Antoine Danchin
Research interests
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InterestsSynthetic Biology
Publications
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5.50Impact points
Linking selenium biogeochemistry to the sulfur-dependent biological detoxification of arsenic.
Environmental microbiology. 04/2012;
Geochemistry often reveals unexpected (anti)correlations. Arsenic (As) and selenium (Se) are cases in point. We explore the hypothesis that bacteria living in an As-replete environment recruited a biological process involving Se and sulfur to fulfil their need for As detoxification. In analogy with ... [more] Geochemistry often reveals unexpected (anti)correlations. Arsenic (As) and selenium (Se) are cases in point. We explore the hypothesis that bacteria living in an As-replete environment recruited a biological process involving Se and sulfur to fulfil their need for As detoxification. In analogy with the formation of arsenolipids and arsenosugars, which are common non-toxic As metabolites derived from microbial and plant metabolism, we attempt to explain the prevalence of novel sulfur-containing As derivatives, in particular monothioarsenate, in the aqueous environment. Thiolated-As species have been overlooked so far mainly because of the difficulty of their identification. Based on comparative genomics, we propose a scenario where SelD and SelU proteins, commonly used to make selenophosphate and modify transfer RNA, have been recruited to make monothioarsenate, a relatively innocuous arsenical. This hypothesis is discussed in terms of the relative geochemical distribution of Se and As.
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3.76Impact points
Distinct co-evolution patterns of genes associated to bacterial DNA polymerase III DnaE and PolC.
BMC genomics. 02/2012; 13(1):69.
ABSTRACT: BACKGROUND: Bacterial genomes displaying a strong bias between the leading and the lagging strand of DNA replication encode two DNA polymerases III, DnaE and PolC, rather than a single one. Replication is a highly unsymmetrical process, and the presence of two polymerases is therefore not ... [more] ABSTRACT: BACKGROUND: Bacterial genomes displaying a strong bias between the leading and the lagging strand of DNA replication encode two DNA polymerases III, DnaE and PolC, rather than a single one. Replication is a highly unsymmetrical process, and the presence of two polymerases is therefore not unexpected. Using comparative genomics, we explored whether other processes have evolved in parallel with each polymerase. RESULTS: Extending previous in silico heuristics for the analysis of gene co-evolution, we analyzed the function of genes clustering with dnaE and polC. Clusters were highly informative. DnaE co-evolves with the ribosome, the transcription machinery, the core of intermediary metabolism enzymes. It is also connected to the energy-saving enzyme necessary for RNA degradation, polynucleotide phosphorylase. Most of the proteins of this co-evolving set belong to the persistent set in bacterial proteomes, that is fairly ubiquitously distributed. In contrast, PolC co-evolves with RNA degradation enzymes that are present only in the A+T-rich Firmicutes clade, suggesting at least two origins for the degradosome. CONCLUSION: DNA replication involves two machineries, DnaE and PolC. DnaE co-evolves with the core functions of bacterial life. In contrast PolC co-evolves with a set of RNA degradation enzymes that does not derive from the degradosome identified in gamma-Proteobacteria. This suggests that at least two independent RNA degradation pathways existed in the progenote community at the end of the RNA genome world.
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3.03Impact points
Identification of a new nanoRNase in Bartonella.
Microbiology (Reading, England). 01/2012;
In Escherichia coli, only one essential oligoribonuclease (Orn) can degrade oligoribonucleotides of five residues and shorter in length (nanoRNA). In Bacillus subtilis, NrnA and NrnB, which do not have any sequence similarity with Orn, have been identified as functional analogs of Orn. Sequence comp... [more] In Escherichia coli, only one essential oligoribonuclease (Orn) can degrade oligoribonucleotides of five residues and shorter in length (nanoRNA). In Bacillus subtilis, NrnA and NrnB, which do not have any sequence similarity with Orn, have been identified as functional analogs of Orn. Sequence comparisons did not allow identifying orn, nrnA, or nrnB homologues in the genomes of the Chlamydia/Cyanobacteria and Alphaproteobacteria family members. Screening a genomic library from Bartonella birtlesii, a member of the Alphaproteobacteria, for genes that can complement a conditional orn mutant in E. coli, we identified BA0969 (NrnC) as functional analog of Orn. NrnC is well conserved (more than 80% identity) in the Bartonella genomes sequenced to date. Biochemical characterization showed that this protein exhibits oligo RNA degradation activity (nanoRNase activity). Like Orn from E. coli, NrnC is inhibited by micromolar amounts of 3¡¦-phosphoadenosine 5¡¦-phosphate (pAp) in vitro. NrnC is widely present in genomes of Alphaproteobacteria. The knock-down of nrnC decreases significantly the growth ability of Bartonella henselae thus demonstrating the importance of nanoRNase activity in this bacterium.
