J. Bacteriol., 07 1996, 3803-3808, Vol 178, No. 13
Copyright © 1996, American Society for Microbiology

Oxygen-controlled regulation of the flavohemoglobin gene in Bacillus subtilis

M LaCelle, M Kumano, K Kurita, K Yamane, P Zuber and MM Nakano
Department of Biochemistry and Molecular Biology, Louisiana State University Medical Center, Shreveport, Louisiana 71130-3932, USA.

A gene, hmp, which encodes a ubiquitous protein homologous to hemoglobin was isolated among genes from Bacillus subtilis that are induced under anaerobic conditions. The hmp protein belongs to the family of two-domain flavohemoproteins, homologs of which have been isolated from various organisms such as Escherichia coli, Alcaligenes eutrophus, and Saccharomyces cerevisiae. These proteins consist of an amino-terminal hemoglobin domain and a carboxy-terminal redox active site domain with potential binding sites for NAD(P)H and flavin adenine dinucleotide. The expression of hmp is strongly induced upon oxygen limitation, and the induction is dependent on a two-component regulatory pair, ResD and ResE, an anaerobic regulator, FNR, and respiratory nitrate reductase, NarGHJI. The requirement of FNR and NarGHJI for hmp expression is completely bypassed by the addition of nitrite in the culture medium, indicating that fnr is required for transcriptional activation of narGHJI, which produces nitrite, leading to induction of hmp expression. In contrast, induction of hmp was still dependent on resDE in the presence of nitrite. A defect in hmp in B. subtilis has no significant effect on anaerobic growth.

This article has been cited by other articles:

