Investigation into the function and glycosylation mechanism of teichoic acids in Listeria monocytogenes

• Applicant: Dr. Jeanine Rismondo
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens ; Metabolism, Biochemistry and Genetics of Microorganisms
• Term: from 2017 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 376428965

Listeria monocytogenes is a human pathogen, which can cause severe infections that are usually treated with high doses of -lactam antibiotics in combination with gentamycin. But despite treatment, infections can be fatal in up to 30% of cases. Therefore, it is important to find new targets for antimicrobials. Teichoic acids, which include wall teichoic acid (WTA) and lipoteichoic acid (LTA), play an important role for cell viability, cell division and virulence. This makes them suitable target for the development of new antimicrobials. LTA and WTA are modified with D-alanine and sugar residues. The alanylation process is well understood, whereas the proteins required in particular for the LTA glycosylation process are either unknown or not well characterized. One aim of this study will be to identify additional proteins involved in the LTA glycosylation process using both genetic as well as computational approaches. Additionally, it has been proposed that the glycosylation process of LTA proceeds through a lipid intermediate. This will be tested as part of this work. In Staphylococcus aureus glycosylation of WTA does not require a lipid intermediate, but there are some hints that in L. monocytogenes the WTA glycosylation proceeds through a lipid intermediate. This hypothesis will be addressed experimentally in this work using in vitro enzyme assays. For the development of an antibiotic, it is crucial to understand the function of the target structure. So far, the cellular function of LTA is not clear and highly discussed. An LTA negative strain L. monocytogenes strain has a severe cell division defect and bacteria are unable to grow at 37°C. After longer incubation at 37°C, viable LTA-negative suppressors strains can be obtained. Characterization of such suppressor strains will help us to shed light on the cellular function of LTA and better understand to why LTA synthesis has an impact on cell division.

• DFG Programme: Research Fellowships
• International Connection: United Kingdom
• Host: Professorin Dr. Angelika Gründling, Ph.D.