Cutibacterium acnes (C. acnes) has been implicated in inflammatory acne where highly mutated Christie–Atkins–Munch–Petersen factor (CAMP)1 displays strong toll like receptor (TLR)-2 binding activity. Using specific antibodies, we showed... more
Cutibacterium acnes (C. acnes) has been implicated in inflammatory acne where highly mutated Christie–Atkins–Munch–Petersen factor (CAMP)1 displays strong toll like receptor (TLR)-2 binding activity. Using specific antibodies, we showed that CAMP1 production was independent of C. acnes phylotype and involved in the induction of inflammation. We confirmed that TLR-2 bound both mutated and non-mutated recombinant CAMP1, and peptide array analysis showed that seven peptides (A14, A15, B1, B2, B3, C1 and C3) were involved in TLR-2 binding, located on the same side of the three-dimensional structure of CAMP1. Both mutated and non-mutated recombinant CAMP1 proteins induced the production of C-X-C motif chemokine ligand interleukin (CXCL)8/(IL)-8 in vitro in keratinocytes and that of granulocyte macrophage-colony stimulating factor (GM-CSF), tumor necrosis factor (TNF)-α, IL-1β and IL-10 in ex vivo human skin explants. Only A14, B1 and B2 inhibited the production of CXCL8/IL-8 by keratinoc...
Research Interests:
Acne is a chronic inflammatory multifactorial disease involving the anaerobic bacterium Cutibacterium acnes (C. acnes). Current acne treatments are associated with adverse effects, limiting treatment compliance and use. We showed that... more
Acne is a chronic inflammatory multifactorial disease involving the anaerobic bacterium Cutibacterium acnes (C. acnes). Current acne treatments are associated with adverse effects, limiting treatment compliance and use. We showed that meclozine, an anti-histaminic H1 compound, has anti-inflammatory properties. In Vitro, meclozine reduced the production of CXCL8/IL-8 and IL-1β mRNA and protein by C. acnes-stimulated human keratinocytes and monocytes. No cell toxicity was observed at the IC50. Meclozine prevented the phosphorylation of ERK and JNK. In Vivo, 1% meclozine gel significantly decreased C. acnes-mouse ear induced inflammation by 26.7% (p = 0.021). Ex vivo experiments on human skin explants showed that meclozine decreased the production of GM-CSF, IL-1β and TNF-α at transcriptional and translational levels. In a randomized, double-blind, placebo-controlled proof-of-concept clinical trial on 60 volunteers, 2% meclozine pharmaceutical gel decreased by 20.1% (p < 0.001) the ...
Research Interests:
Human Herpesvirus 8 (HHV-8) is associated with three main severe orphan malignancies, Kaposi’s sarcoma (KS), multicentric Castleman’s disease (MCD), and primary effusion lymphoma (PEL), which present few therapeutic options. We identified... more
Human Herpesvirus 8 (HHV-8) is associated with three main severe orphan malignancies, Kaposi’s sarcoma (KS), multicentric Castleman’s disease (MCD), and primary effusion lymphoma (PEL), which present few therapeutic options. We identified the antimalarial primaquine diphosphate (PQ) as a promising therapeutic candidate for HHV-8-associated PEL and KS. Indeed, PQ strongly reduced cell viability through caspase-dependent apoptosis, specifically in HHV-8-infected PEL cells. Reactive oxygen species (ROS)- and endoplasmic reticulum (ER) stress-mediated apoptosis signaling pathways were found to be part of the in vitro cytotoxic effect of PQ. Moreover, PQ treatment had a clinically positive effect in a nonobese diabetic (NOD)/SCID xenograft PEL mouse model, showing a reduction in tumor growth and an improvement in survival. Finally, an exploratory proof-of-concept clinical trial in four patients harboring severe KS was conducted, with the main objectives to assess the efficacy, the safety...
