mgr, a Novel Global Regulator inStaphylococcus aureus

Abstract

The virulence determinants of Staphylococcus aureus are coordinately controlled by several unlinked chromosomal loci. Here, we report the identification of CYL5614, derived from strain Becker, with a mutation that affects the expression of type 8 capsular polysaccharide (CP8), nuclease, alpha-toxin, coagulase, protease, and protein A. This novel locus, named mgr, was linked by transposon Tn917 and mapped by three-factorial transduction crosses. The region containing the mgr locus was cloned and sequenced. Deletion mutagenesis and genetic complementation showed that the locus consisted of one gene, mgrA. Interestingly, mgrA-null mutants exhibited a phenotype opposite to that of CYL5614. This was due to a T-to-C mutation upstream of mgrA that resulted in a four-to eightfold increase in mgrA transcription in strain CYL5614. Thus, these results indicate that mgrA is an activator of CP8 and nuclease but a repressor of alpha-toxin, coagulase, protease, and protein A. In addition, sodium dodecyl sulfate-polyacrylamide gel electrophoresis analyses showed that the mgr locus profoundly affected extracellular protein production, suggesting that the locus may regulate many other genes as well. The translated MgrA protein has a region of significant homology, which includes the helixturn-helix DNA-binding motif, with the Escherichia coli MarR family of transcriptional regulators. Northern slot blot analyses suggested that mgr affected CP8, alpha-toxin, nuclease, and protein A at the transcriptional level.Staphylococcus aureus is an important human pathogen responsible for a wide range of diseases. The pathogenicity of the organism is largely determined by its ability to coordinately produce a plethora of extracellular toxins, enzymes, and surface antigens under various environmental conditions. Recently, several regulatory loci which globally affect the expression of many of these virulence genes have been identified. Among these global regulators, agr and sarA have been studied most extensively.agr is a complex quorum-sensing regulatory system consisting of two divergent transcriptional units, P2 and P3. The P2 operon contains four genes, agrBDCA, of which the agrBD genes are involved in the production and export of an autoinducing peptide. As the cell density increases to a certain level, the accumulated peptide activates, through the two-component system encoded by agrCA, both the P2 and P3 promoters. The P3 operon encodes an RNA effector, RNAIII, which then regulates the target genes (reviewed in reference 21). RNAIII has been shown to control target gene expression largely at the transcriptional level; however, the mechanism is unknown. At the translational level, RNAIII has been shown to regulate alpha-toxin by an antisense mechanism (21).The sarA locus consists of three overlapping transcripts initiating from three different promoters but terminating at a common 3Ј end. All three transcripts contain the major open reading frame (ORF), sarA, within the overlapping region. The SarA protein has been shown to be required ...

CmeR Functions as a Pleiotropic Regulator and Is Required for Optimal Colonization of Campylobacter jejuni In Vivo

“…MgrA contains a typical HTH DNA-binding motif and is a member of the MarR family of transcriptional regulators. Similar to CmeR, MgrA also functions as both a repressor and an activator for various genes in Staphylococcus (16,27,43). A recent DNA microarray study indicated that MgrA affects the expression of 355 genes in multiple functional categories in S. aureus (26).…”

“…In Staphylococcus aureus, the MgrA protein serves a pleiotropic global regulator that modulates the expression of multidrug efflux pumps, type 8 capsular polysaccharide, and extracellular proteins (27,43,44). MgrA contains a typical HTH DNA-binding motif and is a member of the MarR family of transcriptional regulators.…”

Peroxide‐Sensing Transcriptional Regulators in Bacteria

“…Other members of the group include Pseudomonas aeruginosa OspR (63) and MgrA and SarZ in Staphylococcus aureus (54,73). All sense peroxides or other oxidants through the initial oxidation of a sensing cysteine residue (15,16,63).…”

Regulation and characterization of rot transcription in Staphylococcus aureus

“…The expression of many of these virulence genes is coordinately controlled by regulatory loci, such as two-component regulatory systems (agr, saeRS, srrAB and arlSR) and global transcriptional regulators (sarA, sigB, sarA paralogues, tcaRA, etc.) (Arvidson & Tegmark, 2001;Cheung et al, 1992;Cheung & Zhang, 2002;Luong et al, 2003;, 2006aManna et al, 2004;McNamara et al, 2000;McNamara & Bayer, 2005;Novick, 2003;Projan & Novick, 1997;Truong-Bolduc et al, 2003).…”

“…SarA is the first characterized member of the SarA family; others characterized are SarR , SarS (also called SarH1) Tegmark et al, 2000), SarT , Rot (McNamara et al, 2000), SarU (Manna & Cheung, 2003), SarV (Manna et al, 2004), MgrA (Luong et al, 2003;Truong-Bolduc et al, 2003) and SarX (Manna & Cheung, 2006b). The SarA family represents a group of DNA-binding proteins that share homology with each other (20-45 % identity and 45-65 % similarity to SarA protein) as well as with the MarR family of proteins involved in regulating multi-drug resistance in Gram-negative bacteria (Cheung & Zhang, 2002).…”