Transcriptional profile induced by furazolidone treatment of Shigella flexneri.
Shigella flexneri is a facultative intracellular pathogen responsible for endemic shigellosis especially in developing countries. Furazolidone, a nitrofuran derivative, is very effective against the infection with S. flexneri. To examine potential effects of furazolidone on this germ, a whole-genome DNA microarray was constructed and transcriptional profiles of the responses to furazolidone were determined. The expressing data revealed adaptive responses of S. flexneri to oxidative stress induced by furazolidone treatment. Iron metabolism was found to be disturbed by furazolidone through derepression of the iron uptake regulon. In addition, energy metabolism, amino acid metabolism, cofactors metabolism, and DNA repair system were also affected by the drug. These data establish a potential for furazolidone to enhance free radical reactions through reductive activation by oxygen-sensitive nitroreductase. Moreover, we provide evidence that furazolidone is able to cause metabolic dysfunction, which cannot always be attributed to oxidative stress, and interactions between reductive metabolites of furazolidone and S. flexneri should be considered.
Fu
Hua
H
State Key Laboratory for Molecular Virology and Genetic Engineering, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 100176, China.
Leng
Wenchuan
W
Wang
Jing
J
Zhang
Wenliang
W
Peng
Junping
J
Wang
Lingling
L
Jin
Qi
Q
D000891:Anti-Infective Agents, Local / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000378:metabolism; D005664:Furazolidone / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D012763:Shigella flexneri / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
D000891:Anti-Infective Agents, Local; D001426:Bacterial Proteins; D005664:Furazolidone