Research Interests:
We evaluated the utility of the commercial Allplex genital ulcer real-time PCR multiplex assay for detecting Treponema pallidum (TPA), herpes simplex virus 1 (HSV-1) and 2 (HSV-2), and Chlamydia trachomatis serovar L (lymphogranuloma... more
We evaluated the utility of the commercial Allplex genital ulcer real-time PCR multiplex assay for detecting Treponema pallidum (TPA), herpes simplex virus 1 (HSV-1) and 2 (HSV-2), and Chlamydia trachomatis serovar L (lymphogranuloma venereum [LGV]) DNA in mucosal and genital ulcers in the context of suspected syphilis. In total, 374 documented genital and mucosal ulcers from patients with and without syphilis presenting at several sexually transmitted infection (STI) centers in France from October 2010 to December 2016 were analyzed at the National Reference Center (CNR) for Bacterial STIs at Cochin Hospital in Paris. TPA detection results were compared with the final diagnosis based on a combination of clinical examination, serological results, and in-house nested PCR (nPCR).
Research Interests:
Cutibacterium acnes is a member of the skin microbiota found predominantly in regions rich in sebaceous glands. It is involved in maintaining healthy skin and has long been considered a commensal bacterium. Its involvement in various... more
Cutibacterium acnes is a member of the skin microbiota found predominantly in regions rich in sebaceous glands. It is involved in maintaining healthy skin and has long been considered a commensal bacterium. Its involvement in various infections has led to its emergence as an opportunist pathogen. Interactions between C. acnes and the human host, including the human skin microbiota, promote the selection of C. acnes strains capable of producing several virulence factors that increase inflammatory capability. This pathogenic property may be related to many infectious mechanisms, such as an ability to form biofilms and the expression of putative virulence factors capable of triggering host immune responses or enabling C. acnes to adapt to its environment. During the past decade, many studies have identified and characterized several putative virulence factors potentially involved in the pathogenicity of this bacterium. These virulence factors are involved in bacterial attachment to tar...
Research Interests: Microbiology, Biology, Medicine, Virulence, Biofilm, and 4 moreBacteria, Pathogen, Microorganisms, and Virulence factor
Research Interests: Microbiology, Biology, Medicine, Disease susceptibility, Diarrhea, and 15 moreBiological Sciences, Infection and immunity, Escherichia coli, Animals, Bacteria, Mucin, Glycoproteins, Brush Border, Dehydration, Bacterial Adhesion, Escherichia Coli Infections, Fimbria, microvilli, Medical and Health Sciences, and Enterotoxigenic Escherichia coli
Putative receptors of Escherichia coli K88 fimbriae are either tightly membrane bound or an integral part of membranes. Thus, proteins associated with piglet small intestinal mucosae were solubilized by a detergent (deoxycholate). A... more
Putative receptors of Escherichia coli K88 fimbriae are either tightly membrane bound or an integral part of membranes. Thus, proteins associated with piglet small intestinal mucosae were solubilized by a detergent (deoxycholate). A 74-kDa glycoprotein (GP74) purified from enterocyte and brush border membrane preparations was specifically detected in vitro by K88ab fimbriae. GP74 was recognized only in the mucosae of phenotypically adhesive animals. Metaperiodate treatment abolished the recognition, indicating that K88ab fimbriae-GP74 binding required the carbohydrate moiety. This glycoprotein belongs to the transferrin family and differed from the serum transferrin of the same adhesive-phenotype piglets. Unlike intestinal transferrin, serum transferrin was recognized independently of the adhesion phenotype. The glycan moieties of intestinal and serum transferrins differed in their molar compositions. Transferrin GP74 contained one monosialylated and monofucosylated glycan chain of ...
