New proteins that link the regulation of sugar metabolism and peptidoglycan biosynthesis in the Gram-positive pathogen Listeria monocytogenes

• Applicant: Dr. Jeanine Rismondo
• Subject Area: Metabolism, Biochemistry and Genetics of Microorganisms
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 452709177

The human pathogen Listeria monocytogenes is ubiquitously found in nature due to its ability to adjust to and grow in a variety of environmental conditions. L. monocytogenes encodes a multitude of sugar uptake systems, which allows the bacterium to grow in the presence of different carbon sources. However, imported sugars are not only metabolized to support growth and biomass production. Vast amounts are required for the synthesis of key cellular components such as peptidoglycan. How bacteria regulate whether imported sugars are used for catabolic or anabolic processes and how this regulatory mechanisms are influenced by environmental conditions is vastly unknown. The identification of proteins involved in the carbon partitioning will help to understand how bacteria adjust to changing environments. In addition, these proteins could affect the antibiotic resistance or virulence of pathogenic bacteria and thus could be potential targets for the development of new antimicrobial therapies. Recently, we have shown that the absence of the transmembrane domain component EslB of the ABC transporter EslABC results in an impaired cell wall integrity, a cell division defect and a reduced growth in media containing high concentrations of several sugars. So far, it is unknown what the exact cellular function of the ABC transporter EslABC is. I hypothesize that EslABC is a new link between central carbon metabolism, peptidoglycan biosynthesis and cell division. Based on the phenotypes observed for an eslB mutant, it is unlikely that EslABC acts as an importer or exporter. I therefore hypothesize that EslABC could either regulate other proteins via direct protein-protein interaction as described for the ABC transporter FtsEX and affect their activity and/or localization or could be involved in the regulation of carbon flux into central carbon metabolism and peptidoglycan biosynthesis. In the proposed research, we aim to test these hypotheses and unravel the cellular function of EslABC and how its function is linked to central carbon metabolism, cell wall metabolism and cell division in L. monocytogenes. In addition, we plan to determine the structural composition of the transporter and its interactome.

• DFG Programme: Research Grants