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Infection and Immunity, May 2003, p. 2615-2625, Vol. 71, No. 5
0019-9567/03/$08.00+0 DOI: 10.1128/IAI.71.5.2615-2625.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
RegR, a Global LacI/GalR Family Regulator, Modulates Virulence and Competence in Streptococcus pneumoniae
Sabine Chapuy-Regaud,1 A. David Ogunniyi,2 Nicole Diallo,3 Yvette Huet,3 Jean-François Desnottes,3 James C. Paton,2 Sonia Escaich,4 and Marie-Claude Trombe1*
Laboratoire "Interactions et Signalisation Cellulaire: Relation Hôte Pathogène," Institut Louis Bugnard, Centre Hospitalo-Universitaire de Rangueil, Université Paul Sabatier, 31403 Toulouse Cedex,1
Aventis Pharma, 94403 Vitry sur Seine,3
Mutabilis SA, Faculté de Médecine Necker, 75730 Paris Cedex 15, France,4
Department of Molecular Biosciences, Adelaide University, Adelaide, South Australia 5005, Australia2
Received 22 October 2002/
Returned for modification 27 January 2003/
Accepted 11 February 2003
The homolactic and catalase-deficient pathogen Streptococcus pneumoniae is not only tolerant to oxygen but requires the activity of its NADH oxidase, Nox, to develop optimal virulence and competence for genetic transformation. In this work, we show that the global regulator RegR is also involved in these traits. Genetic dissection revealed that RegR regulates competence and the expression of virulence factors, including hyaluronidase. In bacteria grown in vitro, RegR represses hyaluronidase. At neutral pH, it increases adherence to A549 epithelial cells, and at alkaline pH, it acts upstream of the CiaRH two-component signaling system to activate competence. These phenotypes are not associated with changes in antibiotic resistance, central metabolism, and carbohydrate utilization. Although the RegR0 (where 0 indicates the loss of the protein) mutation is sufficient to attenuate experimental virulence of strain 23477 in mice, the introduction of an additional hyl0 (where 0 indicates the loss of function) mutation in the RegR0 strain 23302 dramatically reduces its virulence. This indicates that residual virulence of the RegR0 Hyl+ derivative is due to hyaluronidase and supports the dual role of RegR in virulence. This LacI/GalR regulator, not essential for in vitro growth in rich media, is indeed involved in the adaptive response of the pneumococcus via its control of competence, adherence, and virulence.
* Corresponding author. Mailing address: Lab. Interactions et Signalisation cellulaire: Relation hôte pathogene, EA3036, IFR31 Inst. Louis Bugnard, Centre Hospitalo-Univ. de Rangueil, Université Paul Sabatier, 31403 Toulouse Cedex, France. Phone: 33 (0)5 61 32 29 74. Fax: 33 (0)5 61 32 26 20. E-mail:
trombe{at}cict.fr.
Editor: A. D. O'Brien
Infection and Immunity, May 2003, p. 2615-2625, Vol. 71, No. 5
0019-9567/03/$08.00+0 DOI: 10.1128/IAI.71.5.2615-2625.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
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