relA-Independent Amino Acid Starvation Response Network of Streptococcus pyogenes

doi:10.1128/JB.183.24.7354-7364.2001

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Journal of Bacteriology, December 2001, p. 7354-7364, Vol. 183, No. 24
0021-9193/01/$04.00+0 DOI: 10.1128/JB.183.24.7354-7364.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

relA-Independent Amino Acid Starvation Response Network of Streptococcus pyogenes

Kerstin Steiner and Horst Malke^*

Institute for Molecular Biology, Friedrich Schiller University Jena, D-07745 Jena, Germany

Received 2 July 2001/Accepted 24 September 2001

Streptococcus pyogenes (group A streptococcus [GAS]), a multiple-amino-acid-auxotrophic human pathogen, may face starvationfor essential amino acids during various stages of the infectionprocess. Since the response of GAS to such conditions is likelyto influence pathogenetic processes, we set out to identify bytranscriptional analyses genes and operons that are responsiveto amino acid starvation and examined whether functionally meaningfulresponse patterns can be ascertained. We discovered that GAS arecapable of mounting a relA-independent amino acid starvation responsethat involves transcriptional modulation of a wide array of housekeepinggenes as well as accessory and dedicated virulence genes. Housekeepinggenes that were upregulated during starvation of both wild-typeand relA mutant strains included the newly identified T-box membersof the aminoacyl-tRNA synthetase genes, the genes for componentsof the tmRNA-mediated peptide tagging and proteolysis system forabnormal proteins (ssrA, smpB, clpP, and clpC), and the operonsfor the dnaK and groE groups of molecular chaperones. In additionto upregulation of the genes for oligopeptide permease (opp),intracellular peptidase (pepB), and the two-component regulatorcovRS reported previously (K. Steiner and H. Malke, Mol. Microbiol.38:1004-1016, 2000), amino acid starvation stimulated the transcriptionof the growth phase-associated, virulence-regulatory fas operon,the streptolysin S operon (sag), and the gene for autoinducer-2production protein (luxS). A prominent feature of operons exhibitinginternal transcriptional termination (opp, fas, and sag) was starvation-promotedfull-length transcription, a mechanism that improves the efficacyof these systems by increasing the level of coordinate transcriptionof functionally related genes. Based on these results, a regulatorynetwork with feedback mechanisms is proposed that counteractsthe stringent response, links the levels of key rate-limitingenzymes to virulence gene expression, and enables the organismin a dynamic way to take advantage of protein-rich environmentsprovided by its human host. As several of the affected targetgenes are controlled by more than one regulator, fine modulationmay result in accordance with the demands imposed by ecologicallydifferent colonization sites upon the adaptive capacity of thepathogen.

^* Corresponding author. Mailing address: FSU Jena, Institute for Molecular Biology, Winzerlaer Strasse 10, D-07745 Jena, Germany,Phone: 49 3641 657530. Fax: 49 3641 657520. E-mail: hmalke{at}imb-jena.de.

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