Publications by authors named "Frédéric Collin"

9 Publications

  • Page 1 of 1

The importance of the body-specificity in the evaluation of visuospatial working memory.

Neuropsychol Dev Cogn B Aging Neuropsychol Cogn 2021 Jul 7;28(4):559-569. Epub 2020 Aug 7.

Laboratoire Epsylon (EA 4556); Université Paul Valéry , Montpellier, France.

This work is rooted in the embodied cognition paradigm applied to the evaluation of visuospatial memory span. We aimed to test whether manuospatial incompatibility affects the evaluation of visuospatial working memory. Older and younger participants were tested under two different spatial field conditions, namely manuospatial incompatibility and manuospatial compatibility, using the standard Corsi Block Tapping Task. The results show that a manuospatial compatibility condition helped both younger and older participants to increase their visuospatial working memory span compared to the traditional manuospatial incompatibility condition. By analyzing the data, our results showed an increase of visuospatial memory span in manuospatial compatibility condition (i.e., the experimenter using his left hand and the participant his right hand) compared to manuospatial incompatibility condition for younger and older adults. We recommend that the interaction between body and cognition would be taken into account in clinical evaluation methods.
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http://dx.doi.org/10.1080/13825585.2020.1799925DOI Listing
July 2021

A β-hairpin is a Minimal Latch that Supports Positive Supercoiling by Reverse Gyrase.

J Mol Biol 2020 07 24;432(16):4762-4771. Epub 2020 Jun 24.

Institute for Physical Chemistry, University of Muenster, Corrensstrasse 30, D-48149 Muenster, Germany. Electronic address:

Reverse gyrase is a unique type I topoisomerase that catalyzes the introduction of positive supercoils into DNA in an ATP-dependent reaction. Supercoiling is the result of a functional cooperation of the N-terminal helicase domain with the C-terminal topoisomerase domain. The helicase domain is a nucleotide-dependent conformational switch that alternates between open and closed states with different affinities for single- and double-stranded DNA. The isolated helicase domain as well as full-length reverse gyrase can transiently unwind double-stranded regions in an ATP-dependent reaction. The latch region of reverse gyrase, an insertion into the helicase domain with little conservation in sequence and length, has been proposed to coordinate events in the helicase domain with strand passage by the topoisomerase domain. Latch deletions lead to a reduction in or complete loss of supercoiling activity. Here we show that the latch consists of two functional parts, a globular domain that is dispensable for DNA supercoiling and a β-hairpin that connects the globular domain to the helicase domain and is required for supercoiling activity. The β-hairpin thus constitutes a minimal latch that couples ATP-dependent processes in the helicase domain to DNA processing by the topoisomerase domain.
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http://dx.doi.org/10.1016/j.jmb.2020.06.018DOI Listing
July 2020

The Microbial Toxin Microcin B17: Prospects for the Development of New Antibacterial Agents.

J Mol Biol 2019 08 8;431(18):3400-3426. Epub 2019 Jun 8.

Department Biological Chemistry, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK. Electronic address:

Microcin B17 (MccB17) is an antibacterial peptide produced by strains of Escherichia coli harboring the plasmid-borne mccB17 operon. MccB17 possesses many notable features. It is able to stabilize the transient DNA gyrase-DNA cleavage complex, a very efficient mode of action shared with the highly successful fluoroquinolone drugs. MccB17 stabilizes this complex by a distinct mechanism making it potentially valuable in the fight against bacterial antibiotic resistance. MccB17 was the first compound discovered from the thiazole/oxazole-modified microcins family and the linear azole-containing peptides; these ribosomal peptides are post-translationally modified to convert serine and cysteine residues into oxazole and thiazole rings. These chemical moieties are found in many other bioactive compounds like the vitamin thiamine, the anti-cancer drug bleomycin, the antibacterial sulfathiazole and the antiviral nitazoxanide. Therefore, the biosynthetic machinery that produces these azole rings is noteworthy as a general method to create bioactive compounds. Our knowledge of MccB17 now extends to many aspects of antibacterial-bacteria interactions: production, transport, interaction with its target, and resistance mechanisms; this knowledge has wide potential applicability. After a long time with limited progress on MccB17, recent publications have addressed critical aspects of MccB17 biosynthesis as well as an explosion in the discovery of new related compounds in the thiazole/oxazole-modified microcins/linear azole-containing peptides family. It is therefore timely to summarize the evidence gathered over more than 40 years about this still enigmatic molecule and place it in the wider context of antibacterials.
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http://dx.doi.org/10.1016/j.jmb.2019.05.050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6722960PMC
August 2019

