Transcription profiling-based identification of Staphylococcus aureus genes regulated by the agr and/or sarA loci.
The advent of transcription profiling technologies has provided researchers with an unprecedented ability to study biological processes. Accordingly, a custom-made Affymetrix GeneChip, constituting >86% of the Staphylococcus aureus genome, was used to identify open reading frames that are regulated by agr and/or SarA, the two best-studied regulators of the organism's virulence response. RNA extracted from wild-type cells and agr, sarA, and agr sarA mutant cells in the early-, mid-, and late-log and stationary phases of growth was analyzed. Open reading frames with transcription patterns expected of genes either up- or downregulated in an agr- and/or SarA-dependent manner were identified. Oligonucleotide microarray and Northern blot analyses confirmed that the transcription of several known virulence genes, including hla (alpha-toxin) and spa (protein A), is regulated by each effector and provided insights about the regulatory cascades involved in both alpha-hemolysin and protein A expression. Several putative virulence factors were also identified as regulated by agr and/or SarA. In addition, genes that are involved in several biological processes but which are difficult to reconcile as playing a direct role in the organism's pathogenesis also appeared to be regulated by each effector, suggesting that products of both the agr and the sarA locus are more-global transcription regulators than previously realized.
Dunman
P M
PM
Infectious Diseases, Wyeth-Ayerst Research, Pearl River, New York 10965, USA.
Murphy
E
E
Haney
S
S
Palacios
D
D
Tucker-Kellogg
G
G
Wu
S
S
Brown
E L
EL
Zagursky
R J
RJ
Shlaes
D
D
Projan
S J
SJ
D001426:Bacterial Proteins / Q000378:metabolism*; D001427:Bacterial Toxins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015536:Down-Regulation; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D006460:Hemolysin Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D016366:Open Reading Frames; D013205:Staphylococcal Protein A / Q000235:genetics; D013211:Staphylococcus aureus / Q000235:genetics* / Q000472:pathogenicity; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism*; D015854:Up-Regulation; D014774:Virulence / Q000235:genetics
C095698:Agr protein, Staphylococcus aureus; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004268:DNA-Binding Proteins; D006460:Hemolysin Proteins; C088021:SarA protein, bacterial; D013205:Staphylococcal Protein A; D015534:Trans-Activators; D014157:Transcription Factors; C021091:staphylococcal alpha-toxin