Dominique Clermont

Bio: Dominique Clermont is an academic researcher from Pasteur Institute. The author has contributed to research in topics: Biology & 16S ribosomal RNA. The author has an hindex of 20, co-authored 65 publications receiving 3127 citations.

The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide

Abstract: Cyclophosphamide is one of several clinically important cancer drugs whose therapeutic efficacy is due in part to their ability to stimulate antitumor immune responses. Studying mouse models, we demonstrate that cyclophosphamide alters the composition of microbiota in the small intestine and induces the translocation of selected species of Gram-positive bacteria into secondary lymphoid organs. There, these bacteria stimulate the generation of a specific subset of "pathogenic" T helper 17 (pT(H)17) cells and memory T(H)1 immune responses. Tumor-bearing mice that were germ-free or that had been treated with antibiotics to kill Gram-positive bacteria showed a reduction in pT(H)17 responses, and their tumors were resistant to cyclophosphamide. Adoptive transfer of pT(H)17 cells partially restored the antitumor efficacy of cyclophosphamide. These results suggest that the gut microbiota help shape the anticancer immune response.

Correction: Corrigendum: Streptococcus agalactiae clones infecting humans were selected and fixed through the extensive use of tetracycline

Abstract: Nature Communications 5: Article number:4544 (2014); Published 4 Aug 2014; Updated 28 Jan 2015 The original version of this Article contained an error in the spelling of a member of the DEVANI Consortium, Lucilla Baldassarri, which was incorrectly given as Lucilia Baldassari. This has now been corrected in both the PDF and HTML versions of the Article.

The Genomic Diversification of the Whole Acinetobacter Genus: Origins, Mechanisms, and Consequences

Abstract: Bacterial genomics has greatly expanded our understanding of microdiversification patterns within a species, but analyses at higher taxonomical levels are necessary to understand and predict the independent rise of pathogens in a genus We have sampled, sequenced, and assessed the diversity of genomes of validly named and tentative species of the Acinetobacter genus, a clade including major nosocomial pathogens and biotechnologically important species We inferred a robust global phylogeny and delimited several new putative species The genus is very ancient and extremely diverse: Genomes of highly divergent species share more orthologs than certain strains within a species We systematically characterized elements and mechanisms driving genome diversification, such as conjugative elements, insertion sequences, and natural transformation We found many error-prone polymerases that may play a role in resistance to toxins, antibiotics, and in the generation of genetic variation Surprisingly, temperate phages, poorly studied in Acinetobacter, were found to account for a significant fraction of most genomes Accordingly, many genomes encode clustered regularly interspaced short palindromic repeats (CRISPR)-Cas systems with some of the largest CRISPR-arrays found so far in bacteria Integrons are strongly overrepresented in Acinetobacter baumannii, which correlates with its frequent resistance to antibiotics Our data suggest that A baumannii arose from an ancient population bottleneck followed by population expansion under strong purifying selection The outstanding diversification of the species occurred largely by horizontal transfer, including some allelic recombination, at specific hotspots preferentially located close to the replication terminus Our work sets a quantitative basis to understand the diversification of Acinetobacter into emerging resistant and versatile pathogens

Listeria rocourtiae sp. nov.

Abstract: A Listeria-like strain isolated in Austria from pre-cut lettuce fitted the description of the genus Listeria although it could not be assigned to any of the known species. Comparison of the rrs gene (encoding 16S rRNA) sequence and gene content by DNA-array indicated affiliation to the genus Listeria. Phylogenetic distance from known species of the genus Listeria indicated that it represents a novel species. Since it can be differentiated from all other known species of the genus Listeria by using phenotypic tests, the name Listeria rocourtiae sp. nov. is proposed for the novel species. The type strain is CIP 109804T (=DSM 22097T =Allerberger 700284/02T). The type strain is avirulent as assessed by cell culture assays and inoculation of mice.