• Rogstam, A., Larsson, J. T., Kjelgaard, P., von Wachenfeldt, C. (2007). Mechanisms of Adaptation to Nitrosative Stress in Bacillus subtilis. J. Bacteriol. 189: 3063-3071 [Abstract] [Full Text]  
• Geng, H., Zhu, Y., Mullen, K., Zuber, C. S., Nakano, M. M. (2007). Characterization of ResDE-Dependent fnr Transcription in Bacillus subtilis. J. Bacteriol. 189: 1745-1755 [Abstract] [Full Text]  
• Nakano, M. M. (2006). Essential Role of Flavohemoglobin in Long-Term Anaerobic Survival of Bacillus subtilis.. J. Bacteriol. 188: 6415-6418 [Abstract] [Full Text]  
• Hartig, E., Hartmann, A., Schatzle, M., Albertini, A. M., Jahn, D. (2006). The Bacillus subtilis nrdEF Genes, Encoding a Class Ib Ribonucleotide Reductase, Are Essential for Aerobic and Anaerobic Growth. Appl. Environ. Microbiol. 72: 5260-5265 [Abstract] [Full Text]  
• Nakano, M. M., Geng, H., Nakano, S., Kobayashi, K. (2006). The Nitric Oxide-Responsive Regulator NsrR Controls ResDE-Dependent Gene Expression.. J. Bacteriol. 188: 5878-5887 [Abstract] [Full Text]  
• Cassanova, N., O'Brien, K. M., Stahl, B. T., McClure, T., Poyton, R. O. (2005). Yeast Flavohemoglobin, a Nitric Oxide Oxidoreductase, Is Located in Both the Cytosol and the Mitochondrial Matrix: EFFECTS OF RESPIRATION, ANOXIA, AND THE MITOCHONDRIAL GENOME ON ITS INTRACELLULAR LEVEL AND DISTRIBUTION. J. Biol. Chem. 280: 7645-7653 [Abstract] [Full Text]  
• Ohwaki, Y., Kawagishi-Kobayashi, M., Wakasa, K., Fujihara, S., Yoneyama, T. (2005). Induction of Class-1 Non-symbiotic Hemoglobin Genes by Nitrate, Nitrite and Nitric Oxide in Cultured Rice Cells. Plant Cell Physiol 46: 324-331 [Abstract] [Full Text]  
• Hartig, E., Geng, H., Hartmann, A., Hubacek, A., Munch, R., Ye, R. W., Jahn, D., Nakano, M. M. (2004). Bacillus subtilis ResD Induces Expression of the Potential Regulatory Genes yclJK upon Oxygen Limitation. J. Bacteriol. 186: 6477-6484 [Abstract] [Full Text]  
• Elvers, K. T., Wu, G., Gilberthorpe, N. J., Poole, R. K., Park, S. F. (2004). Role of an Inducible Single-Domain Hemoglobin in Mediating Resistance to Nitric Oxide and Nitrosative Stress in Campylobacter jejuni and Campylobacter coli. J. Bacteriol. 186: 5332-5341 [Abstract] [Full Text]  
• Moore, C. M., Nakano, M. M., Wang, T., Ye, R. W., Helmann, J. D. (2004). Response of Bacillus subtilis to Nitric Oxide and the Nitrosating Agent Sodium Nitroprusside. J. Bacteriol. 186: 4655-4664 [Abstract] [Full Text]  
• Geng, H., Nakano, S., Nakano, M. M. (2004). Transcriptional Activation by Bacillus subtilis ResD: Tandem Binding to Target Elements and Phosphorylation-Dependent and -Independent Transcriptional Activation. J. Bacteriol. 186: 2028-2037 [Abstract] [Full Text]  
• Nakano, S., Nakano, M. M., Zhang, Y., Leelakriangsak, M., Zuber, P. (2003). A regulatory protein that interferes with activator-stimulated transcription in bacteria. Proc. Natl. Acad. Sci. USA 100: 4233-4238 [Abstract] [Full Text]  
• Park, K.-W., Kim, K.-J., Howard, A. J., Stark, B. C., Webster, D. A. (2002). Vitreoscilla Hemoglobin Binds to Subunit I of Cytochrome bo Ubiquinol Oxidases. J. Biol. Chem. 277: 33334-33337 [Abstract] [Full Text]  
• Nakano, M. M. (2002). Induction of ResDE-Dependent Gene Expression in Bacillus subtilis in Response to Nitric Oxide and Nitrosative Stress. J. Bacteriol. 184: 1783-1787 [Abstract] [Full Text]  
• Kaur, R., Pathania, R., Sharma, V., Mande, S. C., Dikshit, K. L. (2002). Chimeric Vitreoscilla Hemoglobin (VHb) Carrying a Flavoreductase Domain Relieves Nitrosative Stress in Escherichia coli: New Insight into the Functional Role of VHb. Appl. Environ. Microbiol. 68: 152-160 [Abstract] [Full Text]  
• Marino, M., Ramos, H. C., Hoffmann, T., Glaser, P., Jahn, D. (2001). Modulation of Anaerobic Energy Metabolism of Bacillus subtilis by arfM (ywiD). J. Bacteriol. 183: 6815-6821 [Abstract] [Full Text]  
• Weber, R. E., Vinogradov, S. N. (2001). Nonvertebrate Hemoglobins: Functions and Molecular Adaptations. Physiol. Rev. 81: 569-628 [Abstract] [Full Text]  
• Nakano, M. M., Zhu, Y. (2001). Involvement of ResE Phosphatase Activity in Down-Regulation of ResD-Controlled Genes in Bacillus subtilis during Aerobic Growth. J. Bacteriol. 183: 1938-1944 [Abstract] [Full Text]  
• Ye, R. W., Tao, W., Bedzyk, L., Young, T., Chen, M., Li, L. (2000). Global Gene Expression Profiles of Bacillus subtilis Grown under Anaerobic Conditions. J. Bacteriol. 182: 4458-4465 [Abstract] [Full Text]  
• Nakano, M. M., Zheng, G., Zuber, P. (2000). Dual Control of sbo-alb Operon Expression by the Spo0 and ResDE Systems of Signal Transduction under Anaerobic Conditions in Bacillus subtilis. J. Bacteriol. 182: 3274-3277 [Abstract] [Full Text]  
