Succinate utilisation by Salmonella is inhibited by multiple regulatory systems.

Area of Science:

• Microbiology
• Bacterial Pathogenesis
• Molecular Biology

Background:

• Succinate acts as an immune signal in the gut and macrophages, infection niches for Salmonella Typhimurium.
• Salmonella Typhimurium exhibits slow growth on succinate, a C4-dicarboxylate carbon source, with regulation involving the sigma factor RpoS.
• The precise genetic mechanisms underlying succinate utilization repression in bacteria were not fully understood.

Purpose of the Study:

• To investigate the genetic basis of growth inhibition in Salmonella Typhimurium when utilizing succinate as a sole carbon source.
• To identify novel regulatory systems, beyond RpoS, that control succinate utilization.

Main Methods:

• Employing an experimental evolution approach with Salmonella Typhimurium grown on succinate minimal medium.
• Isolating and analyzing fast-growing mutants to uncover genetic basis of regulation.
• Investigating the roles of specific proteins and regulatory RNAs in succinate metabolism.

Main Results:

• Identified RpoS-independent systems that inhibit succinate utilization.
• Discovered CspC RNA binding protein restricts succinate utilization, antagonized by OxyS sRNA.
• Found IscR represses the DctA transporter, and RbsR is crucial for RpoS-mediated repression.

Conclusions:

• Succinate utilization in Salmonella Typhimurium is controlled by multiple, redundant regulatory systems.
• These findings reveal novel insights into the regulation of central carbon metabolism and its role in niche-specific adaptation.
• The interplay of RpoS-dependent and -independent pathways provides tight control over succinate metabolism.