One ligand, two regulators and three binding sites: How KDPG controls primary carbon metabolism in Pseudomonas

Campilongo, Rosaria, Fung, Rowena K. Y., Little, Richard H., Grenga, Lucia, Trampari, Eleftheria, Pepe, Simona, Chandra, Govind, Stevenson, Clare E. M., Roncarati, Davide and Malone, Jacob G. ORCID: (2017) One ligand, two regulators and three binding sites: How KDPG controls primary carbon metabolism in Pseudomonas. PLoS Genetics, 13 (6). ISSN 1553-7404

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Effective regulation of primary carbon metabolism is critically important for bacteria to successfully adapt to different environments. We have identified an uncharacterised transcriptional regulator; RccR, that controls this process in response to carbon source availability. Disruption of rccR in the plant-associated microbe Pseudomonas fluorescens inhibits growth in defined media, and compromises its ability to colonise the wheat rhizosphere. Structurally, RccR is almost identical to the Entner-Doudoroff (ED) pathway regulator HexR, and both proteins are controlled by the same ED-intermediate; 2-keto-3-deoxy-6-phosphogluconate (KDPG). Despite these similarities, HexR and RccR control entirely different aspects of primary metabolism, with RccR regulating pyruvate metabolism (aceEF), the glyoxylate shunt (aceA, glcB, pntAA) and gluconeogenesis (pckA, gap). RccR displays complex and unusual regulatory behaviour; switching repression between the pyruvate metabolism and glyoxylate shunt/gluconeogenesis loci depending on the available carbon source. This regulatory complexity is enabled by two distinct pseudo-palindromic binding sites, differing only in the length of their linker regions, with KDPG binding increasing affinity for the 28 bp aceA binding site but decreasing affinity for the 15 bp aceE site. Thus, RccR is able to simultaneously suppress and activate gene expression in response to carbon source availability. Together, the RccR and HexR regulators enable the rapid coordination of multiple aspects of primary carbon metabolism, in response to levels of a single key intermediate.

Item Type: Article
Faculty \ School: Faculty of Science > School of Biological Sciences
Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups: Faculty of Science > Research Groups > Molecular Microbiology
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Depositing User: Pure Connector
Date Deposited: 04 Jul 2017 05:06
Last Modified: 22 Oct 2022 02:51
DOI: 10.1371/journal.pgen.1006839


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