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5.16Impact points
3'-5'phosphoadenosine phosphate is an inhibitor of Poly(ADP-ribose) Polymerase 1 and a potential mediator of the lithium-dependent inhibition of PARP-1 in vivo.
The Biochemical journal. 01/2012;
3'-5'phosphoadenosine phosphate (pAp) is a by-product of sulfur and lipid metabolism and has been shown to have strong inhibitory properties on RNA catabolism. We report here a new target of pAp, Poly(ADP-ribose) Polymerase 1 (PARP-1), a key enzyme in the detection of DNA single strand break... [more] 3'-5'phosphoadenosine phosphate (pAp) is a by-product of sulfur and lipid metabolism and has been shown to have strong inhibitory properties on RNA catabolism. We report here a new target of pAp, Poly(ADP-ribose) Polymerase 1 (PARP-1), a key enzyme in the detection of DNA single strand breaks. We show that pAp can interact with PARP-1 and inhibit its poly(ADP-ribosyl)ation activity. In vitro, inhibition of PARP-1 was detectable at micromolar concentrations of pAp and altered both PARP-1 automodification and heteromodification of histones. Analysis of the kinetic parameters revealed that pAp acted as a mixed inhibitor that modulates both the KM and the VM of PARP-1. In addition, we showed that upon treatment by lithium, a very potent inhibitor of the enzyme responsible of pAp recycling, HeLa cells exhibited a reduced level of poly(ADP-ribosyl)ation in response to oxidative stress. From these results, we propose that pAp might be a physiological regulator of PARP-1 activity.
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5.20Impact points
Characterization of NrnA homologs from Mycobacterium tuberculosis and Mycoplasma pneumoniae.
RNA (New York, N.Y.). 11/2011; 18(1):155-65.
Processive RNases are unable to degrade efficiently very short oligonucleotides, and they are complemented by specific enzymes, nanoRNases, that assist in this process. We previously identified NrnA (YtqI) from Bacillus subtilis as a bifunctional protein with the ability to degrade nanoRNA (RNA olig... [more] Processive RNases are unable to degrade efficiently very short oligonucleotides, and they are complemented by specific enzymes, nanoRNases, that assist in this process. We previously identified NrnA (YtqI) from Bacillus subtilis as a bifunctional protein with the ability to degrade nanoRNA (RNA oligos ≤5 nucleotides) and to dephosphorylate 3'-phosphoadenosine 5'-phosphate (pAp) to AMP. While the former activity is analogous to that of oligoribonuclease (Orn) from Escherichia coli, the latter corresponds to CysQ. NrnA homologs are widely present in bacterial and archaeal genomes. They are found preferably in genomes that lack Orn or CysQ homologs. Here, we characterize NrnA homologs from important human pathogens, Mpn140 from Mycoplasma pneumoniae, and Rv2837c from Mycobacterium tuberculosis. Like NrnA, these enzymes degrade nanoRNA and dephosphorylate pAp in vitro. However, they show dissimilar preferences for specific nanoRNA substrate lengths. Whereas NrnA prefers RNA 3-mers with a 10-fold higher specific activity compared to 5-mers, Rv2837c shows a preference for nanoRNA of a different length, namely, 2-mers. Mpn140 degrades Cy5-labeled nanoRNA substrates in vitro with activities varying within one order of magnitude as follows: 5-mer>4-mer>3-mer>2-mer. In agreement with these in vitro activities, both Rv2837c and Mpn140 can complement the lack of their functional counterparts in E. coli: CysQ and Orn. The NrnA homolog from Streptococcus mutans, SMU.1297, was previously shown to hydrolyze pAp and to complement an E. coli cysQ mutant. Here, we show that SMU.1297 can complement an E. coli orn(-) mutant, suggesting that having both pAp-phosphatase and nanoRNase activity is a common feature of NrnA homologs.
