DS10 - Défi des autres savoirs

Firmicutes with an outer membrane: toward new models to study the diderm/monoderm cell envelope transition – Fir-OM

Submission summary

The bacterial envelope is one of the oldest and most essential cellular components, being involved in key housekeeping functions, such as physical integrity, cell division, motility, substrate uptake and secretion, and cell-cell communication. It is also a key factor contributing to bacterial pathogenicity, playing roles in bacterial adherence and biofilm formation, virulence factor secretion and resistance to antimicrobials. Yet, bacteria show substantial differences in their cell envelope architectures, among which the most dramatic one is the fact of having one membrane (Gram-positive or monoderm) or two membranes (Gram-negative or diderm). When, how and why such transition between monoderm and diderm cell envelopes occurred is one of the major unanswered questions in Evolutionary Biology. Moreover, a wide diversity of cell envelopes exists across understudied branches of the bacterial tree with no or very little information.

The Firmicutes represent one of the largest bacterial phyla, and are the textbook examples of classical Gram-positive cell envelope architecture with a single membrane and a thick peptidoglycan wall. Surprisingly, two unrelated lineages within the Firmicutes -the Negativicutes and the Halanaerobiales- stain Gram-negative and display typical diderm cell envelopes with an outer membrane (OM) containing LPS, similarly to Escherichia coli, but also having unique characteristics such as an original system to anchor the OM to the cell peptidoglycan. The Negativicutes have been identified from various anaerobic environments, and are particularly abundant components of the human and animal microbiota. Their best-known member is Veillonella, an emerging and understudied human pathogen responsible for periodontitis and other systemic infections. The Halanaerobiales are a poorly studied group of halophilic/halotolerant/thermotolerant, strict anaerobic Firmicutes of industrial/biotechnological interest. The existence of lineages presenting a diderm phenotype that are phylogenetically embedded within monoderm Firmicute clades makes them fantastic experimental models to test different scenarios on the emergence of monoderm and diderm architectures during the evolution of bacteria. However, very little data is available on the cell envelope characteristics of Negativicutes, and no experimental characterization has been done on the Halanaerobiales.

With the Fir-OM project, we aim at a pioneering investigation of these two largely understudied branches of the Firmicutes through an original combination of experimental (phenotype, microscopy, cell envelope proteomics, genetics) and in silico (genome sequencing, phylogenomics, comparative genomics) approaches. We will expand the genomic coverage for both lineages through targeted sequencing of representative members. We will obtain the first cell envelope proteomic analysis for Halanaerobiales and additional Negativicutes. These results will be associated with a global phylum-level phylogenomic analysis to understand the diversity, origin, and evolutionary history of the atypical cell envelopes of diderm firmicutes, their relationships with those of their closest monoderm relatives as well those of the other bacterial diderm phyla, and discover novel components and cellular processes linked to their function.

Our results will have impact on different issues. We will pioneer a novel research line on two largely understudied bacterial clades, one with evident involvement in human health, but whose underlying mechanisms remain to uncover. We will provide data on a novel type of bacterial cell envelope, sensibly expanding knowledge on one of the oldest cellular components. We will test the hypothesis that diderm cell envelopes are ancestral and were lost multiple times independently in the Firmicutes, or alternatively that they can be acquired through horizontal gene transfer. In both cases, we will provide an important change in paradigm for Microbiology.

Project coordination

Simonetta Gribaldo (INSTITUT PASTEUR -Biologie Moléculaire du Gene chez les Extremophiles)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.


IP-BMGE INSTITUT PASTEUR -Biologie Moléculaire du Gene chez les Extremophiles
IP-GDB INSTITUT PASTEUR - Génétique des Biofilms

Help of the ANR 367,756 euros
Beginning and duration of the scientific project: December 2016 - 36 Months

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