Gene expression profiling of the response of Streptococcus pneumoniae to penicillin.
OBJECTIVE
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.
Rogers
P David
PD
Department of Pharmacy, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA. drogers@utmem.edu
Liu
Teresa T
TT
Barker
Katherine S
KS
Hilliard
George M
GM
English
B Keith
BK
Thornton
Justin
J
Swiatlo
Edwin
E
McDaniel
Larry S
LS
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D003627:Data Interpretation, Statistical; D015536:Down-Regulation / Q000187:drug effects; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D005798:Genes, Bacterial / Q000187:drug effects*; D020411:Oligonucleotide Array Sequence Analysis; D010403:Penicillin Resistance / Q000235:genetics; D010406:Penicillins / Q000494:pharmacology*; D012329:RNA, Bacterial / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000235:genetics*; D015854:Up-Regulation / Q000187:drug effects
D000900:Anti-Bacterial Agents; D010406:Penicillins; D012329:RNA, Bacterial; D012333:RNA, Messenger