Streptomyces: a screening tool for bacterial cell division inhibitors

Area of Science:

• Microbiology
• Cell Biology
• Bacterial Genetics

Background:

• Cell division is crucial for spore formation in filamentous streptomycetes but not for their survival.
• The bacterial divisome, responsible for cell division, shows similarities across prokaryotes, suggesting conserved mechanisms.
• Sporulation inhibitors in streptomycetes might target conserved cell division processes applicable to other bacteria.

Purpose of the Study:

• To investigate if chemical inhibitors of streptomycetes sporulation can impede cell division in rod-shaped bacteria.
• To identify compounds that disrupt cell division and explore their mechanisms of action.
• To evaluate the potential of these compounds as broad-spectrum cell division inhibitors.

Main Methods:

• Screening of 196 compounds known to inhibit sporulation in Streptomyces coelicolor.
• Testing the effect of these compounds on cell division and growth morphology in Bacillus subtilis.
• Analyzing the mechanisms of action, including DNA damage and SOS response activation.

Main Results:

• Nineteen of the tested compounds induced filamentous growth in Bacillus subtilis, indicating impaired cell division.
• One compound acted as a DNA-damaging agent, inhibiting cell division via the SOS response.
• Eighteen compounds functioned independently of known stress responses, potentially targeting the divisome directly.
• Three specific compounds (Fil-1, Fil-2, Fil-3) caused distinct cell division defects and blocked sporulation in B. subtilis.

Conclusions:

• Compounds inhibiting sporulation in streptomycetes can effectively inhibit cell division in other bacterial species.
• The study identified novel chemical inhibitors of bacterial cell division, with some acting through distinct mechanisms.
• These findings offer new strategies for developing broad-spectrum antibacterial agents targeting the conserved bacterial divisome.