• Gardner, A. M., Martin, L. A., Gardner, P. R., Dou, Y., Olson, J. S. (2000). Steady-state and Transient Kinetics of Escherichia coli Nitric-oxide Dioxygenase (Flavohemoglobin). THE B10 TYROSINE HYDROXYL IS ESSENTIAL FOR DIOXYGEN BINDING AND CATALYSIS. J. Biol. Chem. 275: 12581-12589 [Abstract] [Full Text]  
• Frey, A. D., Bailey, J. E., Kallio, P. T. (2000). Expression of Alcaligenes eutrophus Flavohemoprotein and Engineered Vitreoscilla Hemoglobin-Reductase Fusion Protein for Improved Hypoxic Growth of Escherichia coli. Appl. Environ. Microbiol. 66: 98-104 [Abstract] [Full Text]  
• Marino, M., Hoffmann, T., Schmid, R., Möbitz, H., Jahn, D. (2000). Changes in protein synthesis during the adaptation of Bacillus subtilis to anaerobic growth conditions. Microbiology 146: 97-105 [Abstract] [Full Text]  
• Zheng, G., Yan, L. Z., Vederas, J. C., Zuber, P. (1999). Genes of the sbo-alb Locus of Bacillus subtilis Are Required for Production of the Antilisterial Bacteriocin Subtilosin. J. Bacteriol. 181: 7346-7355 [Abstract] [Full Text]  
• Nakano, M. M., Zhu, Y., Haga, K., Yoshikawa, H., Sonenshein, A. L., Zuber, P. (1999). A Mutation in the 3-Phosphoglycerate Kinase Gene Allows Anaerobic Growth of Bacillus subtilis in the Absence of ResE Kinase. J. Bacteriol. 181: 7087-7097 [Abstract] [Full Text]  
• Hu, Y., Butcher, P. D., Mangan, J. A., Rajandream, M.-A., Coates, A. R. M. (1999). Regulation of hmp Gene Transcription in Mycobacterium tuberculosis: Effects of Oxygen Limitation and Nitrosative and Oxidative Stress. J. Bacteriol. 181: 3486-3493 [Abstract] [Full Text]  
• Hay, N. A., Tipper, D. J., Gygi, D., Hughes, C. (1999). A Novel Membrane Protein Influencing Cell Shape and Multicellular Swarming of Proteus mirabilis. J. Bacteriol. 181: 2008-2016 [Abstract] [Full Text]  
• Sartori, G., Aldegheri, L., Mazzotta, G., Lanfranchi, G., Tournu, H., Brown, A. J. P., Carignani, G. (1999). Characterization of a New Hemoprotein in the Yeast Saccharomyces cerevisiae. J. Biol. Chem. 274: 5032-5037 [Abstract] [Full Text]  
• Membrillo-Hernandez, J., Coopamah, M. D., Anjum, M. F., Stevanin, T. M., Kelly, A., Hughes, M. N., Poole, R. K. (1999). The Flavohemoglobin of Escherichia coli Confers Resistance to a Nitrosating Agent, a "Nitric Oxide Releaser," and Paraquat and Is Essential for Transcriptional Responses to Oxidative Stress. J. Biol. Chem. 274: 748-754 [Abstract] [Full Text]  
• Crawford, M. J., Goldberg, D. E. (1998). Regulation of the Salmonella typhimurium Flavohemoglobin Gene. A NEW PATHWAY FOR BACTERIAL GENE EXPRESSION IN RESPONSE TO NITRIC OXIDE. J. Biol. Chem. 273: 34028-34032 [Abstract] [Full Text]  
• Nakano, M. M., Hoffmann, T., Zhu, Y., Jahn, D. (1998). Nitrogen and Oxygen Regulation of Bacillus subtilis nasDEF Encoding NADH-Dependent Nitrite Reductase by TnrA and ResDE. J. Bacteriol. 180: 5344-5350 [Abstract] [Full Text]  
• Gardner, P. R., Gardner, A. M., Martin, L. A., Salzman, A. L. (1998). Nitric oxide dioxygenase: An enzymic function for flavohemoglobin. Proc. Natl. Acad. Sci. USA 95: 10378-10383 [Abstract] [Full Text]  
• Joshi, M., Mande, S., Dikshit, K. L. (1998). Hemoglobin Biosynthesis in Vitreoscilla stercoraria DW: Cloning, Expression, and Characterization of a New Homolog of a Bacterial Globin Gene. Appl. Environ. Microbiol. 64: 2220-2228 [Abstract] [Full Text]  
• Crawford, M. J., Goldberg, D. E. (1998). Role for the Salmonella Flavohemoglobin in Protection from Nitric Oxide. J. Biol. Chem. 273: 12543-12547 [Abstract] [Full Text]  
• Buisson, N., Labbe-Bois, R. (1998). Flavohemoglobin Expression and Function in Saccharomyces cerevisiae. NO RELATIONSHIP WITH RESPIRATION AND COMPLEX RESPONSE TO OXIDATIVE STRESS. J. Biol. Chem. 273: 9527-9533 [Abstract] [Full Text]  
• Hoffmann, T., Frankenberg, N., Marino, M., Jahn, D. (1998). Ammonification in Bacillus subtilis Utilizing Dissimilatory Nitrite Reductase Is Dependent on resDE. J. Bacteriol. 180: 186-189 [Abstract] [Full Text]  
• Gardner, P. R., Gardner, A. M., Martin, L. A., Dou, Y., Li, T., Olson, J. S., Zhu, H., Riggs, A. F. (2000). Nitric-oxide Dioxygenase Activity and Function of Flavohemoglobins. SENSITIVITY TO NITRIC OXIDE AND CARBON MONOXIDE INHIBITION. J. Biol. Chem. 275: 31581-31587 [Abstract] [Full Text]  
• Liu, L., Zeng, M., Hausladen, A., Heitman, J., Stamler, J. S. (2000). Protection from nitrosative stress by yeast flavohemoglobin. Proc. Natl. Acad. Sci. USA 97: 4672-4676 [Abstract] [Full Text]