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Séminaires Micalis

SeminaireMicalis_Titre_Koszul

Romain KOSZUL

Groupe à 5 ans Régulation spatiale des génomes

Institut Pasteur, Paris

Summary

Genomic analysis of microbial populations in their natural environment remains limited by the difficulty to assemble full genomes of individual species. Consequently, the chromosome organization of microorganisms has been investigated in a few model organisms, but the extent to which the features described can be generalized to other species remains unknown. Using controlled mixes of bacterial and yeast species, we developed meta3C, a high-throughput chromosome conformation capture experiment that allows characterizing individual genomes within a metagenome and their average chromosome organization. Not only can meta3C libraries be used on species with sequenced genomes, but the reads can also be used for the de novo assembly, scaffolding and 3D characterization of unknown genomes, providing an elegant and integrated approach to metagenomic analysis. Focusing on one of these species, Bacillus subtilis, we then combined super-resolution microscopy and high-resolution 3C to unravel the higher-order organization and dynamic rearrangements of its chromosome. Our results shed new light on the general principles underlying chromosome folding, and suggest that sub-megabase chromosomal structures may be evolutionary conserved.

References:

Marbouty et al., “Meta3C unveils the diversity of chromosome organization in microorganisms”, eLife, 2014
Marie-Nelly et al., “High-quality genome (re)assembly from chromosome contact data”, Nature Communications, 2014
Marbouty et al., “3D folding mechanisms of higher-order chromatin domains”, in review

Lundi 02 février 2015 – 14h
Bâtiment 440 - Amphithéâtre J. Poly

Contact

Leyla Slamti – Equipe GME

01 34 65 23 82

SeminaireMicalis_Titre_Jault

Jean-Michel JAULT

UMR5086 CNRS/UCBLyon I, BMSSI-IBCP

7 Passage du Vercors 69367 Lyon cedex 07

Summary

Although the resistance to antibiotic is often multifaceted, multidrug transporters are now recognized as a major player in this mechanism and in particular in the onset of this phenomenon. One family of bacterial multidrug transporters belongs to the ABC (“ATP-Binding Cassette”) superfamily and they expel drugs at the expense of ATP hydrolysis.

In this presentation, I will summarize our effort to understand the functioning mechanism of two prototypical bacterial multidrug ABC transporters: one called BmrA from the model organism Bacillus subtilis and a second one from S/, PatA/PatB, which is involved in the resistance to fluoroquinolones. Both transporters are routinely overexpressed in E. coli, purified in high yield and reconstituted in liposomes or in nanodisks and are characterized by various biophysical and biochemical approaches.

Vendredi 06 février 2015 – 14h
Bâtiment 440 - Amphithéâtre J. Poly

Contact

Delphine Lechardeur – Equipe MicrobAdapt

01 34 65 23 95

SeminaireMicalis_Titre_Nougayrede

Jean-Philippe NOUGAYREDE

CPTP, INRA USC 1360, INSERM UMR 1043

CHU Purpan,  BP 3028, 31024 Toulouse, Cedex 03

Summary

Escherichia coli is a commensal inhabitant of the lower gastrointestinal tract of humans where it is the predominant facultative anaerobic organism. E. coli also belongs to the initial microbiota that colonizes the mammalian gut. Infants are stably colonized by E. coli within a few days after birth. Certain E. coli strains display enhanced ability to cause infection outside the intestinal tract. These extra-intestinal pathogenic E. coli (ExPEC) carry specific genetic determinants or virulence factors that are clustered on genomic islands. We have shown that a subset of ExPEC isolates harbor a genomic island, the pks island, which codes for the production of colibactin, a polyketide-non ribosomal peptide genotoxin. Colibactin production is not restricted to E. coli strains isolated from extra-intestinal infections. Commensal E. coli strains harboring the pks island are ubiquitous in the urban population of industrialized countries. Studies have focused on the impact of colibactin on host cells in vitro and in vivo. The production of colibactin was indeed demonstrated to generate DNA double strand breaks and host cell cycle arrest. Moreover, we recently showed that renewal of the mature intestinal epithelium depends on neonate gut residents and how critical is the synthesis of colibactin by commensal E. coli strain colonizing the newborn. Recent data also indicate that pks+ E. coli strains induce genomic instability and cellular senescence, which could induce carcinogenesis. On the other hand, we have also shown that the pks island is required for the colonic anti-inflammatory properties of a clinically efficient probiotic that is used empirically since almost one century (E. coli Nissle 1917). This Yin-Yang effect of colibactin could result from the production of heterogeneous compounds with different biological activities by the pks island-encoded biosynthetic pathway.

Mercredi 11 mars 2015 – 11h
Bâtiment 440 - Amphithéâtre J. Poly

Contact

Pascale Serror – Equipe CPE

01 34 65 21 66

SeminaireMicalis_Titre_Brun

Yves V. BRUN

Indiana University, Bloomington, IN, USA

Summary

The diversity of shapes of organisms is one of the most fascinating aspects in the field of biology. While bacteria display a myriad of morphologies, the mechanisms that control morphogenesis and the evolution of bacterial morphology are not understood. I will describe the mechanisms that control morphological diversity in species related to Caulobacter crescentus that synthesize appendage-like extensions of the cell envelope at distinct sub-cellular positions. I will show that stepwise evolution of a specific domain of a developmental regulator led to the gain of a new function and localization of this protein, which drove the sequential transition in morphology. Our results indicate that evolution of protein function, co-option, and modularity are key elements in the evolution of bacterial morphology (1). In addition, I will show how evolutionary consideration of the mechanism of growth in the alphaproteobacteria led to the surprising discovery that polar growth, rather than the previously assumed binary fission, is the predominant mode of growth in a large group of the alphaproteobacteria that includes the plant pathogen Agrobacterium tumefaciens and the human pathogen Brucella abortus (2). Finally, I will describe new methods of peptidoglycan labeling that allow the detection of sites of peptidoglycan synthesis in live cells and in real time, and their use to study the mechanisms of peptidoglycan synthesis and to show for the first time that pathogenic Chlamydia have peptidoglycan, ending 50 years of speculation and debate concerning the chlamydial anomaly (3, 4).

References:

1. C. Jiang, P.J.B. Brown, A. Ducret, and Y.V. Brun. 2014. Sequential evolution of bacterial morphology by co-option of a developmental regulator. Nature, 506, 489-93.

2. Brown, P.J.B., M.A. de Pedro, D.T. Kysela, C. Van der Henst, J. Kim, X. De Bolle, C. Fuqua, and Y.V. Brun. 2012. Polar growth in the Alphaproteobacterial Order Rhizobiales. PNAS, 109: 1697-1701.

3. Kuru, E., H.V. Hughes, P.J.B. Brown, E. Hall, S. Tekkam, F. Cava, M.A. de Pedro, Y.V. Brun, and M.S. VanNieuwenhze. 2012. In situ Probing of Newly Synthesized Peptidoglycan in Live Bacteria with Fluorescent D-Amino Acids. Angewandte Chemie, 51(50):12519-23.

4. G. Liechti, E. Kuru, E. Hall, A. Kalinda, Y.V. Brun, M. VanNieuwenhze, and A. Maurelli. 2014. A new metabolic cell wall labeling method reveals peptidoglycan in Chlamydia trachomatis. Nature, 506, 507-10.

Jeudi 12 mars 2015 – Horaire à venir
Bâtiment 440 - Amphithéâtre J. Poly

Contact

Rut Carballido-Lopez – Equipe PROCED

01 34 65 29 55

Rédaction : rs
Date de création : 02 Avril 2011
Mise à jour : 05 Février 2015