Two small c‐type cytochromes affect virulence gene expression in Bacillus anthracis
Open Access
- 19 March 2009
- journal article
- Published by Wiley in Molecular Microbiology
- Vol. 72 (1), 109-123
- https://doi.org/10.1111/j.1365-2958.2009.06627.x
Abstract
Regulated expression of the genes for anthrax toxin proteins is essential for the virulence of the pathogenic bacterium Bacillus anthracis. Induction of toxin gene expression depends on several factors, including temperature, bicarbonate levels, and metabolic state of the cell. To identify factors that regulate toxin expression, transposon mutagenesis was performed under non-inducing conditions and mutants were isolated that untimely expressed high levels of toxin. A number of these mutations clustered in the haem biosynthetic and cytochrome c maturation pathways. Genetic analysis revealed that two haem-dependent, small c-type cytochromes, CccA and CccB, located on the extracellular surface of the cytoplasmic membrane, regulate toxin gene expression by affecting the expression of the master virulence regulator AtxA. Deregulated AtxA expression in early exponential phase resulted in increased expression of toxin genes in response to loss of the CccA-CccB signalling pathway. This is the first function identified for these two small c-type cytochromes of Bacillus species. Extension of the transposon screen identified a previously uncharacterized protein, BAS3568, highly conserved across many bacterial and archeal species, as involved in cytochrome c activity and virulence regulation. These findings are significant not only to virulence regulation in B. anthracis, but also to analysis of virulence regulation in many pathogenic bacteria and to the study of cytochrome c activity in Gram-positive bacteria.Keywords
This publication has 57 references indexed in Scilit:
- The Bicarbonate Transporter Is Essential for Bacillus anthracis LethalityPLoS Pathogens, 2008
- Dual Promoters Control Expression of the Bacillus anthracis Virulence Factor AtxAJournal of Bacteriology, 2008
- Virulence Gene Expression Is Independent of ResDE-Regulated Respiration Control inBacillus anthracisJournal of Bacteriology, 2008
- New transposon delivery plasmids for insertional mutagenesis in Bacillus anthracisJournal of Microbiological Methods, 2007
- Negative Regulation ofBacillus anthracisSporulation by the Spo0E Family of PhosphatasesJournal of Bacteriology, 2007
- Opposing effects of histidine phosphorylation regulate the AtxA virulence transcription factor in Bacillus anthracisMolecular Microbiology, 2006
- Sensor Domains Encoded in Bacillus anthracis Virulence Plasmids Prevent Sporulation by Hijacking a Sporulation Sensor Histidine KinaseJournal of Bacteriology, 2006
- Bacillus subtilis Contains Two Small c-Type Cytochromes with Homologous Heme Domains but Different Types of Membrane AnchorsOnline Journal of Public Health Informatics, 1999
- A broad-host-range mobilizable shuttle vector for the construction of transcriptional fusions to β-galactosidase in Gram-positive bacteriaFEMS Microbiology Letters, 1997
- High Affinity Iron Acquisition in Rhizobium Leguminosarum Requires the cycHJKL Operon and the feuPQ Gene Products, which belong to the Family of Two-Component Transcriptional RegulatorsMicrobiology, 1997