Dietary and Microbial Oxazoles Induce Intestinal Inflammation by Modulating Aryl Hydrocarbon Receptor Responses.

Cell 2018 05;173(5):1123-1134.e11

Division of Gastroenterology, Hepatology, and Endoscopy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address:

Genome-wide association studies have identified risk loci associated with the development of inflammatory bowel disease, while epidemiological studies have emphasized that pathogenesis likely involves host interactions with environmental elements whose source and structure need to be defined. Here, we identify a class of compounds derived from dietary, microbial, and industrial sources that are characterized by the presence of a five-membered oxazole ring and induce CD1d-dependent intestinal inflammation. We observe that minimal oxazole structures modulate natural killer T cell-dependent inflammation by regulating lipid antigen presentation by CD1d on intestinal epithelial cells (IECs). CD1d-restricted production of interleukin 10 by IECs is limited through activity of the aryl hydrocarbon receptor (AhR) pathway in response to oxazole induction of tryptophan metabolites. As such, the depletion of the AhR in the intestinal epithelium abrogates oxazole-induced inflammation. In summary, we identify environmentally derived oxazoles as triggers of CD1d-dependent intestinal inflammatory responses that occur via activation of the AhR in the intestinal epithelium.
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http://dx.doi.org/10.1016/j.cell.2018.04.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6119676PMC
May 2018

Lead selection and characterization of antitubercular compounds using the Nested Chemical Library.

Tuberculosis (Edinb) 2015 Jun 28;95 Suppl 1:S200-6. Epub 2015 Feb 28.

MTA-SE Pathobiochemistry Research Group, Department of Medical Chemistry, Semmelweis University, Tűzoltó u. 37-47, H-1094 Budapest, Hungary; Vichem Chemie Research Ltd., Herman Ottó u. 15, H-1022 Budapest, Hungary. Electronic address:

Discovering new drugs to treat tuberculosis more efficiently and to overcome multidrug resistance is a world health priority. To find novel antitubercular agents several approaches have been used in various institutions worldwide, including target-based approaches against several validated mycobacterial enzymes and phenotypic screens. We screened more than 17,000 compounds from Vichem's Nested Chemical Library™ using an integrated strategy involving whole cell-based assays with Corynebacterium glutamicum and Mycobacterium tuberculosis, and target-based assays with protein kinases PknA, PknB and PknG as well as other targets such as PimA and bacterial topoisomerases simultaneously. With the help of the target-based approach we have found very potent hits inhibiting the selected target enzymes, but good minimal inhibitory concentrations (MIC) against M. tuberculosis were not achieved. Focussing on the whole cell-based approach several potent hits were found which displayed minimal inhibitory concentrations (MIC) against M. tuberculosis below 10 μM and were non-mutagenic, non-cytotoxic and the targets of some of the hits were also identified. The most active hits represented various scaffolds. Medicinal chemistry-based lead optimization was performed applying various strategies and, as a consequence, a series of novel potent compounds were synthesized. These efforts resulted in some effective potential antitubercular lead compounds which were confirmed in phenotypic assays.
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http://dx.doi.org/10.1016/j.tube.2015.02.028DOI Listing
June 2015

Synthesis of full length and truncated microcin B17 analogues as DNA gyrase poisons.

Org Biomol Chem 2014 Mar;12(10):1570-8

School of Chemistry, The University of Sydney, NSW 2006, Australia.

