Biomedical subjects

Emmanuel Talla

Publications and source records attributed to Emmanuel Talla.

11 recordsLinked to original sources

PubMed2026

A conserved partner-switching system controls terminal differentiation in multicellular cyanobacteria.

UNLABELLED: Canonical partner-switching systems (PSSs) regulate sigma factor activity through reversible phosphorylation, but their established roles have been largely limited to stress responses and sporulation in Firmicutes. Whether this regulatory mechanism also controls developmental cell fate decisions in other bacterial phyla has remained unknown. Here, we identify a canonical PSS that governs heterocyst differentiation in the multicellular cyanobacterium Anabaena sp. PCC 7120. This system comprises the anti-sigma factor All2284 (NfsS) and the anti-anti-sigma factor All2283 (NfsR). Structural predictions and biochemical assays showed that NfsS phosphorylates NfsR on a conserved serine residue, whereas bacterial two-hybrid and co-purification assays demonstrated that NfsS binds the developmental sigma factors SigC and SigE. Deletion of nfsR abolished heterocyst formation and diazotrophic growth, and transcriptomic analysis revealed broad failure to induce late heterocyst genes, including nitrogen fixation functions such as nifHDK and fdxH. Phylum-wide comparative genomics further showed that PSS genes and putative functional clusters are strongly enriched in filamentous and heterocyst-forming taxa, indicating an association between the expansion of these signaling modules and the emergence of multicellularity and developmental specialization. Together, these findings establish a PSS as a direct regulator of terminal cell differentiation in a gram-negative bacterium and reveal partner switching as a conserved regulatory principle linking environmental signaling to developmental fate in a major bacterial phylum. IMPORTANCE: While partner-switching systems are classically associated with stress responses and sporulation control in Firmicutes, whether this regulatory logic governs developmental decisions in other bacterial phyla has remained unknown. Here, we establish that a related partner-switching mechanism operates in a distinct bacterial lineage, the cyanobacteria, where it controls a major developmental transition involving terminal cell differentiation. Specifically, we show that a phosphorylation-dependent checkpoint involving the anti-sigma factor NfsS and the anti-anti-sigma factor NfsR directly regulates heterocyst formation. Disruption of this switch abolishes cell differentiation and diazotrophic growth, revealing that this system is an obligate gatekeeper for terminal differentiation. Conceptually, these findings substantially extend the known functional repertoire of partner-switching circuits: rather than controlling stress adaptation or spore dormancy, this module has been co-opted to govern a complex, multicellular developmental program in an organism that underpins global carbon and nitrogen cycles. This work, therefore, establishes a new paradigm for phosphorylation-based control of developmental sigma factors and provides a tractable model for dissecting how conserved signaling modules are rewired to drive lineage-specific innovations across the bacterial domain.

cell differentiation↗

PubMed2005

The complete mitochondrial genome of the yeast Kluyveromyces thermotolerans.

We report here the complete nucleotide sequence of the 23.5-kb mitochondrial genome from the yeast Kluyveromyces thermotolerans. It encodes, all on the same DNA strand, three subunits of cytochrome oxidase (COX1, COX2 and COX3), three subunits of ATP synthetase (ATP6, ATP8 and ATP9), the apocytochrome b (COB), the ribosomal protein VAR1, 24 tRNAs, the small and large ribosomal RNAs, and the RNA subunit of RNase P. Three intronic ORFs are present within the COX1 gene group I introns. The K. thermotolerans mitochondrial genome is very similar to the Candida glabrata mitochondrial genome, as judged from clusters of gene order, gene transcription units and sequence similarities. Interestingly, the predicted secondary structure of the abnormal tRNAThr1 contains 10 nucleotides in its anticodon loop. This sequence is available under EMBL Accession No. AJ634268.

Base Sequence↗

PubMed2004

Large-scale exploration of growth inhibition caused by overexpression of genomic fragments in Saccharomyces cerevisiae.

We have screened the genome of Saccharomyces cerevisiae for fragments that confer a growth-retardation phenotype when overexpressed in a multicopy plasmid with a tetracycline-regulatable (Tet-off) promoter. We selected 714 such fragments with a mean size of 700 base-pairs out of around 84,000 clones tested. These include 493 in-frame open reading frame fragments corresponding to 454 distinct genes (of which 91 are of unknown function), and 162 out-of-frame, antisense and intergenic genomic fragments, representing the largest collection of toxic inserts published so far in yeast.

