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Infection and Immunity, November 2005, p. 7406-7412, Vol. 73, No. 11
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.11.7406-7412.2005

Analysis of a Heme-Dependent Signal Transduction System in Corynebacterium diphtheriae: Deletion of the chrAS Genes Results in Heme Sensitivity and Diminished Heme-Dependent Activation of the hmuO Promoter

Lori A. Bibb, Natalie D. King,{dagger} Carey A. Kunkle, and Michael P. Schmitt*

Laboratory of Bacterial Toxins, Division of Bacterial, Parasitic, and Allergenic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892

Received 21 June 2005/ Returned for modification 8 August 2005/ Accepted 11 August 2005

The Corynebacterium diphtheriae hmuO gene encodes a heme oxygenase that is involved in the utilization of heme as an iron source. Transcription of hmuO is activated by heme or hemoglobin and repressed by iron and DtxR. Previous studies with Escherichia coli showed that heme-dependent transcriptional activation of an hmuO promoter-lacZ fusion was dependent on the cloned C. diphtheriae chrA and chrS genes (chrAS), which encode the response regulator and sensor kinase, respectively, of a two-component signal transduction system. In this study, nonpolar deletions in the chrAS genes were constructed on the chromosome of C. diphtheriae. Mutations in chrAS resulted in marked reduction in heme-dependent transcription of hmuO, which indicates that the ChrA/S system is a key regulator at the hmuO promoter. However, low but significant levels of heme-specific transcriptional activity were observed at the hmuO promoter in the chrAS mutants, suggesting that an additional heme-dependent activator is involved in hmuO expression. The chrAS mutants were also sensitive to heme, which was observed only in stationary-phase cultures and correlated with reduced cell viability. The heme sensitivity of the mutants was not due to reduced expression of hmuO, and these results suggest that additional factors controlled by the ChrA/S system may be involved in protection against heme toxicity. Transcriptional analysis of the chrAS operon revealed that it was not autoregulated or affected by iron or heme levels.

* Corresponding author. Mailing address: DBPAP, CBER, FDA, Bldg.29, Room 108, 8800 Rockville Pike, Bethesda, MD 20892. Phone: (301) 435-2424. Fax: (301) 402-2776. E-mail: schmitt{at}cber.fda.gov.

Editor: J. T. Barbieri

{dagger} Present address: Witebsky Center for Microbial Pathogenesis and Immunology, Department of Microbiology and Immunology, The University of Buffalo, The State University of New York, Buffalo, NY 14214.

Infection and Immunity, November 2005, p. 7406-7412, Vol. 73, No. 11
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.11.7406-7412.2005




This article has been cited by other articles:

  • Smith, K. F., Bibb, L. A., Schmitt, M. P., Oram, D. M. (2009). Regulation and Activity of a Zinc Uptake Regulator, Zur, in Corynebacterium diphtheriae. J. Bacteriol. 191: 1595-1603 [Abstract] [Full Text]  
  • Kaur, A. P., Lansky, I. B., Wilks, A. (2009). The Role of the Cytoplasmic Heme-binding Protein (PhuS) of Pseudomonas aeruginosa in Intracellular Heme Trafficking and Iron Homeostasis. J. Biol. Chem. 284: 56-66 [Abstract] [Full Text]  
  • Kunkle, C. A., Schmitt, M. P. (2007). Comparative Analysis of hmuO Function and Expression in Corynebacterium Species. J. Bacteriol. 189: 3650-3654 [Abstract] [Full Text]  
  • Bibb, L. A., Kunkle, C. A., Schmitt, M. P. (2007). The ChrA-ChrS and HrrA-HrrS Signal Transduction Systems Are Required for Activation of the hmuO Promoter and Repression of the hemA Promoter in Corynebacterium diphtheriae. Infect. Immun. 75: 2421-2431 [Abstract] [Full Text]  
  • Wennerhold, J., Bott, M. (2006). The DtxR Regulon of Corynebacterium glutamicum.. J. Bacteriol. 188: 2907-2918 [Abstract] [Full Text]  


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