Succinate utilisation by Salmonella is inhibited by multiple regulatory systems.

Wenner, Nicolas, Zhu, Xiaojun, Rowe, Will PM, Händler, Kristian and Hinton, Jay CD ORCID: 0000-0003-2671-6026 (2024) Succinate utilisation by Salmonella is inhibited by multiple regulatory systems. PLoS genetics, 20 (3). e1011142-e1011142.

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Official URL: http://dx.doi.org/10.1371/journal.pgen.1011142

Abstract

Succinate is a potent immune signalling molecule that is present in the mammalian gut and within macrophages. Both of these infection niches are colonised by the pathogenic bacterium Salmonella enterica serovar Typhimurium during infection. Succinate is a C4-dicarboyxlate that can serve as a source of carbon for bacteria. When succinate is provided as the sole carbon source for in vitro cultivation, Salmonella and other enteric bacteria exhibit a slow growth rate and a long lag phase. This growth inhibition phenomenon was known to involve the sigma factor RpoS, but the genetic basis of the repression of bacterial succinate utilisation was poorly understood. Here, we use an experimental evolution approach to isolate fast-growing mutants during growth of S. Typhimurium on succinate containing minimal medium. Our approach reveals novel RpoS-independent systems that inhibit succinate utilisation. The CspC RNA binding protein restricts succinate utilisation, an inhibition that is antagonised by high levels of the small regulatory RNA (sRNA) OxyS. We discovered that the Fe-S cluster regulatory protein IscR inhibits succinate utilisation by repressing the C4-dicarboyxlate transporter DctA. Furthermore, the ribose operon repressor RbsR is required for the complete RpoS-driven repression of succinate utilisation, suggesting a novel mechanism of RpoS regulation. Our discoveries shed light on the redundant regulatory systems that tightly regulate the utilisation of succinate. We speculate that the control of central carbon metabolism by multiple regulatory systems in Salmonella governs the infection niche-specific utilisation of succinate.

Item Type:	Article
Uncontrolled Keywords:	Animals, Mammals, Salmonella typhimurium, Carbon, Succinic Acid, Succinates, Bacterial Proteins, Sigma Factor, Gene Expression Regulation, Bacterial
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User:	Symplectic Admin
Date Deposited:	13 Mar 2024 09:12
Last Modified:	10 Apr 2024 02:46
DOI:	10.1371/journal.pgen.1011142
Open Access URL:	https://journals.plos.org/plosgenetics/article?id=...
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3179366