Our project has led to a series of important findings which have been published in high impact journals such as Science, Nature Microbiology, Cell Host and Microbe, Nature Communications, PNAS, EMBO Reports, Cell Reports… and presented to many meetings in both Europe and the US (e.g. Gordon conferences, FEMS general meeting). We published several reviews in prestigious journals (Annual Reviews of Microbiology, Nature Microbiology Reviews…). Two patents have been deposited.
For our objective 1 which concerns the bacterium itself.
By using an N-terminomic approach to identify all the N-terminal peptides and all the start codons of the proteins encoded in the genome when bacteria are grown in three different conditions, we have discovered a never reported mini protein present in many firmicutes and showed how a bacterium by using this mini protein can relay an extracellular stress to the intracellular nanomachine called the stressosome and coordinate the expression of a series of genes involved in the stress response. In addition, we have determined the detailed structure of the Listeria stressosome.
We have identified the first secreted bacterial RNA binding protein which during infection binds and activates RIG-I and leads to the production of type I interferon.
We have identified in the Listeria strains which are responsible for epidemics, a bacteriocin which acts in the gut and favors infection. There are similar proteins in other bacteria, including streptococci. We have identified another bacteriocin which can target Prevotella copri in the gut and modulate infection.
We have discovered two previously unknown antibiotic resistance genes in Listeria, one of them is acting using a novel mechanism , i.e. ribosome splitting.
For our objective 2 which concerns the cell organelles during infection.
We have discovered that septins, (small GTPases able to form filaments and rings) play a critical role in mitochondrial dynamics. Mitochondrial dynamics is necessary for infection. Fragmentation is induced by the bacterial protein listeriolysin O (LLO). By analyzing the proteins present at the mitochondria during infection of cultures cells with the wild type or with the LLO mutant, we have discovered a role for Mic10, a subunit of the MICOS complex in the non-classical and Drp1-independent transient mitochondrial fragmentation occurring during infection.
For our objective 3 which concerns transcription in the infected host and the transcripts of the host.
We have discovered that for histone H3K18 deacetylation and the ensuing gene repression necessary for efficient infection, the deacetylase SIRT2 is dephosphorylated on Ser25, an event allowing its association to chromatin after its translocation to the nucleus. In addition, we have shown that the epitranscriptomic mark N6 adenosine methylation on intestinal mRNA, is affected by the intestinal microbiota. Moreover, the microbiota also affects the N6A methylation in the liver, revealing a new layer of regulation induced by the gut microbiota.