Cloning, Molecular↗

PubMed2004

Genome evolution in yeasts.

Identifying the mechanisms of eukaryotic genome evolution by comparative genomics is often complicated by the multiplicity of events that have taken place throughout the history of individual lineages, leaving only distorted and superimposed traces in the genome of each living organism. The hemiascomycete yeasts, with their compact genomes, similar lifestyle and distinct sexual and physiological properties, provide a unique opportunity to explore such mechanisms. We present here the complete, assembled genome sequences of four yeast species, selected to represent a broad evolutionary range within a single eukaryotic phylum, that after analysis proved to be molecularly as diverse as the entire phylum of chordates. A total of approximately 24,200 novel genes were identified, the translation products of which were classified together with Saccharomyces cerevisiae proteins into about 4,700 families, forming the basis for interspecific comparisons. Analysis of chromosome maps and genome redundancies reveal that the different yeast lineages have evolved through a marked interplay between several distinct molecular mechanisms, including tandem gene repeat formation, segmental duplication, a massive genome duplication and extensive gene loss.

Chromosomes, Fungal↗

PubMed2004

Gene relics in the genome of the yeast Saccharomyces cerevisiae.

There is increasing evidence that DNA duplication is a common and ongoing process that plays a major role in molecular evolution of genomes and that a large fraction of the duplicated gene copies becomes non-functional by accumulation of deleterious mutations. In order to describe this phenomenon, we systematically searched the 6404 intergenic regions (IRs) of the genome of Saccharomyces cerevisiae for traces of coding sequences presenting degenerated but still recognizable sequence similarity with active open reading frames (5823 annotated ORFs). We detected a total of 124 anciently coding regions, or "gene relics", showing similarity to a total of 149 distinct active ORFs. This set of relics shows a continuum of sequence degeneration from those whose sequence is slightly altered compared to the functional ORF (classically defined as pseudogenes), to those that contains so many deleterious mutations, as to reach the limit of recognition. Gene relics are more concentrated in the subtelomeric regions of the chromosomes, reflecting the high plasticity of these regions. The presence of relics also revealed ancestral duplication events of chromosomal segments that were previously undetected. Some of these segments are intermingled with the more easily recognizable ancestral blocks of duplication, indicating successive duplication events. We present a compilation of all the data available, leading to a total of 278 pseudogenes in the genome of S. cerevisiae.

Chromosomes, Fungal↗

PubMed2003

A novel design of whole-genome microarray probes for Saccharomyces cerevisiae which minimizes cross-hybridization.

BACKGROUND: Numerous DNA microarray hybridization experiments have been performed in yeast over the last years using either synthetic oligonucleotides or PCR-amplified coding sequences as probes. The design and quality of the microarray probes are of critical importance for hybridization experiments as well as subsequent analysis of the data. RESULTS: We present here a novel design of Saccharomyces cerevisiae microarrays based on a refined annotation of the genome and with the aim of reducing cross-hybridization between related sequences. An effort was made to design probes of similar lengths, preferably located in the 3'-end of reading frames. The sequence of each gene was compared against the entire yeast genome and optimal sub-segments giving no predicted cross-hybridization were selected. A total of 5660 novel probes (more than 97% of the yeast genes) were designed. For the remaining 143 genes, cross-hybridization was unavoidable. Using a set of 18 deletant strains, we have experimentally validated our cross-hybridization procedure. Sensitivity, reproducibility and dynamic range of these new microarrays have been measured. Based on this experience, we have written a novel program to design long oligonucleotides for microarray hybridizations of complete genome sequences. CONCLUSIONS: A validated procedure to predict cross-hybridization in microarray probe design was defined in this work. Subsequently, a novel Saccharomyces cerevisiae microarray (which minimizes cross-hybridization) was designed and constructed. Arrays are available at Eurogentec S. A. Finally, we propose a novel design program, OliD, which allows automatic oligonucleotide design for microarrays. The OliD program is available from authors.

Base Sequence↗

PubMed2003

Anti-inflammatory activity of erycristagallin, a pterocarpene from Erythrina mildbraedii.

