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 Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Elgrably-Weiss, M. Articles by Altuvia, S. Search for Related Content PubMed PubMed Citation Articles by Elgrably-Weiss, M. Articles by Altuvia, S.

A Salmonella enterica Serovar Typhimurium hemA Mutant Is Highly Susceptible to Oxidative DNA Damage

Department of Molecular Genetics and Biotechnology, The Hebrew University-Hadassah Medical School, 91120 Jerusalem, Israel,¹ Department of Microbiology, University of Illinois, Urbana, Illinois 61801²

Received 11 April 2002/ Accepted 16 April 2002

The first committed step in the biosynthesis of heme, an important cofactor of two catalases and a number of cytochromes, is catalyzed by the hemA gene product. Salmonella enterica serovar Typhimurium hemA26::Tn10d (hemA26) was identified in a genetic screen of insertion mutants that were sensitive to hydrogen peroxide. Here we show that the hemA26 mutant respires at half the rate of wild-type cells and is highly susceptible to the effects of oxygen species. Exposure of the hemA26 strain to hydrogen peroxide results in extensive DNA damage and cell death. The chelation of intracellular free iron fully abrogates the sensitivity of this mutant, indicating that the DNA damage results from the iron-catalyzed formation of hydroxyl radicals. The inactivation of heme synthesis does not change the amount of intracellular iron, but by diminishing the rate of respiration, it apparently increases the amount of reducing equivalents available to drive the Fenton reaction. We also report that hydrogen peroxide has opposite effects on the expression of hemA and hemH, the first and last genes of heme biosynthesis pathway, respectively. hemA mRNA levels decrease, while the transcription of hemH is induced by hydrogen peroxide, in an oxyR-dependent manner. The oxyR-dependent induction is suppressed under conditions that accelerate the Fenton reaction by a mechanism that is not yet understood.

This article has been cited by other articles:

• Shifrin, Y., Peleg, A., Ilan, O., Nadler, C., Kobi, S., Baruch, K., Yerushalmi, G., Berdichevsky, T., Altuvia, S., Elgrably-Weiss, M., Abe, C., Knutton, S., Sasakawa, C., Ritchie, J. M., Waldor, M. K., Rosenshine, I. (2008). Transient Shielding of Intimin and the Type III Secretion System of Enterohemorrhagic and Enteropathogenic Escherichia coli by a Group 4 Capsule. J. Bacteriol. 190: 5063-5074 [Abstract] [Full Text]  
• Kitphati, W., Ngok-ngam, P., Suwanmaneerat, S., Sukchawalit, R., Mongkolsuk, S. (2007). Agrobacterium tumefaciens fur Has Important Physiological Roles in Iron and Manganese Homeostasis, the Oxidative Stress Response, and Full Virulence. Appl. Environ. Microbiol. 73: 4760-4768 [Abstract] [Full Text]  
• Chang, W., Small, D. A., Toghrol, F., Bentley, W. E. (2006). Global Transcriptome Analysis of Staphylococcus aureus Response to Hydrogen Peroxide. J. Bacteriol. 188: 1648-1659 [Abstract] [Full Text]  
• Nadler, C., Shifrin, Y., Nov, S., Kobi, S., Rosenshine, I. (2006). Characterization of Enteropathogenic Escherichia coli Mutants That Fail To Disrupt Host Cell Spreading and Attachment to Substratum. Infect. Immun. 74: 839-849 [Abstract] [Full Text]  
• Peleg, A., Shifrin, Y., Ilan, O., Nadler-Yona, C., Nov, S., Koby, S., Baruch, K., Altuvia, S., Elgrably-Weiss, M., Abe, C. M., Knutton, S., Saper, M. A., Rosenshine, I. (2005). Identification of an Escherichia coli Operon Required for Formation of the O-Antigen Capsule. J. Bacteriol. 187: 5259-5266 [Abstract] [Full Text]  
• Panek, H. R., O'Brian, M. R. (2004). KatG Is the Primary Detoxifier of Hydrogen Peroxide Produced by Aerobic Metabolism in Bradyrhizobium japonicum. J. Bacteriol. 186: 7874-7880 [Abstract] [Full Text]  
• Macvanin, M., Ballagi, A., Hughes, D. (2004). Fusidic Acid-Resistant Mutants of Salmonella enterica Serovar Typhimurium Have Low Levels of Heme and a Reduced Rate of Respiration and Are Sensitive to Oxidative Stress. Antimicrob. Agents Chemother. 48: 3877-3883 [Abstract] [Full Text]