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Research Theme

Deinococcus bacteria : Ultra-resistance

Radiation and environmental stresses that damage DNA
Published on 2 March 2020


Scientists (PI) : 

    CNRS, Structural biochemist
Dr Arjan DE  GROOT
    CEA, Geneticist Microbiologist
Our research aims to decipher the molecular mechanisms that confer Deinococcus bacteria an extreme resistance to radiation and stresses that damage DNA (e.g. desiccation, UV, mitomycin C (antibiotic, anti-cancer agent), oxidative stress in general). In this context, our work focuses on the characterization of Deinococcus deserti, a radioresistant bacteria isolated from the Sahara desert, showing original characteristics (compared to the model species Deinococcus radiodurans) highlighted by comparative proteo-genomics (De Groot et al. (2009) PLoS Genet). Exploration of the biodiversity of Deinococcus bacteria, isolated from various environments in the world, is also part of our current studies.

Scientific research theme

Deinococcus bacteria, cocci or rods, present colored colonies on Petri dishes due to the presence of carotenoids. These bacteria tolerate much higher doses of ionizing radiation than most bacteria and human cells (no loss of survival at 5000 Gray (Gy) while a dose of 10 Gy is lethal to humans). This extreme resistance is due to the ability of Deinococcus to reconstitute an intact genome from a genome fragmented by irradiation, including repair of many double-strand breaks that are lethal to most organisms (De Groot et al. (2009) PLoS Genet).

Their secret, discovered step by step in recent years, results from a combination of many factors and finely regulated repair and protection mechanisms (Lim, Jung, Blanchard, De Groot (2019) FEMS Microbiol Rev). However, many mechanisms and functions of new proteins have still to be deciphered.

Elucidating how Deinococci resist radiation may lead to a better understanding of radiation resistance of other organisms or cells (e.g. some cancer cells with increased resistance to radiotherapy), or conversely, to an understanding of why some cells are more radiosensitive than others.

Methods used

The global approaches, of differential proteo-genomics or transcriptomics (RNA sequencing), used in the group allow the discovery of genes/proteins (potentially) involved in radiation resistance. These targets (e.g. genes/proteins radio-induced, involved in DNA repair, specific to Deinococcus or D. deserti) are then characterized by genetics and structural biochemistry.

Research Highlights

  • Accurate annotation of genomes through comparative genomics, proteomics and RNA sequencing. Numerous corrections of prediction errors, including the position of start codons, have enabled the characterization of genes, proteins and regulatory DNA regions playing key roles (De Groot et al. 2009; Baudet et al. 2010; De Groot et al. 2014). The central regulator IrrE, and its 3D structure determination, and the HU protein located in the nucleoid throughout the genome are two examples.
  • Adaptation to the severe climatic conditions of the Sahara desert and specificities of D. deserti. Description of two different RecA proteins and three functional translational DNA polymerases in D. deserti allowing a fine balance between error-free DNA repair and genetic variability necessary to survive in nutrient-poor and UV-exposed conditions, that are the drastic conditions found in hot and dry deserts (Dulermo et al. 2009).
  • Discovery that Deinococcus bacteria mainly use the ancient "leaderless" translation initiation system.
    60% of messenger RNAs in D. deserti are leaderless (i.e. the start codon is not preceded by an untranslated region), including many RNAs encoding peptides. These results provided a new explanation for the origin of the intracellular antioxidant peptide pool that protect proteins against oxidation after irradiation, one of the radioresistance crucial key (De Groot et al. 2014).
  • Characterization of the hyper-compact nucleoid of both D. deserti and D. radiodurans bacteria.
    Low protein diversity within these highly condensed nucleoids, with mainly the presence of HU (Histone-like) protein (Toueille et al. 2013 ; Bouthier de la Tour et al. 2013 ; 2015).
  • Discovery of the original radiation response mechanism in Deinococcus,
    involving a metalloprotease (IrrE) and a transcriptional repressor (DdrO) (Ludanyi et al. 2014; Blanchard et al. 2017; De Groot et al. 2019 and CNRS/INSB highlights). The deciphering of this mechanism is the subject of our main current project that is developed within the ANR NOVOREP and described below.
  • Comprehensive meta-analysis
    of DNA repair systems, defence against oxidative stress, and other radioresistance mechanisms, and their regulation in 11 Deinococcus genomes, showing an unsuspected diversity of these mechanisms within Deinococcus. The exploration of this biodiversity paves the way for new research, new discoveries (Lim, Jung, Blanchard, De Groot (2019) and press release).

Main current project : ANR NOVOREP

Novel radiation response mechanism in Deinococcus

After irradiation, gene expression leading to cell survival is induced via an original SOS-independent way. Two key proteins control this genetic "switch": the metallopeptidase IrrE and the repressor DdrO (Ludanyi et al. 2014; Blanchard et al. 2017), for which we have solved the 3D structure.

IrrE presents an unique combination of two domains: a metallopeptidase domain and a putative sensor domain (Vujicic-Zagar et al. 2009). DdrO consists of a classical HTH-type DNA binding domain and a C-terminal domain that is the target of IrrE and also shows a new fold (De Groot et al. 2019).

Under standard conditions, DdrO binds as a dimer to the two half-sites of a 17bp palindromic motif, therefore inhibiting transcription of the IrrE/DdrO dependent genes. After irradiation/desiccation, DdrO is cleaved by IrrE rapidly inducing the expression of DNA repair genes, genes of unknown function and ddrO itself. Our collaborators at I2BC (Team of F. Confalonieri, Paris Saclay) discovered that the prolonged absence of DdrO induces apoptotic-like cell death in Deinococcus (Devigne et al. 2015). The phenomenon of programmed cell death is poorly characterized in bacteria.

For more information on the radiation response molecular mechanism see the article De Groot et al (2019) and the associated CNRS/INSB highlight.

Further characterisation of this original mechanism is the subject of the ANR NOVOREP ANR-2019-CE12-0010 which started in January 2020.

Collaborators ​
Previous and present PhD students

Rémi Dulermo (2006-2009), Monika Ludanyi (2011-2014), Romaric Magerand (2017-

Collaborators from BIAM, CEA Cadarache
M. Siponen, P. Arnoux, D. Pignol (MEM), D. Lemaire (IPM), P. Rey (PPV)

Collaborators in France and in South Korea
F. Confalonieri, S. Sommer (I2BC, Institut de Biologie Intégrative de la Cellule, Univ. Paris Saclay, France)
P. Roche (CRCM, Inserm, CNRS, Institut Paoli Calmettes, Aix Marseille Univ., France)
J. Armengaud (CEA Marcoule, DRF/JOLIOT, France)
Genoscope (CEA Institut de génomique, Centre National de Séquençage, France)
J.-H. Jung et S. Lim (KAERI, Korea Atomic Energy Research Institute, South Korea)

FEMS Microbiology Reviews 2019 : This meta-analysis was the subject of a press release on October 18, 2018 via the CNRS and the CEA: Nature's unsuspected resources to resist radiation.