Publications
2014
Schwarzmüller Tobias, Ma Biao, Hiller Ekkehard, Istel Fabian, Tscherner Michael, Brunke Sascha, Ames Lauren, Firon Arnaud, Green Brian, Cabral Vitor, Marcet-Houben Marina, Jacobsen Ilse D, Quintin Jessica, Seider Katja, Frohner Ingrid, Glaser Walter, Jungwirth Helmut, Bachellier-Bassi Sophie, Chauvel Murielle, Zeidler Ute, Ferrandon Dominique, Gabaldón Toni, Hube Bernhard, d'Enfert Christophe, Rupp Steffen, Cormack Brendan, Haynes Ken, Kuchler Karl
Systematic phenotyping of a large-scale Candida glabrata deletion collection reveals novel antifungal tolerance genes Journal Article
In: PLoS Pathog., vol. 10, no. 6, pp. e1004211, 2014, ISSN: 1553-7374.
Abstract | Links | BibTeX | Tags: Antifungal Agents, Azoles, Biofilms, Candida glabrata, Candidiasis, Cell Wall, Drug Resistance, Echinocandins, ferrandon, Fungal, Fungal Proteins, Gene Deletion, Gene Knockout Techniques, Gene Library, M3i, Microbial Sensitivity Tests, Osmotic Pressure, Phenotype
@article{schwarzmuller_systematic_2014b,
title = {Systematic phenotyping of a large-scale Candida glabrata deletion collection reveals novel antifungal tolerance genes},
author = {Tobias Schwarzmüller and Biao Ma and Ekkehard Hiller and Fabian Istel and Michael Tscherner and Sascha Brunke and Lauren Ames and Arnaud Firon and Brian Green and Vitor Cabral and Marina Marcet-Houben and Ilse D Jacobsen and Jessica Quintin and Katja Seider and Ingrid Frohner and Walter Glaser and Helmut Jungwirth and Sophie Bachellier-Bassi and Murielle Chauvel and Ute Zeidler and Dominique Ferrandon and Toni Gabaldón and Bernhard Hube and Christophe d'Enfert and Steffen Rupp and Brendan Cormack and Ken Haynes and Karl Kuchler},
doi = {10.1371/journal.ppat.1004211},
issn = {1553-7374},
year = {2014},
date = {2014-01-01},
journal = {PLoS Pathog.},
volume = {10},
number = {6},
pages = {e1004211},
abstract = {The opportunistic fungal pathogen Candida glabrata is a frequent cause of candidiasis, causing infections ranging from superficial to life-threatening disseminated disease. The inherent tolerance of C. glabrata to azole drugs makes this pathogen a serious clinical threat. To identify novel genes implicated in antifungal drug tolerance, we have constructed a large-scale C. glabrata deletion library consisting of 619 unique, individually bar-coded mutant strains, each lacking one specific gene, all together representing almost 12% of the genome. Functional analysis of this library in a series of phenotypic and fitness assays identified numerous genes required for growth of C. glabrata under normal or specific stress conditions, as well as a number of novel genes involved in tolerance to clinically important antifungal drugs such as azoles and echinocandins. We identified 38 deletion strains displaying strongly increased susceptibility to caspofungin, 28 of which encoding proteins that have not previously been linked to echinocandin tolerance. Our results demonstrate the potential of the C. glabrata mutant collection as a valuable resource in functional genomics studies of this important fungal pathogen of humans, and to facilitate the identification of putative novel antifungal drug target and virulence genes.},
keywords = {Antifungal Agents, Azoles, Biofilms, Candida glabrata, Candidiasis, Cell Wall, Drug Resistance, Echinocandins, ferrandon, Fungal, Fungal Proteins, Gene Deletion, Gene Knockout Techniques, Gene Library, M3i, Microbial Sensitivity Tests, Osmotic Pressure, Phenotype},
pubstate = {published},
tppubtype = {article}
}
Hemmerlin Andréa, Tritsch Denis, Hammann Philippe, Rohmer Michel, Bach Thomas J
Profiling of defense responses in Escherichia coli treated with fosmidomycin. Journal Article
In: Biochimie, vol. 99, pp. 54–62, 2014, ISSN: 1638-6183 0300-9084, (Place: France).
