Regulation of Arginine Acquisition and Virulence Gene Expression in the Human Pathogen Streptococcus pneumoniae by Transcription Regulators ArgR1 and AhrC

In this study, we investigated for the first time the transcriptional response of the human pathogen Streptococcus pneumoniae to fluctuating concentrations of arginine, an essential amino acid for this bacterium. By means of DNA microarray analyses, several operons and genes were found, the expressi...

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Bibliographic Details
Published in:The Journal of biological chemistry 2011-12, Vol.286 (52), p.44594-44605
Main Authors: Kloosterman, Tomas G., Kuipers, Oscar P.
Format: Article
Language:English
Subjects:
Amino Acid Transport Systems - biosynthesis
Amino Acid Transport Systems - genetics
Arginine
Arginine - genetics
Arginine - metabolism
Bacteria
Bacterial Proteins - genetics
Bacterial Proteins - metabolism
Gene Expression Regulation, Bacterial - physiology
Gene Regulation
Human Pathogen
Humans
Nitrogen Metabolism
Oligonucleotide Array Sequence Analysis
Streptococcus
Streptococcus pneumoniae
Streptococcus pneumoniae - genetics
Streptococcus pneumoniae - metabolism
Streptococcus pneumoniae - pathogenicity
Transcription Factors - genetics
Transcription Factors - metabolism
Transcriptomics
Virulence Factors - biosynthesis
Virulence Factors - genetics
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Summary:In this study, we investigated for the first time the transcriptional response of the human pathogen Streptococcus pneumoniae to fluctuating concentrations of arginine, an essential amino acid for this bacterium. By means of DNA microarray analyses, several operons and genes were found, the expression of which was affected by the concentration of arginine in the medium. Five of the identified operons were demonstrated to be directly repressed in the presence of high arginine concentrations via the concerted action of the ArgR-type regulators ArgR1 and AhrC. These ArgR1/AhrC targets encompass the putative amino acid transport genes artPQ, abpA, abpB, and aapA; the arginine biosynthetic genes argGH; and the virulence genes aliB and lmB/adcAII-phtD encoding an oligopeptide-binding lipoprotein and cell surface Zn2+-scavenging units, respectively. In addition, the data indicate that three of the amino acid transport genes encode an arginine ATP-binding cassette transporter unit required for efficient growth during arginine limitation. Instead of regulating arginine biosynthetic and catabolic genes as has been reported for other Gram-positive bacteria, our findings suggest that the physiological function of ArgR1/AhrC in S. pneumoniae is to ensure optimal uptake of arginine from the surrounding milieu. Arginine is a key amino acid in cellular metabolism in bacteria. ArgR1 and AhrC mediate arginine-dependent expression of arginine acquisition and virulence genes in the human pathogen Streptococcus pneumoniae. Arginine regulation in S. pneumoniae significantly differs from that in other model bacteria. Understanding metabolic regulation increases insights into the molecular pathogenesis of S. pneumoniae.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M111.295832