Nitrofurantoin Prompts the Stringent Response in Bacillus subtilis

Abstract

Nitrofurantoin causes the stringent response in Bacillus subtilis. After exposure of a stringent strain to this drug, the intracellular concentrations of guanosine 3'-diphosphate 5'-diphosphate (ppGpp), guanosine 3'-diphosphate 5'-triphosphate (pppGpp) and ATP increased, while that of GTP decreased. In a relaxed strain no accumulation of ppGpp or pppGpp was observed, but both GTP and ATP declined after the addition of nitrofurantoin. Protein synthesis was equally sensitive to nitrofurantoin in both the stringent and relaxed strains, but the drug inhibited RNA accumulation only in the stringent strain, not in the relaxed strain. Nitrofurantoin also caused the accumulation of ppGpp in Escherichia coli and Serratia marcescens.

SB 205952, a novel semisynthetic monic acid analog with at least two modes of action

“…SB 205952 therefore appears to have a second mechanism of action which induces stringency but which is independent of IRS inhibition. Nitrofurantoin and related compounds (27,38) are among the agents known to invoke ppGpp accumulation and stringency, and oxidative inactivation of dihydroxyacid dehydratase has been implicated (38). This enzyme is a key component of the isoleucine biosynthetic pathway in which it functions to convert ␣,␤-dihydroxy-␤-methylvalerate to ␣-keto-␤-methylvalerate (41).…”

Mass Spectrometric Analysis of Drug-induced Changes in Na+ and K+ Contents of Single Bacterial Cells

“…These investigations were performed using Escherichia coli K12 and the drug HN32, a nitrofuran derivative which was shown to be a very powerful antibacterial agent (Seydel & Wempe, 1980) although its specific mechanism of action is not yet known. Only recently it has been shown by Lopez & Fortnagel (1981) that another nitrofuran derivative, nitrofurantoin, has a broad antimicrobial activity and affects the ATP and GTP contents of different bacteria.…”