Abstract | Links | BibTeX | Tags: 1-Deoxy-d-xylulose 5-phosphate reducto-isomerase, Anti-Bacterial Agents/*pharmacology, Antibiotics, Bacterial, Disk Diffusion Antimicrobial Tests, Drug Resistance, Escherichia coli Proteins/*metabolism, Escherichia coli/drug effects/growth & development/*metabolism, Fosfomycin/*analogs & derivatives/pharmacology, Fosmidomycin, Isoprenoid, Oxidative Stress, Phenotype, PPSE, Proteome/metabolism, Resistance acquisition
@article{hemmerlin_profiling_2014,
title = {Profiling of defense responses in Escherichia coli treated with fosmidomycin.},
author = {Andréa Hemmerlin and Denis Tritsch and Philippe Hammann and Michel Rohmer and Thomas J Bach},
doi = {10.1016/j.biochi.2013.11.008},
issn = {1638-6183 0300-9084},
year = {2014},
date = {2014-01-01},
journal = {Biochimie},
volume = {99},
pages = {54--62},
abstract = {The mevalonate-independent isoprenoid biosynthesis pathway has been recognized as a promising target for designing new antibiotics. But pathogens treated with compounds such as fosmidomycin, a slow binding inhibitor of 1-deoxy-D-xylulose 5-phosphate reducto-isomerase, the second enzyme in this pathway, develop rapid drug resistance. In Escherichia coli, acquired resistance results mostly from inactivating the cAMP-dependent glpT transporter, thereby preventing import of the inhibitor. Such mutant strains are characterized by cross-resistance to fosfomycin, by susceptibility to efflux pump inhibitors, by disability to use glycerol 3-phosphate as a carbon source or by increased activity of the promoter controlling the expression of the glpABC regulon when grown in presence of fosmidomycin. The quite challenging task consists in conceiving new and efficient inhibitors avoiding resistance acquisition. They should be efficient in blocking the target enzyme, but should also be durably taken up by the organism. To address this issue, it is essential to characterize the mechanisms the pathogen exploits to defeat the antibiotic before resistance is acquired. Having this in mind, a 2-D Fluorescence Difference Gel Electrophoresis proteomic approach has been applied to identify defense responses in E. coli cells being shortly exposed to fosmidomycin (3 h). It seems that combined strategies are promptly induced. The major one consists in preventing toxic effects of the compound either by adapting metabolism and/or by getting rid of the molecule. The strategy adopted by the bacteria is to eliminate the drug from the cell or to increase the tolerance to oxidative stress. The design of new, but still efficient drugs, needs consideration of such rapid modulations required to adapt cell growth in contact of the inhibitor.},
note = {Place: France},
keywords = {1-Deoxy-d-xylulose 5-phosphate reducto-isomerase, Anti-Bacterial Agents/*pharmacology, Antibiotics, Bacterial, Disk Diffusion Antimicrobial Tests, Drug Resistance, Escherichia coli Proteins/*metabolism, Escherichia coli/drug effects/growth & development/*metabolism, Fosfomycin/*analogs & derivatives/pharmacology, Fosmidomycin, Isoprenoid, Oxidative Stress, Phenotype, PPSE, Proteome/metabolism, Resistance acquisition},
pubstate = {published},
tppubtype = {article}
}
2011
Limmer Stefanie, Quintin Jessica, Hetru Charles, Ferrandon Dominique
Virulence on the fly: Drosophila melanogaster as a model genetic organism to decipher host-pathogen interactions Journal Article
In: Curr Drug Targets, vol. 12, no. 7, pp. 978–999, 2011, ISSN: 1873-5592.