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47.05Impact points
Open-source genomic analysis of Shiga-toxin-producing E. coli O104:H4.
The New England journal of medicine. 08/2011; 365(8):718-24.
An outbreak caused by Shiga-toxin–producing Escherichia coli O104:H4 occurred in Germany in May and June of 2011, with more than 3000 persons infected. Here, we report a cluster of cases associated with a single family and describe an open-source genomic analysis of an isolate from one member of the... [more] An outbreak caused by Shiga-toxin–producing Escherichia coli O104:H4 occurred in Germany in May and June of 2011, with more than 3000 persons infected. Here, we report a cluster of cases associated with a single family and describe an open-source genomic analysis of an isolate from one member of the family. This analysis involved the use of rapid, bench-top DNA sequencing technology, open-source data release, and prompt crowd-sourced analyses. In less than a week, these studies revealed that the outbreak strain belonged to an enteroaggregative E. coli lineage that had acquired genes for Shiga toxin 2 and for antibiotic resistance.
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6.91Impact points
Life's demons: information and order in biology. What subcellular machines gather and process the information necessary to sustain life?
EMBO reports. 06/2011; 12(6):495-9.
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3.69Impact points
Life in the cold: a proteomic study of cold-repressed proteins in the antarctic bacterium pseudoalteromonas haloplanktis TAC125.
Applied and environmental microbiology. 06/2011; 77(11):3881-3.
The proteomes expressed at 4°C and 18°C by the psychrophilic Antarctic bacterium Pseudoalteromonas haloplanktis were compared using two-dimensional differential in-gel electrophoresis with special reference to proteins repressed by low temperatures. Remarkably, the major cold-repressed proteins, alm... [more] The proteomes expressed at 4°C and 18°C by the psychrophilic Antarctic bacterium Pseudoalteromonas haloplanktis were compared using two-dimensional differential in-gel electrophoresis with special reference to proteins repressed by low temperatures. Remarkably, the major cold-repressed proteins, almost undetectable at 4°C, were heat shock proteins involved in folding assistance.
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The ten grand challenges of synthetic life.
Systems and synthetic biology. 06/2011; 5(1-2):1-9.
The construction of artificial life is one of the main scientific challenges of the Synthetic Biology era. Advances in DNA synthesis and a better understanding of regulatory processes make the goal of constructing the first artificial cell a realistic possibility. This would be both a fundamental sc... [more] The construction of artificial life is one of the main scientific challenges of the Synthetic Biology era. Advances in DNA synthesis and a better understanding of regulatory processes make the goal of constructing the first artificial cell a realistic possibility. This would be both a fundamental scientific milestone and a starting point of a vast range of applications, from biofuel production to drug design. However, several major issues might hamper the objective of achieving an artificial cell. From the bottom-up to the selection-based strategies, this work encompasses the ten grand challenges synthetic biologists will have to be aware of in order to cope with the task of creating life in the lab.
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6.40Impact points
Hydrothermally generated aromatic compounds are consumed by bacteria colonizing in Atlantis II Deep of the Red Sea.
The ISME journal. 04/2011; 5(10):1652-9.
Hydrothermal ecosystems have a wide distribution on Earth and many can be found in the basin of the Red Sea. Production of aromatic compounds occurs in a temperature window of ∼60-150 °C by utilizing organic debris. In the past 50 years, the temperature of the Atlantis II Deep brine pool in the Red ... [more] Hydrothermal ecosystems have a wide distribution on Earth and many can be found in the basin of the Red Sea. Production of aromatic compounds occurs in a temperature window of ∼60-150 °C by utilizing organic debris. In the past 50 years, the temperature of the Atlantis II Deep brine pool in the Red Sea has increased from 56 to 68 °C, whereas the temperature at the nearby Discovery Deep brine pool has remained relatively stable at about 44 °C. In this report, we confirmed the presence of aromatic compounds in the Atlantis II brine pool as expected. The presence of the aromatic compounds might have disturbed the microbes in the Atlantis II. To show shifted microbial communities and their metabolisms, we sequenced the metagenomes of the microbes from both brine pools. Classification based on metareads and the 16S rRNA gene sequences from clones showed a strong divergence of dominant bacterial species between the pools. Bacteria capable of aromatic degradation were present in the Atlantis II brine pool. A comparison of the metabolic pathways showed that several aromatic degradation pathways were significantly enriched in the Atlantis II brine pool, suggesting the presence of aromatic compounds. Pathways utilizing metabolites derived from aromatic degradation were also significantly affected. In the Discovery brine pool, the most abundant genes from the microbes were related to sugar metabolism pathways and DNA synthesis and repair, suggesting a different strategy for the utilization of carbon and energy sources between the Discovery brine pool and the Atlantis II brine pool.