Microcin B17 (MccB17) is a post-translationally modified peptide containing thiazole and oxazole heterocycles that interrupt the peptide backbone. MccB17 is capable of poisoning DNA gyrase through stabilization of the gyrase-DNA cleavage complex and has therefore attracted significant attention. Using a combination of Fmoc-strategy solid-phase peptide synthesis and solution-phase fragment assembly we have prepared a library of full-length and truncated MccB17 analogues to investigate key structural requirements for gyrase-poisoning activity. Synthetic peptides lacking the glycine-rich N-terminal portion of the full-length sequence showed strong stabilization of the gyrase-DNA cleavage complex with increased potency relative to the full-length sequences. This truncation, however, led to a decrease in antibacterial activity of these analogues relative to their full-length counterparts indicating a potential role of the N-terminal region of the natural product for cellular uptake.
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http://dx.doi.org/10.1039/c3ob42516aDOI Listing
March 2014

Fragments of the bacterial toxin microcin B17 as gyrase poisons.

PLoS One 2013 10;8(4):e61459. Epub 2013 Apr 10.

Department of Biological Chemistry, John Innes Centre, Norwich Research Park, Norwich, United Kingdom.

Fluoroquinolones are very important drugs in the clinical antibacterial arsenal; their success is principally due to their mode of action: the stabilisation of a gyrase-DNA intermediate (the cleavage complex), which triggers a chain of events leading to cell death. Microcin B17 (MccB17) is a modified peptide bacterial toxin that acts by a similar mode of action, but is unfortunately unsuitable as a therapeutic drug. However, its structure and mechanism could inspire the design of new antibacterial compounds that are needed to circumvent the rise in bacterial resistance to current antibiotics. Here we describe the investigation of the structural features responsible for MccB17 activity and the identification of fragments of the toxin that retain the ability to stabilise the cleavage complex.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0061459PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3622597PMC
October 2013

The naphthoquinone diospyrin is an inhibitor of DNA gyrase with a novel mechanism of action.

J Biol Chem 2013 Feb 28;288(7):5149-56. Epub 2012 Dec 28.

Department of Biological Chemistry, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, United Kingdom.

Tuberculosis and other bacterial diseases represent a significant threat to human health. The DNA topoisomerases are excellent targets for chemotherapy, and DNA gyrase in particular is a well-validated target for antibacterial agents. Naphthoquinones (e.g. diospyrin and 7-methyljuglone) have been shown to have therapeutic potential, particularly against Mycobacterium tuberculosis. We have found that these compounds are inhibitors of the supercoiling reaction catalyzed by M. tuberculosis gyrase and other gyrases. Our evidence strongly suggests that the compounds bind to the N-terminal domain of GyrB, which contains the ATPase active site, but are not competitive inhibitors of the ATPase reaction. We propose that naphthoquinones bind to GyrB at a novel site close to the ATPase site. This novel mode of action could be exploited to develop new antibacterial agents.
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http://dx.doi.org/10.1074/jbc.M112.419069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3576119PMC
February 2013

Exploiting bacterial DNA gyrase as a drug target: current state and perspectives.

Appl Microbiol Biotechnol 2011 Nov 9;92(3):479-97. Epub 2011 Sep 9.

Department Biological Chemistry, John Innes Centre, Norwich Research Park, Norwich, NR4 7UH, UK.

DNA gyrase is a type II topoisomerase that can introduce negative supercoils into DNA at the expense of ATP hydrolysis. It is essential in all bacteria but absent from higher eukaryotes, making it an attractive target for antibacterials. The fluoroquinolones are examples of very successful gyrase-targeted drugs, but the rise in bacterial resistance to these agents means that we not only need to seek new compounds, but also new modes of inhibition of this enzyme. We review known gyrase-specific drugs and toxins and assess the prospects for developing new antibacterials targeted to this enzyme.
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http://dx.doi.org/10.1007/s00253-011-3557-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3189412PMC
November 2011