxide Disrupts Metabolism by Damaging Iron-Sulfur Enzymes. J. Biol. Chem. 282: 929-937 [Abstract] [Full Text]  
• Lanie, J. A., Ng, W.-L., Kazmierczak, K. M., Andrzejewski, T. M., Davidsen, T. M., Wayne, K. J., Tettelin, H., Glass, J. I., Winkler, M. E. (2007). Genome Sequence of Avery's Virulent Serotype 2 Strain D39 of Streptococcus pneumoniae and Comparison with That of Unencapsulated Laboratory Strain R6. J. Bacteriol. 189: 38-51 [Abstract] [Full Text]  
• Goffin, P., Muscariello, L., Lorquet, F., Stukkens, A., Prozzi, D., Sacco, M., Kleerebezem, M., Hols, P. (2006). Involvement of Pyruvate Oxidase Activity and Acetate Production in the Survival of Lactobacillus plantarum during the Stationary Phase of Aerobic Growth. Appl. Environ. Microbiol. 72: 7933-7940 [Abstract] [Full Text]  
• Schreiner, M. E., Riedel, C., Holatko, J., Patek, M., Eikmanns, B. J. (2006). Pyruvate:Quinone Oxidoreductase in Corynebacterium glutamicum: Molecular Analysis of the pqo Gene, Significance of the Enzyme, and Phylogenetic Aspects. J. Bacteriol. 188: 1341-1350 [Abstract] [Full Text]  
• Iyer, R., Baliga, N. S., Camilli, A. (2005). Catabolite Control Protein A (CcpA) Contributes to Virulence and Regulation of Sugar Metabolism in Streptococcus pneumoniae. J. Bacteriol. 187: 8340-8349 [Abstract] [Full Text]  
• Ng, W.-L., Tsui, H.-C. T., Winkler, M. E. (2005). Regulation of the pspA Virulence Factor and Essential pcsB Murein Biosynthetic Genes by the Phosphorylated VicR (YycF) Response Regulator in Streptococcus pneumoniae. J. Bacteriol. 187: 7444-7459 [Abstract] [Full Text]  
• Park, S., You, X., Imlay, J. A. (2005). Substantial DNA damage from submicromolar intracellular hydrogen peroxide detected in Hpx- mutants of Escherichia coli. Proc. Natl. Acad. Sci. USA 102: 9317-9322 [Abstract] [Full Text]  
• Wolfe, A. J. (2005). The Acetate Switch. Microbiol. Mol. Biol. Rev. 69: 12-50 [Abstract] [Full Text]  
• Belanger, A. E., Clague, M. J., Glass, J. I., LeBlanc, D. J. (2004). Pyruvate Oxidase Is a Determinant of Avery's Rough Morphology. J. Bacteriol. 186: 8164-8171 [Abstract] [Full Text]  
• Ulijasz, A. T., Andes, D. R., Glasner, J. D., Weisblum, B. (2004). Regulation of Iron Transport in Streptococcus pneumoniae by RitR, an Orphan Response Regulator. J. Bacteriol. 186: 8123-8136 [Abstract] [Full Text]  
• Johnston, J. W., Myers, L. E., Ochs, M. M., Benjamin, W. H. Jr., Briles, D. E., Hollingshead, S. K. (2004). Lipoprotein PsaA in Virulence of Streptococcus pneumoniae: Surface Accessibility and Role in Protection from Superoxide. Infect. Immun. 72: 5858-5867 [Abstract] [Full Text]  
• Yamamoto, Y., Fukui, K., Koujin, N., Ohya, H., Kimura, K., Kamio, Y. (2004). Regulation of the Intracellular Free Iron Pool by Dpr Provides Oxygen Tolerance to Streptococcus mutans. J. Bacteriol. 186: 5997-6002 [Abstract] [Full Text]  
• Lorquet, F., Goffin, P., Muscariello, L., Baudry, J.-B., Ladero, V., Sacco, M., Kleerebezem, M., Hols, P. (2004). Characterization and Functional Analysis of the poxB Gene, Which Encodes Pyruvate Oxidase in Lactobacillus plantarum. J. Bacteriol. 186: 3749-3759 [Abstract] [Full Text]