Simonetta Gribaldo In search of the lost membrane

The envelope, an essential element of bacteria 

In bacteria, the envelope is involved in many functions, such as maintaining physical integrity, absorption and secretion of substances, cell division and movement and communication between cells. Depending on the type of envelope they have, bacteria fall into two categories: those with one membrane (gram-positive or monoderms) and those with two (gram-negative or diderms). 

Many known pathogenic bacteria (such as Escherichia, Pseudomonas and Helicobacter) are diderms. The outer membrane is an additional protective barrier against a hostile environment, including antibiotics. Consequently, a better understanding of the mechanisms involved in building and maintaining the bacterial envelope is a major research challenge with important applications in the fight against infectious diseases.

The ancestor of all bacteria was a diderm 

Simonetta Gribaldo and her team at the Institut Pasteur explore the biodiversity of microorganisms using approaches that focus on major evolutionary shifts in the history of life. Their recent work has challenged a well-established paradigm in microbial evolution by showing that the ancestor of all bacteria was a diderm, and that monoderms evolved successively through loss of the outer membrane. Interestingly, all these losses occurred only in one part of the bacterial phylogenetic tree, known as the Terrabacteria, but never in bacteria belonging to the second part of the tree, the Gracilicutes. 

Given the importance of envelope stability and integrity for bacteria’s life, transitions from diderm to monoderm must have been critical steps in their evolution. How did they come about? Terrabacteria seem to hold the key to this fundamental riddle in evolutionary biology.

What happened to the second membrane?

The first steps towards answering this question will be to fill in the missing genetic information of the various members of Terrabacteria and obtain images of their envelopes. This will help to determine when and how often the outer membrane was lost and identify the key genes involved in the transition. The effect of the genes identified will be tested experimentally in Veillonella parvula, a diderm Terrabacterium found in the human microbiota. Simonetta Gribaldo's laboratory team has cultured this bacteria so that it could be genetically modified and used as a model for the study. 

They will generate mutants with a weakened outer membrane that they will be forced to lose in "accelerated evolution" experiments involving hundreds of generations of bacteria. This will be the first time that a monoderm will have been generated from a diderm in a laboratory. 

Funded by Impulscience^®, the project will shed light on one of the main evolutionary transitions in bacteria, which impacts not only their biodiversity and evolution, but also their adaptation to stress and the disruption of their envelope. What’s more, it will lead to suggesting ways of fighting pathogens by identifying the Achilles' heel that causes bacteria to lose their outer membrane.