Séminaire IBS : Studying Und-P synthesis shows that PG precursor levels regulate cell division in Streptococcus pneumoniae

Par Dr Liselot Dewachter (UCL Louvain, Bruxelles)

Construction of bacterial cell envelope components, including peptidoglycan and teichoic acid precursors, starts in the cytoplasm after which these precursors are flipped across the membrane to be incorporated in their respective cell envelope layer. This transport across the membrane is mediated by the essential lipid carrier undecaprenol-phosphate (Und-P). Yet, the Und-P synthesis pathway is incompletely characterized and the consequences of its depletion on cellular physiology have not been studied in detail. Starting from a genome-wide screen combining CRISPRi-seq with cell sorting, we identified Und-P synthesis as a key regulator of cell size in S. pneumoniae. We further characterize the gene products involved in Und-P production and show that its depletion causes severe cell elongation in S. pneumoniae. We further demonstrate that this cell elongation is due to limited transport of peptidoglycan precursors, which inhibits cell constriction likely by specifically inactivating divisome activity while the elongasome remains active. Finally, we exploit these fundamental research findings for the rational design of a combination therapy that targets both Und-P and peptidoglycan synthesis and is capable of combating antibiotic-resistant strains in vitro.

Hôte : C. Morlot (IBS/Groupe Pneumocoque)