Hiding from your hosts: how a cytoplasmic bacterium has engineered its cell envelope to avoid detection

Summary

Obligate intracellular bacteria have evolved under selective pressure to evade detection and subsequent destruction by their cellular hosts. In return they are rewarded with a replicative niche that is rich in nutrients and shielded from extracellular components of the immune system in animals. This mode of interaction has led to one of the most successful symbioses in biology – that between mitochondria/chloroplasts and the modern eukaryotic cell.

In our lab we study the overarching question: how have bacteria modified their fundamental molecular processes of growth and division to adapt to the intracellular niche? In other words, what does it take to transition from a free-living bacterium to an intracellular symbiont or pathogen, and ultimately to an organelle?

We previously showed that certain obligate intracellular bacteria have evolved minimal peptidoglycan cell walls that enable them to grow and divide whilst avoiding activation of the inflammatory response by this immunogenic molecule. We discovered that they lack a group of enzymes previously thought to be essential for peptidoglycan biosynthesis, enabling these bacteria to build a less abundant peptidoglycan wall that is less immunogenic and thus better suited to the intracellular niche.

Project aims

In the current project we will expand our analysis to the evolution of bacterial surfaces to explore how this minimal peptidoglycan layer has impacted the entire bacterial cell envelope. We have realised that certain obligate intracellular bacteria have dispensed with a pathway that is normally strictly essential for bacteria: synthesis of lipid-anchored outer membrane proteins.

The student working on this project will explore how and why certain obligate intracellular bacterial pathogens have modified their outer membrane and the proteins that reside within it, how this has enabled adaptation to the intracellular replicative niche, and the role this plays in pathogenesis.

Contact details

Dr Jeanne Salje - jss53@cam.ac.uk

Opportunities

This project is open to applicants who want to do a:

• PhD