Nitrofurantoin prompts the stringent response in Bacillus subtilis

Area of Science:

• Microbiology
• Bacterial Physiology
• Molecular Biology

Background:

• The stringent response is a global regulatory mechanism in bacteria that conserves resources under stress.
• Nitrofurantoin is an antibiotic used to treat urinary tract infections.
• Understanding the molecular mechanisms of antibiotic action is crucial for combating resistance.

Purpose of the Study:

• To investigate the effect of nitrofurantoin on the stringent response in Bacillus subtilis.
• To elucidate the role of intracellular nucleotide changes in nitrofurantoin's mechanism of action.
• To compare the drug's effects on stringent and relaxed bacterial strains.

Main Methods:

• Exposure of Bacillus subtilis stringent and relaxed strains to nitrofurantoin.
• Measurement of intracellular nucleotide concentrations (ppGpp, pppGpp, ATP, GTP).
• Assessment of protein synthesis and RNA accumulation rates.

Main Results:

• Nitrofurantoin induced the stringent response in Bacillus subtilis, increasing ppGpp and pppGpp levels in stringent strains.
• Stringent strains showed decreased GTP but increased ATP, while relaxed strains had decreased GTP and ATP.
• Protein synthesis was inhibited similarly in both strains, but RNA accumulation was only affected in stringent strains.
• Nitrofurantoin also induced ppGpp accumulation in Escherichia coli and Serratia marcescens.

Conclusions:

• Nitrofurantoin elicits the stringent response in Bacillus subtilis, mediated by alterations in guanosine polyphosphates.
• The stringent response is key to nitrofurantoin's inhibition of RNA accumulation, but not protein synthesis.
• Nitrofurantoin's ability to induce the stringent response is conserved across different bacterial species.