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3.69Impact points
Cytoplasmic and periplasmic proteomic signatures of exponentially growing cells of the psychrophilic bacterium Pseudoalteromonas haloplanktis TAC125.
Applied and environmental microbiology. 02/2011; 77(4):1276-83.
The psychrophilic model bacterium Pseudoalteromonas haloplanktis is characterized by remarkably fast growth rates under low-temperature conditions in a range from 5°C to 20°C. In this study the proteome of cellular compartments, the cytoplasm and periplasm, of P. haloplanktis strain TAC125 was analy... [more] The psychrophilic model bacterium Pseudoalteromonas haloplanktis is characterized by remarkably fast growth rates under low-temperature conditions in a range from 5°C to 20°C. In this study the proteome of cellular compartments, the cytoplasm and periplasm, of P. haloplanktis strain TAC125 was analyzed under exponential growth conditions at a permissive temperature of 16°C. By means of two-dimensional protein gel electrophoresis and mass spectrometry, a first inventory of the most abundant cytoplasmic and periplasmic proteins expressed in a peptone-supplemented minimal medium was established. By this approach major enzymes of the amino acid catabolism of this marine bacterium could be functionally deduced. The cytoplasmic proteome showed a predominance of amino acid degradation pathways and tricarboxylic acid (TCA) cycle enzymes but also the protein synthesis machinery. Furthermore, high levels of cold acclimation and oxidative stress proteins could be detected at this moderate growth temperature. The periplasmic proteome was characterized by a significant abundance of transporters, especially of highly expressed putative TonB-dependent receptors. This high capacity for protein synthesis, efficient amino acid utilization, and substrate transport may contribute to the fast growth rates of the copiotrophic bacterium P. haloplanktis in its natural environments.
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4.41Impact points
Bacterial niche-specific genome expansion is coupled with highly frequent gene disruptions in deep-sea sediments.
PloS one. 01/2011; 6(12):e29149.
The complexity and dynamics of microbial metagenomes may be evaluated by genome size, gene duplication and the disruption rate between lineages. In this study, we pyrosequenced the metagenomes of microbes obtained from the brine and sediment of a deep-sea brine pool in the Red Sea to explore the pos... [more] The complexity and dynamics of microbial metagenomes may be evaluated by genome size, gene duplication and the disruption rate between lineages. In this study, we pyrosequenced the metagenomes of microbes obtained from the brine and sediment of a deep-sea brine pool in the Red Sea to explore the possible genomic adaptations of the microbes in response to environmental changes. The microbes from the brine and sediments (both surface and deep layers) of the Atlantis II Deep brine pool had similar communities whereas the effective genome size varied from 7.4 Mb in the brine to more than 9 Mb in the sediment. This genome expansion in the sediment samples was due to gene duplication as evidenced by enrichment of the homologs. The duplicated genes were highly disrupted, on average by 47.6% and 70% for the surface and deep layers of the Atlantis II Deep sediment samples, respectively. The disruptive effects appeared to be mainly due to point mutations and frameshifts. In contrast, the homologs from the Atlantis II Deep brine sample were highly conserved and they maintained relatively small copy numbers. Likely, the adaptation of the microbes in the sediments was coupled with pseudogenizations and possibly functional diversifications of the paralogs in the expanded genomes. The maintenance of the pseudogenes in the large genomes is discussed.
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2.89Impact points
Decrypting the H-NS-dependent regulatory cascade of acid stress resistance in Escherichia coli.
BMC microbiology. 10/2010; 10:273.