Abstract | BibTeX | Tags: Animal, Animals, Anti-Infective Agents, Disease Models, Drug Delivery Systems, Drug Design, Drug Resistance, ferrandon, Fungi, High-Throughput Screening Assays, Host-Pathogen Interactions, Humans, M3i, Microbial, Pseudomonas aeruginosa
@article{limmer_virulence_2011b,
title = {Virulence on the fly: Drosophila melanogaster as a model genetic organism to decipher host-pathogen interactions},
author = {Stefanie Limmer and Jessica Quintin and Charles Hetru and Dominique Ferrandon},
issn = {1873-5592},
year = {2011},
date = {2011-06-01},
journal = {Curr Drug Targets},
volume = {12},
number = {7},
pages = {978--999},
abstract = {To gain an in-depth grasp of infectious processes one has to know the specific interactions between the virulence factors of the pathogen and the host defense mechanisms. A thorough understanding is crucial for identifying potential new drug targets and designing drugs against which the pathogens might not develop resistance easily. Model organisms are a useful tool for this endeavor, thanks to the power of their genetics. Drosophila melanogaster is widely used to study host-pathogen interactions. Its basal immune response is well understood and is briefly reviewed here. Considerations relevant to choosing an adequate infection model are discussed. This review then focuses mainly on infections with two categories of pathogens, the well-studied Gram-negative bacterium Pseudomonas aeruginosa and infections by fungi of medical interest. These examples provide an overview over the current knowledge on Drosophila-pathogen interactions and illustrate the approaches that can be used to study those interactions. We also discuss the usefulness and limits of Drosophila infection models for studying specific host-pathogen interactions and high-throughput drug screening.},
keywords = {Animal, Animals, Anti-Infective Agents, Disease Models, Drug Delivery Systems, Drug Design, Drug Resistance, ferrandon, Fungi, High-Throughput Screening Assays, Host-Pathogen Interactions, Humans, M3i, Microbial, Pseudomonas aeruginosa},
pubstate = {published},
tppubtype = {article}
}
Benincasa Monica, Pacor Sabrina, Wu Wei, Prato Maurizio, Bianco Alberto, Gennaro Renato
Antifungal activity of amphotericin B conjugated to carbon nanotubes Journal Article
In: ACS nano, vol. 5, no. 1, pp. 199–208, 2011, ISSN: 1936-086X.
Abstract | Links | BibTeX | Tags: Amphotericin B, Antifungal Agents, Candida, carbon, Cell Membrane, Deoxycholic Acid, Drug Design, Drug Resistance, Fungal, Humans, I2CT, Jurkat Cells, Kinetics, Membrane Potentials, Nanotubes, Team-Bianco
@article{benincasa_antifungal_2011,
title = {Antifungal activity of amphotericin B conjugated to carbon nanotubes},
author = {Monica Benincasa and Sabrina Pacor and Wei Wu and Maurizio Prato and Alberto Bianco and Renato Gennaro},
doi = {10.1021/nn1023522},
issn = {1936-086X},
year = {2011},
date = {2011-01-01},
journal = {ACS nano},
volume = {5},
number = {1},
pages = {199--208},
abstract = {Amphotericin B (AMB) has long been considered the most effective drug in the treatment of serious invasive fungal infections. There are, however, major limitations to its use, due to several adverse effects, including acute infusional reactions and, most relevant, a dose-dependent nephrotoxicity. At least some of these effects are attributed to the aggregation of AMB as a result of its poor water solubility. To overcome this problem, reformulated versions of the drug have been developed, including a micellar dispersion of AMB with sodium deoxycholate (AMBD), its encapsulation into liposomes, or its incorporation into lipidic complexes. The development of nanobiotechnologies provides novel potential drug delivery systems that make use of nanomaterials such as functionalized carbon nanotubes (f-CNTs), which are emerging as an innovative and efficient tool for the transport and cellular translocation of therapeutic molecules. In this study, we prepared two conjugates between f-CNTs and AMB. The antifungal activity of these conjugates was tested against a collection of reference and clinical fungal strains, in comparison to that of AMB alone or AMBD. Measured minimum inhibition concentration (MIC) values for f-CNT-AMB conjugates were either comparable to or better than those displayed by AMB and AMBD. Furthermore, AMBD-resistant Candida strains were found to be susceptible to f-CNT-AMB 1. Additional studies, aimed at understanding the mechanism of action of the conjugates, suggest a nonlytic mechanism, since the compounds show a major permeabilizing effect on the tested fungal strains only after extended incubation. Interestingly, the f-CNT-AMB 1 does not show any significant toxic effect on Jurkat cells at antifungal concentrations.},
keywords = {Amphotericin B, Antifungal Agents, Candida, carbon, Cell Membrane, Deoxycholic Acid, Drug Design, Drug Resistance, Fungal, Humans, I2CT, Jurkat Cells, Kinetics, Membrane Potentials, Nanotubes, Team-Bianco},
pubstate = {published},
tppubtype = {article}
}
2007
Beutler Bruce, Eidenschenk Celine, Crozat Karine, Imler Jean-Luc, Takeuchi Osamu, Hoffmann Jules A, Akira Shizuo
Genetic analysis of resistance to viral infection Journal Article
In: Nature Reviews. Immunology, vol. 7, no. 10, pp. 753–766, 2007, ISSN: 1474-1741.
