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.