International Journal of Medical Microbiology 297 (2007) 513–523 Transcriptome analyses extend understanding of Streptococcus pyogenes regulatory mechanisms and behavior toward immunomodulatory substances Catur Riani 1 , Kerstin Standar 1 , Somboon Srimuang 2 , Cordula Lembke, Bernd Kreikemeyer, Andreas Podbielski à Department of Medical Microbiology, Virology, and Hygiene, University Hospital Rostock, Schillingallee 70, D-18057 Rostock, Germany Received 30 August 2006; received in revised form 2 April 2007; accepted 4 April 2007 Abstract The recent genome sequencing of several Streptococcus pyogenes serotype strains allowed the design of corresponding DNA microarrays and their usage for specific transcriptome analyses. In the present study, we employed transcriptomics together with functional tests to investigate the impact of the CiaH sensor gene of the CiaRH two-component regulator on gene expression and virulence traits of serotype M49 S. pyogenes strains CS101 and 591. In parallel, we studied the effects of the immunostimulatory substance Luivac s on the serotype M49 S. pyogenes transcriptome and several biological features of serotype M1, M2, M3, M6, M18, and M49 S. pyogenes strains. Overall, the transcriptome analyses allowed a swift identification of differences in transcript abundance apparently associated with the observed strain-specific changes in matrix protein binding, eukaryotic cell interactions, or biofilm formation of the ciaH mutants and of wild-type strains exposed to a commercially available substance used for preventing upper respiratory tract infections. r 2007 Elsevier GmbH. All rights reserved. Keywords: Streptococcus pyogenes; Transcriptomics; Cia regulator; Luivac immunostimulator; Virulence Introduction Purulent infections of the upper respiratory tract and skin caused by Streptococcus pyogenes (group A streptococci, GAS) are extremely frequent, with about 730 million yearly incidences worldwide. In addition, these bacteria trigger 940,000 yearly cases of post- infection sequelae and 660,000 yearly cases of life- threatening infections (Carapetis et al., 2005). Unlike for other similarly or less important pathogens, vaccination against S. pyogenes is currently not available. This situation stimulated a substantial funding primarily in the USA for sequencing the genomes of several S. pyogenes serotype strains to facilitate the understanding of crucial pathogenicity traits of these bacteria and to identify promising targets for vaccine development. As a consequence, presently there are 12 strains of 8 ARTICLE IN PRESS www.elsevier.de/ijmm 1438-4221/$ - see front matter r 2007 Elsevier GmbH. All rights reserved. doi:10.1016/j.ijmm.2007.04.005 à Corresponding author. Tel.: +49 38 1494 5900; fax: +49 38 1494 5902. E-mail address: andreas.podbielski@med.uni-rostock.de (A. Podbielski). 1 Both authors contributed equally to this publication. 2 Present address: Research Ctr., Ramathibodi Hospital, Mahidol University, Rama 6 Road, Bangkok 10400, Thailand.