Comparison of the changes in global gene expression of Escherichia coli induced by four bactericidal agents.
DNA microarrays provide a global view of the physiological state of the cell by parallel analysis of the expression levels of all the genes in an organism. The effects of four bactericidal agents on the expression pattern of Escherichia coli MG1655 were assessed. Compounds were chosen on the basis of their different mechanisms of action and included inhibitors of DNA replication and recombination, translation, transcription and cell wall biosynthesis. The addition of rifampin resulted in increased expression of the target, rpoB, as well as several genes involved in nucleotide salvage and purine biosynthesis. The addition of ampicillin resulted in overall changes in gene expression that showed some similarity to changes induced by rifampin. The addition of the antibiotics kanamycin or norfloxacin resulted in the induction of unique gene expression signatures: a heat shock response to kanamycin and an SOS response to norfloxacin. Several genes of unknown function showed expression profiles similar to the genes associated with the SOS or the heat shock response. Thus, these profiles define families of genes with similar expression phenotypes that can be tested for related function.
Johnson & Johnson Pharmaceutical Research & Development, La Jolla, CA 92121, USA. kshaw@prdus.jnj.com
Karen Joy
KJ
Shaw
Nancy
N
Miller
Xuejun
X
Liu
Dmitri
D
Lerner
Jackson
J
Wan
Anton
A
Bittner
Brian J
BJ
Morrow
D000667:Ampicillin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D007612:Kanamycin / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009643:Norfloxacin / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D012293:Rifampin / Q000494:pharmacology; D014158:Transcription, Genetic
D000900:Anti-Bacterial Agents; D029968:Escherichia coli Proteins; D007612:Kanamycin; D000667:Ampicillin; D009643:Norfloxacin; D012293:Rifampin