Erycristagallin, a pterocarpene isolated from Erythrina mildbraedii, was tested in vitro for its antioxidant properties on the stable 2,2-diphenyl-1-pycryl-hydrazyl (DPPH) free radical and on the arachidonic acid metabolism. In addition, erycristagallin was tested on different experimental models of inflammation, such as the acute and chronic inflammation induced by the application of 12-O-tetradecanoylphorbol 13-acetate (TPA) on mice and the phospholipase A(2)-induced mouse paw oedema test. In the carrageenan-induced mouse paw oedema test, the ethyl acetate extract obtained from E. mildbraedii showed anti-inflammatory activity, and erycristagallin was isolated as the active principle. In vivo, erycristagallin significantly inhibited the phospholipase A(2)-induced mouse paw oedema as well as the mouse ear oedema induced by TPA (ID(50)<10 microg/ear). Moreover, it significantly reduced the chronic inflammation and leukocyte infiltration induced by repeated application of TPA. In vitro, erycristagallin inhibited the arachidonic acid metabolism via the 5-lipoxygenase pathway in rat polymorphonuclear leukocytes (IC(50)=23.4 microM), but had no effect on cyclooxygenase-1 metabolism in human platelets, while showing antioxidant activity in the DPPH test. As with other phenolics, the anti-inflammatory activity of erycristagallin may be based on its capacity to inhibit the arachidonic acid metabolism via the 5-lipoxygenase pathway.

Animals↗

PubMed2003

Warangalone, the isoflavonoid anti-inflammatory principle of Erythrina addisoniae stem bark.

The prenylisoflavone warangalone has been isolated from the bark of Erythrina addisoniae. This compound, previously recognized as a powerful inhibitor of protein kinase A, showed marked effectiveness as an anti-inflammatory on the phospholipase A(2)-induced paw edema and on the 12-O-tetradecanoylphorbol 13-acetate-induced ear edema in mice, after systemic and local administration, respectively.

Animals↗

PubMed2003

Novel transporters from hemiascomycete yeasts.

We screened nearly one thousand random sequenced targets obtained by partial sequencing of 13 hemiascomycete genomes identified by higher amino acid sequence similarity to a non-Saccharomyces cerevisiae protein than to a S. Cerevisiae protein. Among those sequences we have identified 36 novel phylogenetic clusters of putative transporters which, according to the Transport Commission system (TC-DB, 2002; http:// tcdb.ucsd.edu/tcdb), do not belong to acknowledged S. Cerevisiae protein families [De Hertogh et al.: Funct. Integr. Genomics 2002;2:154-170; http://cbi.labri.u-bordeaux.fr/Genolevures]. These novel hemiascomycete transporters comprise 3 channels, 23 secondary transporters, 5 primary transporters and 5 membrane proteins of unknown function.

Ascomycota↗

PubMed2002

Phylogenetic classification of transporters and other membrane proteins from Saccharomyces cerevisiae.

On the basis of functional and phylogenetic criteria, we have identified a total of 229 subfamilies and 111 singletons predicted to carry out transport or other membrane functions in Saccharomyces cerevisiae. We have extended the Transporter Classification (TC) and created a Membrane Classification (MC) for non-transporter membrane proteins. Using the preliminary phylogenetic digits X, Y, Z (for new families, subfamilies, and clusters, respectively), we allocated a five-digit number to 850 proteins predicted to contain more than two transmembrane domains. Compared with a previous TC of the yeast genome, we classified an additional set of 538 membrane proteins (transporters and non-transporters) and identified 111 novel phylogenetic subfamilies.

Membrane Proteins↗

PubMed2002

Identification and functional analysis of the Saccharomyces cerevisiae nicotinamidase gene, PNC1.

Nicotinamidase (NAMase) from the budding yeast, Saccharomyces cerevisiae, was purified by Ni(2+) affinity chromatography and gel filtration. N-terminal microsequencing revealed sequence identity with a hypothetical polypeptide encoded by the yeast YGL037C open reading frame sharing 30% sequence identity with Escherichia coli pyrazinamidase/nicotinamidase. A yeast strain in which the NAMase gene, hereafter named PNC1, was deleted shows a decreased intracellular NAD(+) concentration, consistent with the loss of NAMase activity in the null mutant. In wild-type strains, NAMase activity is stimulated during the stationary phase of growth, by various hyperosmotic shocks or by ethanol treatment. Using a P(PNC1)::lacZ gene fusion, we have shown that this stimulation of NAMase activity results from increased levels of the protein and requires stress response elements in the 5'non-coding region of PNC1. These results suggest that NAMase helps yeast cells to adapt to various stress conditions and nutrient depletion, most likely via the activation of NAD-dependent biological processes.

Amidohydrolases↗