Streptococcus agalactiae clones infecting humans were selected and fixed through the extensive use of tetracycline

Abstract: Streptococcus agalactiae (Group B Streptococcus, GBS) is a commensal of the digestive and genitourinary tracts of humans that emerged as the leading cause of bacterial neonatal infections in Europe and North America during the 1960s. Due to the lack of epidemiological and genomic data, the reasons for this emergence are unknown. Here we show by comparative genome analysis and phylogenetic reconstruction of 229 isolates that the rise of human GBS infections corresponds to the selection and worldwide dissemination of only a few clones. The parallel expansion of the clones is preceded by the insertion of integrative and conjugative elements conferring tetracycline resistance (TcR). Thus, we propose that the use of tetracycline from 1948 onwards led in humans to the complete replacement of a diverse GBS population by only few TcR clones particularly well adapted to their host, causing the observed emergence of GBS diseases in neonates.

SPAdes, a new genome assembly algorithm and its applications to single-cell sequencing ( 7th Annual SFAF Meeting, 2012)

Abstract: The lion's share of bacteria in various environments cannot be cloned in the laboratory and thus cannot be sequenced using existing technologies. A major goal of single-cell genomics is to complement gene-centric metagenomic data with whole-genome assemblies of uncultivated organisms. Assembly of single-cell data is challenging because of highly non-uniform read coverage as well as elevated levels of sequencing errors and chimeric reads. We describe SPAdes, a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V-SC assembler (specialized for single-cell data) and on popular assemblers Velvet and SoapDeNovo (for multicell data). SPAdes generates single-cell assemblies, providing information about genomes of uncultivatable bacteria that vastly exceeds what may be obtained via traditional metagenomics studies. SPAdes is available online ( http://bioinf.spbau.ru/spades ). It is distributed as open source software.

Tetracycline Antibiotics: Mode of Action, Applications, Molecular Biology, and Epidemiology of Bacterial Resistance

Abstract: Tetracyclines were discovered in the 1940s and exhibited activity against a wide range of microorganisms including gram-positive and gram-negative bacteria, chlamydiae, mycoplasmas, rickettsiae, and protozoan parasites. They are inexpensive antibiotics, which have been used extensively in the prophlylaxis and therapy of human and animal infections and also at subtherapeutic levels in animal feed as growth promoters. The first tetracycline-resistant bacterium, Shigella dysenteriae, was isolated in 1953. Tetracycline resistance now occurs in an increasing number of pathogenic, opportunistic, and commensal bacteria. The presence of tetracycline-resistant pathogens limits the use of these agents in treatment of disease. Tetracycline resistance is often due to the acquisition of new genes, which code for energy-dependent efflux of tetracyclines or for a protein that protects bacterial ribosomes from the action of tetracyclines. Many of these genes are associated with mobile plasmids or transposons and can be distinguished from each other using molecular methods including DNA-DNA hybridization with oligonucleotide probes and DNA sequencing. A limited number of bacteria acquire resistance by mutations, which alter the permeability of the outer membrane porins and/or lipopolysaccharides in the outer membrane, change the regulation of innate efflux systems, or alter the 16S rRNA. New tetracycline derivatives are being examined, although their role in treatment is not clear. Changing the use of tetracyclines in human and animal health as well as in food production is needed if we are to continue to use this class of broad-spectrum antimicrobials through the present century.

Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors

Abstract: Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis induce sustained clinical responses in a sizable minority of cancer patients. We found that primary resistance to ICIs can be attributed to abnormal gut microbiome composition. Antibiotics inhibited the clinical benefit of ICIs in patients with advanced cancer. Fecal microbiota transplantation (FMT) from cancer patients who responded to ICIs into germ-free or antibiotic-treated mice ameliorated the antitumor effects of PD-1 blockade, whereas FMT from nonresponding patients failed to do so. Metagenomics of patient stool samples at diagnosis revealed correlations between clinical responses to ICIs and the relative abundance of Akkermansia muciniphila Oral supplementation with A. muciniphila after FMT with nonresponder feces restored the efficacy of PD-1 blockade in an interleukin-12-dependent manner by increasing the recruitment of CCR9+CXCR3+CD4+ T lymphocytes into mouse tumor beds.