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Journal of Bacteriology, February 1999, p. 1229-1237, Vol. 181, No. 4
0021-9193/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Impact of either Elevated or Decreased Levels of Cytochrome bd Expression on Shigella flexneri Virulence

Sing Sing Way,1 Sandra Sallustio,1,dagger Richard S. Magliozzo,2 and Marcia B. Goldberg1,*

Department of Microbiology and Immunology1 and Department of Physiology and Biophysics,2 Albert Einstein College of Medicine, Bronx, New York 10461-1602

Received 9 June 1998/Accepted 10 December 1998

Shigella spp. are the major cause of bacillary dysentery worldwide. The pathogenic process involves bacterial invasion and lysis of the phagocytic vacuole, followed by replication and movement within the cell cytoplasm and, ultimately, spread directly into adjacent cells. This study demonstrates that S. flexneri cytochrome bd expression is necessary for normal intracellular survival and virulence. Cytochrome bd is one of two terminal oxidases in the bacterial respiratory chain that reduce molecular oxygen to water, utilizing intermediates shuttled through the electron transport chain. S. flexneri mutants that contain a disruption in the cydC locus, which leads to defective cytochrome bd expression, or in the riboflavin (ribE) or ubiquinol-8 (ubiH) biosynthetic pathway, which leads to elevated cytochrome bd expression, were evaluated in intracellular survival and virulence assays. The cydC mutant formed significantly smaller plaques, had significantly decreased intracellular survival, and had a 100-fold increase in lethal dose for mice compared with the wild type. The ribE and ubiH mutants each formed significantly larger plaques and had a 10-fold decrease in lethal dose for mice compared with the wild type. The data indicate that expression of cytochrome bd is required for S. flexneri intracellular survival and virulence.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461-1602. Phone: (718) 430-2118. Fax: (718) 430-8711. E-mail: mgoldber{at}aecom.yu.edu.

dagger Present address: Department of Emergency Medicine, Mount Sinai Hospital Center, New York, NY 10029.

Journal of Bacteriology, February 1999, p. 1229-1237, Vol. 181, No. 4
0021-9193/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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