title: Common changes in global gene expression induced by RNA polymerase inhibitors in Shigella flexneri.
abstract: Characterization of expression profile of organisms in response to antimicrobials provides important information on the potential mechanism of action of the drugs. The special expression signature can be used to predict whether other drugs act on the same target. Here, the common response of Shigella flexneri to two inhibitors of RNA polymerase was examined using gene expression profiling. Consistent with similar effects of the two drugs, the gene expression profiles indicated that responses of the bacteria to these drugs were roughly the same, with 225 genes affected commonly. Of them, 88 were induced and 137 were repressed. Real-time PCR was performed for selected genes to verify the microarray results. Analysis of the expression data revealed that more than 30% of the plasmid-encoded genes on the array were up-regulated by the antibiotics including virF regulon, other virulence-related genes, and genes responsible for plasmid replication, maintenance, and transfer. In addition, some chromosome-encoded genes involved in virulence and genes acquired from horizontal transfer were also significantly up-regulated. However, the expression of genes encoding the beta-subunit of RNA polymerase was increased moderately. The repressed genes include those that code for products associated with the ribosome, citrate cycle, glycolysis, thiamine biosynthesis, purine metabolism, fructose metabolism, mannose metabolism, and cold shock proteins. This study demonstrates that the two antibiotics induce rapid cessation of RNA synthesis resulting in inhibition of translation components. It also indicates that the production of virulence factors involved in intercellular dissemination, tissue invasion and inflammatory destruction may be enhanced through derepressing horizontal transfer genes by the drugs.
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Hua
authors.initials: H
authors.lastname: Fu
authors.forename: Liguo
authors.initials: L
authors.lastname: Liu
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Zhang
authors.forename: Yafang
authors.initials: Y
authors.lastname: Zhu
authors.forename: Lina
authors.initials: L
authors.lastname: Zhao
authors.forename: Junping
authors.initials: J
authors.lastname: Peng
authors.forename: Hongxuan
authors.initials: H
authors.lastname: He
authors.forename: Qi
authors.initials: Q
authors.lastname: Jin
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000378:metabolism*; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors*; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects* / Q000502:physiology; D046228:Microarray Analysis; D014176:Protein Biosynthesis / Q000187:drug effects*; D060888:Real-Time Polymerase Chain Reaction; D012763:Shigella flexneri / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity*; D014774:Virulence
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D012321:DNA-Directed RNA Polymerases