Research Interests: Biology, Medicine, Adhesion, Biological Sciences, Intestinal Mucosa, and 15 moreEscherichia coli, Animals, Bacteria, Glycoproteins, Amino Acids, Digestive System, Swine, Amino Acid Sequence, Bacterial Adhesion, Fimbria, Isoelectric point, Infectivity, Molecular Sequence Data, Medical and Health Sciences, and Enterotoxigenic Escherichia coli
In this study, we identified a receptor for the K88ad fimbrial adhesin of Escherichia coli in neutral glycosphingolipid preparations from intestinal epithelial cells of K88ad-adhesive pigs, which was absent in preparations from... more
In this study, we identified a receptor for the K88ad fimbrial adhesin of Escherichia coli in neutral glycosphingolipid preparations from intestinal epithelial cells of K88ad-adhesive pigs, which was absent in preparations from K88ad-nonadhesive pigs. Neither K88ab nor K88ac adhesin variants bound to this neutral glycosphingolipid. Because this receptor is an intestinal glycosphingolipid that binds K88ad adhesin, it has been designated IGLad. Carbohydrate compositional analysis of a partially purified preparation of IGLad identified galactose, glucose, andN-acetylglucosamine in a ratio of 1.5:1.0:0.5 as the major monosaccharides. Preliminary characterization experiments using lectins showed that IGLad contains the terminal glycanic structure Galβ1-4GlcNAc. Removal of terminal β-linked galactose residues from IGLad decreased the recognition of IGLad by the K88ad adhesin, indicating that terminal β-linked galactose is an essential component of the K88ad adhesin recognition site on IGL...
Research Interests:
We have previously identified two mucin-type sialoglycoproteins from porcine intestinal epithelial cells with approximate molecular masses of 210 (intestinal mucin-type glycoprotein IMTGP-1) and 240 kDa (IMTGP-2) as receptors for the... more
We have previously identified two mucin-type sialoglycoproteins from porcine intestinal epithelial cells with approximate molecular masses of 210 (intestinal mucin-type glycoprotein IMTGP-1) and 240 kDa (IMTGP-2) as receptors for the K88ab and K88ac fimbrial adhesins of Escherichia coli . These receptors are detected in intestinal brush border membrane preparations from pigs with adhesive phenotypes but not from pigs with nonadhesive phenotypes and are postulated to be important determinants of the susceptibility of pigs to K88ab + and K88ac + enterotoxigenic E. coli infections. Using exoglycosidase digestion studies, we have now determined that β-linked galactose is an important component in the recognition of IMTGP-1 and IMTGP-2 by the K88ac adhesin. In addition, we observed a differential distribution of the K88ac adhesin binding activity of IMTGP-1 and IMTGP-2 along the crypt-villus axis, suggesting that receptor activity is dependent on the maturation state of the intestinal ep...
Research Interests:
Research Interests: Genetics, Microbiology, Cancer, Medical Microbiology, Biology, and 15 moreEcology, Infectious Diseases, Medicine, Multidisciplinary, Molecular Epidemiology, Pediatric Infectious Diseases, Biological Sciences, Dna Sequencing, PLoS one, Lineage, Allele, Penicillin, Multilocus sequence typing, DNA sequence, and Medical and Health Sciences
Research Interests:
Treponema pallidum subsp. endemicum (TEN) is the causative agent of endemic syphilis (bejel). An unusual human TEN 11q/j isolate was obtained from a syphilis-like primary genital lesion from a patient that returned to France from... more
Treponema pallidum subsp. endemicum (TEN) is the causative agent of endemic syphilis (bejel). An unusual human TEN 11q/j isolate was obtained from a syphilis-like primary genital lesion from a patient that returned to France from Pakistan. The TEN 11q/j isolate was characterized using nested PCR followed by Sanger sequencing and/or direct Illumina sequencing. Altogether, 44 chromosomal regions were analyzed. Overall, the 11q/j isolate clustered with TEN strains Bosnia A and Iraq B as expected from previous TEN classification of the 11q/j isolate. However, the 11q/j sequence in a 505 bp-long region at the TP0488 locus was similar to Treponema pallidum subsp. pallidum (TPA) strains, but not to TEN Bosnia A and Iraq B sequences, suggesting a recombination event at this locus. Similarly, the 11q/j sequence in a 613 bp-long region at the TP0548 locus was similar to Treponema pallidum subsp. pertenue (TPE) strains, but not to TEN sequences. A detailed analysis of two recombinant loci foun...
