INSA LYON

Bacterial adaptation to environmental changes requires a rapid reorganization of expression pattern of their genome. This adaptive response, which is critical for both bacterial survival and pathogenicity, is mediated by specific transcription factors, DNA supercoiling and global regulators represented by abundant nucleoid-associated-proteins (NAPs), which constrain supercoils and modulate both the chromatin structure and the transcription of numerous genes. Furthermore, the topology of bacterial DNA responds to environmental fluctuations and, together with NAPs, modulates the distribution of the transcription machinery in the genome. The highly compacted bacterial chromosome revealed by electron microscopy on fixed cells was then recognized as a highly dynamic entity only in the 2000s, due to the development of fluorescence microscopy. Chromosome positioning in living cells follows a particular choreography during the cell cycle. While chromosome dynamics coupled to DNA replication/segregation processes is now well understood, the relationship between genome dynamics and expression remains uncleared. Our working hypothesis is that environmental changes modify chromosome conformation, which influence the genomic expression. In the CAGE project, this hypothesis will be tested in plant pathogenic bacteria of the genus Dickeya that cause soft-rot disease in a wide range of plant hosts, including many economically important vegetables such as potato, maize and rice all over the world. The virulence of these bacteria is mainly correlated with their ability to secrete plant cell wall degrading enzymes. To efficiently invade their host, Dickeya have developed complex coordination between virulence gene expression and response to environmental changes. Extended chromosomal domains of coherent transcription, emerging in response to various types of environmental stress encountered during pathogenic growth have been identified. These stress-responsive domains harbour virulence genes and are characterized by distinct couplings of DNA supercoiling sensitivity and response to major NAPs. The CAGE project aims to identify the molecular mechanisms involved in the differential chromosome folding under changing environmental conditions and the repercussion on gene-expression profiles. The study will be developed by (i) correlating transcriptomes with chromosome structure data (high resolution genome contact maps Hi-C and ChIP-Seq) under different environmental conditions relevant to pathogenesis (ii) assessing the impact of the NAPs as well as membrane transertion structures on chromosome dynamics and gene expression (iii) integrating the different results, via computational analyses and simulations, to generate a model coupling chromosome architectures to the expression of Dickeya virulence/adaptive genes. The outcomes of this interdisciplinary project should lead to a new understanding of the role of the chromosome structure in gene expression as well as the roles of DNA structure in bacterial infection which is a highly competitive research field. The importance of crop losses caused yearly by pectinolytic bacteria (within them Dickeya spp.) is a good argument to perform the planned studies in these bacteria. In long term, the implication can be applied for the development of innovative technologies for plant pathogens control. Regarding the economic and social impact, the benefits of this project will contribute towards some of the sustainable development goal such as poverty alleviation and food security. Given the fundamental nature of the project, the expected ramification will be practical applications relevant not only to plant pathogens but also to others, including human pathogens, since pathogenic bacteria use similar strategies to coordinate their virulence programs.

Visual: 
Laboratoires: 
Dates - Duration: 
10/2023 to 09/2026
Funding Institution: 
Contact: 
william.nasser@insa-lyon.fr
Project Leader: 
INSA LYON-MAP
INSA’s scientific leader: 
William NASSER
Subtitle: 
Architecture du chromosome et expression génique chez les bactéries
Funding: 
513417' €'
Chapo: 
Role of the spatial organization of the genome in the control of bacterial infection