Document Detail


The ABC transporter HrtAB confers resistance to hemin toxicity and is regulated in a hemin-dependent manner by the ChrAS two-component system in Corynebacterium diphtheriae.
MedLine Citation:
PMID:  20639324     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Corynebacterium diphtheriae, the causative agent of the severe respiratory disease diphtheria, utilizes hemin and hemoglobin as iron sources for growth in iron-depleted environments. Because of the toxicity of high levels of hemin and iron, these compounds are often tightly regulated in bacterial systems. In this report, we identify and characterize the C. diphtheriae hrtAB genes, which encode a putative ABC type transporter involved in conferring resistance to the toxic effects of hemin. Deletion of the hrtAB genes in C. diphtheriae produced increased sensitivity to hemin, which was complemented by a plasmid harboring the cloned hrtAB locus. The HrtAB system was not involved in the uptake and use of hemin as an iron source. The hrtAB genes are located on the C. diphtheriae genome upstream from the chrSA operon, which encodes a previously characterized two-component signal transduction system that regulates gene expression in a heme-dependent manner. The hrtB promoter is activated by the ChrAS system in the presence of hemin or hemoglobin, and mutations in the chrSA genes abolish heme-activated expression from the hrtB promoter. It was also observed that transcription from the hrtB promoter is reduced in a dtxR deletion mutant, suggesting that DtxR is required for optimal expression of hrtAB. Previous studies proposed that the ChrS sensor kinase may be responsive to an environmental signal, such as hemin. We show that specific point mutations in the ChrS N-terminal transmembrane domain result in a reduced ability to activate the hrtB promoter in the presence of a heme source, suggesting that this putative sensor region is essential for the detection of a signal produced in response to hemin exposure. This study shows that the HrtAB system is required for protection from hemin toxicity and that expression of the hrtAB genes is regulated by the ChrAS two-component system. This study demonstrates a direct correlation between the detection of heme or a heme-associated signal by the N-terminal sensor domain of ChrS and the transcriptional activation of the hrtAB genes.
Authors:
Lori A Bibb; Michael P Schmitt
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Publication Detail:
Type:  Journal Article     Date:  2010-07-16
Journal Detail:
Title:  Journal of bacteriology     Volume:  192     ISSN:  1098-5530     ISO Abbreviation:  J. Bacteriol.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-27     Completed Date:  2010-09-13     Revised Date:  2011-07-25    
Medline Journal Info:
Nlm Unique ID:  2985120R     Medline TA:  J Bacteriol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4606-17     Citation Subset:  IM    
Affiliation:
Laboratory of Respiratory and Special Pathogens, Division of Bacterial, Parasitic, and Allergenic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA.
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MeSH Terms
Descriptor/Qualifier:
ATP-Binding Cassette Transporters / genetics,  metabolism*
Bacterial Proteins / chemistry,  genetics,  metabolism*
Computational Biology
Corynebacterium diphtheriae / drug effects*,  genetics,  metabolism*
Gene Expression Regulation, Bacterial / drug effects,  genetics
Hemin / toxicity*
Hemoglobins / metabolism
Iron / metabolism
Mutagenesis, Site-Directed
Promoter Regions, Genetic / genetics
Chemical
Reg. No./Substance:
0/ATP-Binding Cassette Transporters; 0/Bacterial Proteins; 0/Hemoglobins; 16009-13-5/Hemin; 7439-89-6/Iron
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