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Infection and Immunity, February 2008, p. 646-657, Vol. 76, No. 2
0019-9567/08/$08.00+0     doi:10.1128/IAI.01161-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Pneumococcal Virulence Gene Expression and Host Cytokine Profiles during Pathogenesis of Invasive Disease{triangledown} ,{dagger}

Layla K. Mahdi,{ddagger} Abiodun D. Ogunniyi,{ddagger} Kim S. LeMessurier, and James C. Paton*

School of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia 5005, Australia

Received 20 August 2007/ Returned for modification 6 October 2007/ Accepted 11 November 2007

Pneumococcal disease continues to account for significant morbidity and mortality worldwide. For the development of novel prophylactic and therapeutic strategies against the disease spectrum, a complete understanding of pneumococcal behavior in vivo is necessary. We evaluated the expression patterns of the proven and putative virulence factor genes adcR, cbpA, cbpD, cbpG, cpsA, nanA, pcpA, piaA, ply, psaA, pspA, and spxB after intranasal infection of CD1 mice with serotype 2, 4, and 6A pneumococci by real-time reverse transcription-PCR. Simultaneous gene expression patterns of selected host immunomodulatory molecules, CCL2, CCL5, CD54, CXCL2, interleukin-6, and tomor necrosis factor alpha, were also investigated. We show that pneumococcal virulence genes are differentially expressed in vivo, with some genes demonstrating niche- and serotype-specific differential expression. The in vivo expression patterns could not be attributed to in vitro differences in expression of the genes in transparent and opaque variants of the three strains. The host molecules were significantly upregulated, especially in the lungs, blood, and brains of mice. The pneumococcal-gene expression patterns support their ascribed roles in pathogenesis, providing insight into which protein combinations might be more appropriate as vaccine antigens against invasive disease. This is the first simultaneous comparison of bacterial- and host gene expression in the same animal during pathogenesis. The strategy provides a platform for prospective evaluation of interaction kinetics between invading pneumococci and human patients in culture-positive cases and should be feasible in other infection models.

* Corresponding author. Mailing address: School of Molecular and Biomedical Science, The University of Adelaide, SA 5005, Australia. Phone: 61-8-83035929. Fax: 61-8-83033262. E-mail: james.paton{at}adelaide.edu.au

{triangledown} Published ahead of print on 26 November 2007.

{dagger} Supplemental material for this article may be found at http://iai.asm.org/.

Editor: A. Camilli

{ddagger} L.K.M. and A.D.O. contributed equally to this work.

Infection and Immunity, February 2008, p. 646-657, Vol. 76, No. 2
0019-9567/08/$08.00+0     doi:10.1128/IAI.01161-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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