Pneumococcal virulence gene expression and host cytokine profiles during pathogenesis of invasive disease

Mahdi, Layla K. and Ogunniyi, Abiodun D. and LeMessurier, Kim S. and Paton, James C. (2008) Pneumococcal virulence gene expression and host cytokine profiles during pathogenesis of invasive disease. Infection and Immunity, 76 (2). pp. 646-657. ISSN 0019-9567

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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.

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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Additional Information: Access to published version in accordance with the copyright policy of the publisher.
Faculty/School / Institute/Centre: Historic - Faculty of Sciences - Department of Biological and Physical Sciences
Date Deposited: 27 Feb 2018 05:09
Last Modified: 27 Feb 2018 05:49
Uncontrolled Keywords: animals; bacterial proteins; blood; brain; colony count,microbial; cytokines; female; gene expression profiling; lung; mice; nasal cavity; pneumococcal infections; reverse transcriptase polymerase chain reaction; virulence factors
Fields of Research : 06 Biological Sciences > 0605 Microbiology > 060501 Bacteriology
06 Biological Sciences > 0605 Microbiology > 060503 Microbial Genetics
11 Medical and Health Sciences > 1108 Medical Microbiology > 110801 Medical Bacteriology
Socio-Economic Objective: E Expanding Knowledge > 97 Expanding Knowledge > 970106 Expanding Knowledge in the Biological Sciences
E Expanding Knowledge > 97 Expanding Knowledge > 970111 Expanding Knowledge in the Medical and Health Sciences
Funding Details:
Identification Number or DOI: 10.1128/IAI.01161-07

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