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JAC Advance Access published online on March 5, 2007
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkl560
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© The Author 2007. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Gene expression profiling of the response of Streptococcus pneumoniae to penicillin

P. David Rogers1–5,*, Teresa T. Liu1, Katherine S. Barker1,4, George M. Hilliard5, B. Keith English3,4, Justin Thornton6, Edwin Swiatlo6,7 and Larry S. McDaniel6–8,

1 Department of Pharmacy, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA 2 Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA 3 Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA 4 Children's Foundation Research Center, Le Bonheur Children's Medical Center, Memphis, TN 38103, USA 5 Department of Molecular Sciences, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA 6 Department of Microbiology, University of Mississippi Medical Center, Jackson, MS 39216, USA 7 Division of Infectious Diseases, Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA 8 Department of Surgery, University of Mississippi Medical Center, Jackson, MS 39216, USA

Received 19 October 2006; returned 8 November 2006; revised 2 January 2007; accepted 3 January 2007

* Correspondence address. Children's Foundation Research Center of Memphis, Le Bonheur Children's Medical Center, 50 N. Dunlap Street, Room 304, West Patient Tower, Memphis, TN 38103, USA. Tel: +1-901-572-5387; Fax: +1-901-448-1741; E-mail: drogers{at}utmem.edu

Objectives: The aim of this study was to identify changes in the gene expression profile of Streptococcus pneumoniae in response to a subinhibitory concentration of penicillin in an effort to better understand mechanisms by which this organism copes with this stress.

Methods: S. pneumoniae serotype 2 strain D39 was grown for 1 h in the presence or absence of penicillin at a concentration equivalent to half the MIC (0.03 mg/L). RNA was isolated and gene expression profiles were compared using DNA microarrays. Differential expression of select genes was confirmed by real-time RT–PCR.

Results: A total of 386 genes were found to be responsive to penicillin. Up-regulated genes included those of the ciaR–ciaH operon, luxS, genes encoding cell envelope proteins and genes of the pst locus. Down-regulated genes included genes involved in competence, genes encoding capsular polysaccharide biosynthesis proteins, genes involved in fatty acid chain elongation and genes of the polyamine transporter operon.

Conclusions: Altered expression of these genes reflects a protective response to perturbation of the bacterial cell wall by penicillin. Such genes may represent potential therapeutic targets for enhancing the activity of penicillin against this organism and provide insight into novel mechanisms of penicillin resistance.

Key Words: antibiotics , genomics , microarrays


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