H-NS regulates the acid stress resistance. The present study aimed to characterize the H-NS-dependent cascade governing the acid stress resistance pathways and to define the interplay between the different regulators. We combined mutational, phenotypic and gene expression analyses, to unravel the re... [more] H-NS regulates the acid stress resistance. The present study aimed to characterize the H-NS-dependent cascade governing the acid stress resistance pathways and to define the interplay between the different regulators. We combined mutational, phenotypic and gene expression analyses, to unravel the regulatory hierarchy in acid resistance involving H-NS, RcsB-P/GadE complex, HdfR, CadC, AdiY regulators, and DNA-binding assays to separate direct effects from indirect ones. RcsB-P/GadE regulatory complex, the general direct regulator of glutamate-, arginine- and lysine-dependent acid resistance pathways plays a central role in the regulatory cascade. However, H-NS also directly controls specific regulators of these pathways (e.g. cadC) and genes involved in general stress resistance (hdeAB, hdeD, dps, adiY). Finally, we found that in addition to H-NS and RcsB, a third regulator, HdfR, inversely controls glutamate-dependent acid resistance pathway and motility. H-NS lies near the top of the hierarchy orchestrating acid response centred on RcsB-P/GadE regulatory complex, the general direct regulator of glutamate-, arginine- and lysine-dependent acid resistance pathways.
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5.36Impact points
A path from predation to mutualism.
Molecular microbiology. 09/2010; 77(6):1346-50.
Luminescent bacteria and nematodes associate in a strategy where the bacteria act as virulent pathogens of insects, used as their food supply, while the nematodes graze on them. Upon reaching high density, the bacteria produce light and metabolites that turn the nematodes into hosts permitting them ... [more] Luminescent bacteria and nematodes associate in a strategy where the bacteria act as virulent pathogens of insects, used as their food supply, while the nematodes graze on them. Upon reaching high density, the bacteria produce light and metabolites that turn the nematodes into hosts permitting them to be carried over to further nematode preys. In this issue of Molecular Microbiology, Lango and Clarke show that the corresponding shift in lifestyle is triggered by a metabolic switch closely linked to the tricarboxylic acid cycle, but apparently not by the well-known acetate switch that monitors entry of bacteria into the stationary phase of growth.
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6.91Impact points
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2.15Impact points
RcsB plays a central role in H-NS-dependent regulation of motility and acid stress resistance in Escherichia coli.
Research in microbiology. 05/2010; 161(5):363-71.
In Escherichia coli, hns mutants lack flagellar motility and display an increase in acid stress resistance. Spontaneous phenotypic revertants showed reversion of both H-NS-controlled phenotypes. In the present study, suppressor mutations were identified in the rcsB gene. In addition to RcsA, our exp... [more] In Escherichia coli, hns mutants lack flagellar motility and display an increase in acid stress resistance. Spontaneous phenotypic revertants showed reversion of both H-NS-controlled phenotypes. In the present study, suppressor mutations were identified in the rcsB gene. In addition to RcsA, our experiments establish that H-NS indirectly controlled the RcsB regulator via repression of RcsD. We also show that RcsB(D56E), mimicking phosphorylated RcsB, interacts with GadE to form a RcsB-P/GadE complex, a general direct regulator of glutamate-, arginine- and lysine-dependent acid resistance pathways. In addition, we showed that H-NS positively affects motility via the flhDC master operon repression by RcsB. This substantiates the central role of RcsB in H-NS-mediated control of motility and acid stress resistance.
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6.91Impact points
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5.36Impact points
Proteomics of life at low temperatures: trigger factor is the primary chaperone in the Antarctic bacterium Pseudoalteromonas haloplanktis TAC125.
Molecular microbiology. 02/2010; 76(1):120-32.
