Didier  MAZEL
Bacterial Genome Plasticity Unit
Institut Pasteur 25-28 rue du docteur Roux, 75015 Paris
Email: mazel@pasteur.fr
Research area of the Unit
The Unit is working on the mechanisms responsible of the bacterial genome variability, with a special interest for those involved in exogenous gene acquisition – the horizontal gene transfer-, and the rules governing the bacterial genome architecture. The gene exchange model studied in the unit is the integron, a natural genetic engineering system involved in the development and dissemination of antibiotic resistance genes among Gram-negative species, where they are the major source of concerns for the development of multi-resistance. Our different projects deal with the unique recombination properties of integrons, the regulation of the system and its dynamics, as well as the assessment of the available reservoir of adaptive functions (specially in terms of antibiotic resistance) that environmental integrons can provide.
The unit has been one of the most prominent contributors in the understanding of the integron evolution and mechanisms, showing the environmental origin of the integrons and their gene cassettes, demonstrating the existence of a novel recombination process based on single strand DNA recognition, and recently by showing that cassette recruitment was part of the SOS response.

Contribution to the programme

In a majority of case, antibiotic resistance results from gene acquisition through horizontal gene transfer. Current efforts focus on the characterization of accessible reservoirs, but little is still known on the mechanisms, and on the physiological conditions which trigger the emergence of resistance. In most case, we still do not know the ecological niche in which resistance emerges and the dynamics of the transfer. The contribution of the PGB team deals with the understanding of how the complexity of the microbial community influence the emergence of resistance phenotype, both in terms of underlying mechanisms and in terms of dynamics of gene exchange. The group has shown that the SOS response, a general stress response found in most bacterial species, plays a central role in both the gene exchange mechanisms and in the resistance gene cassette recombination in integron. The team develops animal models to test the transfer and recruitment of resistance gene cassettes, and the extent of the connections with the stress response, in vivo. This should allow to better model of resistance development and spread, make more accurate prediction in the future, and appropriately adapt antibiotics treatment practice.

References over the past 5 years
1.      Guerin E*, Cambray G*, Sanchez-Alberola N*, Campoy S, Erill I, Da Re S, Gonzales-Zorn B, Barbé J, Ploy MC and Mazel D. Recombination of integron cassettes is under control of the SOS response. Science (2009), 324(5930):1034 - (*, co–first authors).
2.      Loot C, Bikard D, Rachlin A and Mazel D. Cellular pathways controlling integron cassette site folding. EMBO J. (2010) 29(15): 2623–34
3.      Cambray G, Guérout A-M and Mazel D. Integrons. Annual Review of Genetics (2010) 44:141-66.
4.      Baharoglu Z, Bikard D and Mazel D. Conjugative DNA transfer induces the bacterial SOS response and promotes antibiotic resistance development through integron activation. PLoS Genetics (2010) 6(10): e1001165
5.      Baharoglu Z and Mazel D. Vibrio cholerae triggers SOS and mutagenesis in response to a wide range of antibiotics, a route towards multi-resistance. Antimicrob Agents Chemother. (2011) 55(5):2438-41
6.      Baharoglu Z, Krin E and Mazel D. Transformation-induced SOS regulation and carbon catabolite control of the Vibrio cholerae integron integrase: connecting environment and genome plasticity. J. Bacteriol. (2012) 194(7):1659-67
7.      Val M-E, Skovgaard O, Ducos-Galand M., Bland M.J. and Mazel D. Genome engineering in Vibrio cholerae: A feasible approach to address biological issues. PLoS Genetics (2012) 8(1): e1002472.