Abstract | Links | BibTeX | Tags: Animals, Antiviral Agents, Disease Susceptibility, Drug Resistance, Eukaryotic Cells, hoffmann, Humans, imler, Immunity, M3i, Mutation, Viral, Virus Diseases, viruses
@article{beutler_genetic_2007,
title = {Genetic analysis of resistance to viral infection},
author = {Bruce Beutler and Celine Eidenschenk and Karine Crozat and Jean-Luc Imler and Osamu Takeuchi and Jules A Hoffmann and Shizuo Akira},
doi = {10.1038/nri2174},
issn = {1474-1741},
year = {2007},
date = {2007-10-01},
journal = {Nature Reviews. Immunology},
volume = {7},
number = {10},
pages = {753--766},
abstract = {As machines that reprogramme eukaryotic cells to suit their own purposes, viruses present a difficult problem for multicellular hosts, and indeed, have become one of the central pre-occupations of the immune system. Unable to permanently outpace individual viruses in an evolutionary footrace, higher eukaryotes have evolved broadly active mechanisms with which to sense viruses and suppress their proliferation. These mechanisms have recently been elucidated by a combination of forward and reverse genetic methods. Some of these mechanisms are clearly ancient, whereas others are relatively new. All are remarkably adept at discriminating self from non-self, and allow the host to cope with what might seem an impossible predicament.},
keywords = {Animals, Antiviral Agents, Disease Susceptibility, Drug Resistance, Eukaryotic Cells, hoffmann, Humans, imler, Immunity, M3i, Mutation, Viral, Virus Diseases, viruses},
pubstate = {published},
tppubtype = {article}
}
2006
Vivet-Boudou V, Didierjean J, Isel C, Marquet R
Nucleoside and nucleotide inhibitors of HIV-1 replication Journal Article
In: Cell Mol Life Sci, vol. 63, no. 2, pp. 163-186, 2006, ISBN: 16389458, (1420-682X (Print) Journal Article Review).
Abstract | Links | BibTeX | Tags: Biological Mutation Nucleosides/chemistry/pharmacology Nucleotides/chemistry/pharmacology Protein Structure, Drug Resistance, MARQUET, PAILLART, Tertiary Reverse Transcriptase Inhibitors/*chemistry/*pharmacology Virus Replication, Unité ARN, Viral/*genetics HIV Infections/drug therapy HIV-1/drug effects/*enzymology/genetics Humans Models
@article{,
title = {Nucleoside and nucleotide inhibitors of HIV-1 replication},
author = {V Vivet-Boudou and J Didierjean and C Isel and R Marquet},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16389458},
isbn = {16389458},
year = {2006},
date = {2006-01-01},
journal = {Cell Mol Life Sci},
volume = {63},
number = {2},
pages = {163-186},
abstract = {HIV-1 reverse transcriptase (RT) is one of the main targets for antiviral therapy. Two classes of RT inhibitors can be distinguished: those that are nucleoside or nucleotide analogues (sharing the common NRTIs abbreviation) and those that are not. This review focuses on the NRTIs, which are highly efficient in slowing down viral replication and are used in combination regimens. Unfortunately, the current inhibitors do not completely suppress viral replication and due to the high capacity of adaptation of HIV, allow the selection of drug-resistant viruses. Resistance mechanisms to NRTIs have been extensively investigated and can be divided into two types: improved discrimination of a nucleotide analogue relative to the natural substrate or increased phosphorolytic cleavage of an analogue-blocked primer. This knowledge is important both for the development of new drugs designed to target resistant strains and for the development of new antiviral strategies. The NRTIs currently in clinical trials and new developments in this area are also reviewed.},
note = {1420-682X (Print)
Journal Article
Review},
keywords = {Biological Mutation Nucleosides/chemistry/pharmacology Nucleotides/chemistry/pharmacology Protein Structure, Drug Resistance, MARQUET, PAILLART, Tertiary Reverse Transcriptase Inhibitors/*chemistry/*pharmacology Virus Replication, Unité ARN, Viral/*genetics HIV Infections/drug therapy HIV-1/drug effects/*enzymology/genetics Humans Models},
pubstate = {published},
tppubtype = {article}
}