Frontier Leaders: How Gram-positive bacteria synthesize lipoteichoic acid and how Staphylococcus aureus manages to survive without it

Frontier Leaders Seminar

Title: How Gram-positive bacteria synthesize lipoteichoic acid and how Staphylococcus aureus manages to survive without it

Speaker: Angelika Grundling

Affiliation: Imperial College of Science, Technology and Medicine

Abstract: 

The cell wall is a vital and multi-functional part of bacterial cells. For Staphylococcus aureus, an important human bacterial pathogen, surface proteins and cell wall polymers are essential for adhesion, colonization and during the infection process. One such cell wall polymer, lipoteichoic acid (LTA), is also crucial for normal bacterial growth and cell division. In S. aureus, LTA is composed of a linear polyglycerolphosphate (PGP) chain that is tethered to the bacterial membrane via the glycolipid diglucosyl-diacylglycerol (Glc2-DAG). The glycerolphosphate (GroP) subunits of LTA are derived from the head group of the membrane lipid phosphatidylglycerol (PG) and the resulting diacylglycerol (DAG) is recycled in the cytoplasm of the cell back to phosphatidylglycerol (PG). It has been estimated that due to LTA synthesis the PG lipid pool is turned over three times per bacterial doubling. The key enzyme required for LTA backbone production is the lipoteichoic acid synthase enzyme LtaS and here it will be described in detail how this enzyme functions. Upon depletion of LtaS and hence the absence of LTA, bacteria cease to grow and an increase in size, a misplacement of division septa and eventual cell lysis is observed. In this work, we describe the isolation and characterization of LTA-deficient S. aureus suppressor strains that regained the ability to grow almost normally in the absence of this cell wall polymer. Using a whole genome sequencing approach, compensatory mutations were identified and revealed that mutations within one gene allow both laboratory and clinical isolates of S. aureus to grow without LTA. Using this suppressor screen approach we identified a novel nucleotide messenger molecule in S. aureus that helps bacteria to cope with extreme cell wall stress and has also a function in controlling cell size in S. aureus.

Angelika Grundling is Senior Lecturer in Molecular Microbiology at Imperial College London and has been awarded an ERC Starting Grant in January 2011 for the project "A functional analysis of Listeria and Staphylococcus lipoteichoic acid” .