The proteomes expressed at 4 degrees C and 18 degrees C by the psychrophilic Antarctic bacterium Pseudoalteromonas haloplanktis have been compared using two-dimensional differential in-gel electrophoresis, showing that translation, protein folding, membrane integrity and anti-oxidant activities are ... [more] The proteomes expressed at 4 degrees C and 18 degrees C by the psychrophilic Antarctic bacterium Pseudoalteromonas haloplanktis have been compared using two-dimensional differential in-gel electrophoresis, showing that translation, protein folding, membrane integrity and anti-oxidant activities are upregulated at 4 degrees C. This proteomic analysis revealed that the trigger factor is the main upregulated protein at low temperature. The trigger factor is the first molecular chaperone interacting with virtually all newly synthesized polypeptides on the ribosome and also possesses a peptidyl-prolyl cis-trans isomerase activity. This suggests that protein folding at low temperatures is a rate-limiting step for bacterial growth in cold environments. It is proposed that the psychrophilic trigger factor rescues the chaperone function as both DnaK and GroEL (the major bacterial chaperones but also heat-shock proteins) are downregulated at 4 degrees C. The recombinant psychrophilic trigger factor is a monomer that displays unusually low conformational stability with a Tm value of 33 degrees C, suggesting that the essential chaperone function requires considerable flexibility and dynamics to compensate for the reduction of molecular motions at freezing temperatures. Its chaperone activity is strongly temperature-dependent and requires near-zero temperature to stably bind a model-unfolded polypeptide.
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8.98Impact points
The Trw type IV secretion system of Bartonella mediates host-specific adhesion to erythrocytes.
PLoS pathogens. 01/2010; 6(6):e1000946.
Bacterial pathogens typically infect only a limited range of hosts; however, the genetic mechanisms governing host-specificity are poorly understood. The alpha-proteobacterial genus Bartonella comprises 21 species that cause host-specific intraerythrocytic bacteremia as hallmark of infection in thei... [more] Bacterial pathogens typically infect only a limited range of hosts; however, the genetic mechanisms governing host-specificity are poorly understood. The alpha-proteobacterial genus Bartonella comprises 21 species that cause host-specific intraerythrocytic bacteremia as hallmark of infection in their respective mammalian reservoirs, including the human-specific pathogens Bartonella quintana and Bartonella bacilliformis that cause trench fever and Oroya fever, respectively. Here, we have identified bacterial factors that mediate host-specific erythrocyte colonization in the mammalian reservoirs. Using mouse-specific Bartonella birtlesii, human-specific Bartonella quintana, cat-specific Bartonella henselae and rat-specific Bartonella tribocorum, we established in vitro adhesion and invasion assays with isolated erythrocytes that fully reproduce the host-specificity of erythrocyte infection as observed in vivo. By signature-tagged mutagenesis of B. birtlesii and mutant selection in a mouse infection model we identified mutants impaired in establishing intraerythrocytic bacteremia. Among 45 abacteremic mutants, five failed to adhere to and invade mouse erythrocytes in vitro. The corresponding genes encode components of the type IV secretion system (T4SS) Trw, demonstrating that this virulence factor laterally acquired by the Bartonella lineage is directly involved in adherence to erythrocytes. Strikingly, ectopic expression of Trw of rat-specific B. tribocorum in cat-specific B. henselae or human-specific B. quintana expanded their host range for erythrocyte infection to rat, demonstrating that Trw mediates host-specific erythrocyte infection. A molecular evolutionary analysis of the trw locus further indicated that the variable, surface-located TrwL and TrwJ might represent the T4SS components that determine host-specificity of erythrocyte parasitism. In conclusion, we show that the laterally acquired Trw T4SS diversified in the Bartonella lineage to facilitate host-restricted adhesion to erythrocytes in a wide range of mammals.
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3.62Impact points
A challenge to vaccinology: living organisms trap information.
Vaccine. 12/2009; 27 Suppl 6:G13-6.
Life couples reproduction of the cell machinery with replication of the genetic program. Both processes are linked to the expression of some information. Over time, reproduction can enhance the information of the machine. We show that accumulation of valuable information results from degradative pro... [more] Life couples reproduction of the cell machinery with replication of the genetic program. Both processes are linked to the expression of some information. Over time, reproduction can enhance the information of the machine. We show that accumulation of valuable information results from degradative processes required to make room for novel entities. Degradation systems act as Maxwell's demons, using energy not to make room per se, but to prevent degradation of what has some functional features. This myopic process will accumulate information, whatever its source, in a ratchet-like manner. The consequence is that genes acquired by horizontal transfer as well as viruses will tend to perpetuate in niches where they are functional, creating recurrent conditions for emergence of diseases.
Following (18)
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Jacques Batut
INRA - Institut National de la Recherche Agronomique -
Rory M Watt
The University of Hong Kong -
Xuhua Xia
Université d'Ottawa -
Fabio Bernini
Università degli Studi di Siena -
Lucien Bettendorff
Université de Liège
