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Infection and Immunity, September 2003, p. 4925-4935, Vol. 71, No. 9
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.9.4925-4935.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

ZmpB, a Novel Virulence Factor of Streptococcus pneumoniae That Induces Tumor Necrosis Factor Alpha Production in the Respiratory Tract

C. E. Blue,1 G. K. Paterson,1 A. R. Kerr,1 M. Bergé,2 J. P. Claverys,2 and T. J. Mitchell1*

Division of Infection and Immunity, Institute of Biomedical and Life Sciences, University of Glasgow, Scotland, United Kingdom,1 Laboratoire de Microbiologie et Génétiqué Moléculaire, CNRS-Université Paul Sabatier, Toulouse, France2

Received 17 March 2003/ Returned for modification 1 May 2003/ Accepted 30 May 2003

Inflammation is a prominent feature of Streptococcus pneumoniae infection in both humans and animal models. Indeed, an intense host immune response to infection is thought to contribute significantly to the pathology of pneumococcal pneumonia and meningitis. Previously, induction of the inflammatory response following infection with S. pneumoniae has been attributed to certain cell wall constituents and the toxin pneumolysin. Here we present data implicating a putative zinc metalloprotease, ZmpB, as having a role in inflammation. Null mutations were created in the zmpB gene of the virulent serotype 2 strain D39 and analyzed in a murine model of infection. Isogenic mutants were attenuated in pneumonia and septicemia models of infection, as determined by levels of bacteremia and murine survival. Mutants were not attenuated in colonization of murine airways or lung tissue. Examination of cytokine profiles within the lung tissue revealed significantly lower levels of the proinflammatory cytokine tumor necrosis factor alpha following challenge with the {Delta}zmpB mutant ({Delta}739). These data identify ZmpB as a novel virulence factor capable of inducing inflammation in the lower respiratory tract. The possibility that ZmpB was involved in inhibition of complement activity was examined, but the data indicated that ZmpB does not have a significant effect on this important host defense. The regulation of ZmpB by a two-component system (TCS09) located immediately upstream of the zmpB gene was examined. TCS09 was not required for the expression of zmpB during exponential growth in vitro.

* Corresponding author. Mailing address: Division of Infection and Immunity, Institute of Biomedical and Life Sciences, Joseph Black Building, University of Glasgow, Glasgow G12 8QQ, United Kingdom. Phone: (44) 141 330 3749. Fax: (44) 141 330 3727. E-mail: t.mitchell{at}bio.gla.ac.uk.

Editor: J. N. Weiser

Infection and Immunity, September 2003, p. 4925-4935, Vol. 71, No. 9
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.9.4925-4935.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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