Research Interests: Biochemistry, Evolutionary Biology, Genetics, Developmental Biology, Immunology, and 15 moreCancer, Biology, Ecology, Cell Biology, Infectious Diseases, France, Biological Sciences, Humans, Male, Cluster Analysis, Genotype, Adult, Genetic Recombination, Genetic variation, and Medical and Health Sciences
Research Interests:
Recently, the World Health Organization launched a campaign to eradicate the tropical disease yaws, caused by the bacterium Treponema pallidum subsp. pertenue; however, for decades researchers have questioned whether flies act as a vector... more
Recently, the World Health Organization launched a campaign to eradicate the tropical disease yaws, caused by the bacterium Treponema pallidum subsp. pertenue; however, for decades researchers have questioned whether flies act as a vector for the pathogen that could facilitate transmission. A total of 207 fly specimens were trapped in areas of Africa in which T. pallidum-induced skin ulcerations are common in wild baboons; 88 flies from Tarangire National Park and 119 from Lake Manyara National Park in Tanzania were analyzed by PCR for the presence of T. pallidum DNA. We report that in the two study areas, T. pallidum DNA was found in 17-24% of wild-caught flies of the order Diptera. Treponemal DNA sequences obtained from many of the flies match sequences derived from nearby baboon T. pallidum strains, and one of the fly species with an especially high prevalence of T. pallidum DNA, Musca sorbens, has previously been shown to transmit yaws in an experimental setting. Our results rai...
Research Interests:
Gram-positive Streptococcus pyogenes (group A Streptococcus or GAS) is a major skin pathogen and interacts with keratinocytes in cutaneous tissues. GAS can cause diverse suppurative and inflammatory infections, such as cellulitis, a... more
Gram-positive Streptococcus pyogenes (group A Streptococcus or GAS) is a major skin pathogen and interacts with keratinocytes in cutaneous tissues. GAS can cause diverse suppurative and inflammatory infections, such as cellulitis, a common acute bacterial dermo-hypodermitis with a high morbidity. Bacterial isolation yields from the lesions are low despite the strong local inflammation observed, raising numerous questions about the pathogenesis of the infection. Using an in vitro model of GAS-infected keratinocytes, we show that the major ROS produced is the superoxide anion ([Formula: see text]), and that its production is time- and dose-dependent. Using specific modulators of ROS production, we show that [Formula: see text] is mainly synthesized by the cytoplasmic NADPH oxidase. Superoxide anion production leads to keratinocyte necrosis but incomplete inhibition of GAS growth, suggesting that GAS may be partially resistant to the oxidative burst. In conclusion, GAS-stimulated kerat...
Research Interests:
Research Interests: Microbiology, Chemistry, Immunology, Medical Microbiology, Biology, and 15 moreInflammation, Apoptosis, Medicine, Humans, Keratinocytes, Gram Positive, Nitric oxide, Acne Vulgaris, NADPH oxidase, Hydrogen Peroxide, Keratinocyte, Nitrites, Interleukin, Inflammatory response, and Nitric oxide synthase type II
Research Interests:
Research Interests:
Research Interests: Biology, Immunohistochemistry, Medicine, Biopsy, Syphilis, and 15 moreSerology, Humans, Female, Male, Polymerase Chain Reaction, Skin, Clinical Sciences, Adult, Lipoproteins, INVESTIGATIVE, Amino Acid Sequence, Base Sequence, Sensitivity and Specificity, Clinical Presentation, and Molecular Sequence Data
Research Interests:
Syphilis diagnosis is based on clinical observation, serological analysis, and dark-field microscopy (DFM) detection of Treponema pallidum subsp. pallidum , the etiological agent of syphilis, in skin ulcers. We performed a nested PCR... more
Syphilis diagnosis is based on clinical observation, serological analysis, and dark-field microscopy (DFM) detection of Treponema pallidum subsp. pallidum , the etiological agent of syphilis, in skin ulcers. We performed a nested PCR (nPCR) assay specifically amplifying the tpp47 gene of T. pallidum from swab and blood specimens. We studied a cohort of 294 patients with suspected syphilis and 35 healthy volunteers. Eighty-seven of the 294 patients had primary syphilis, 103 had secondary syphilis, 40 had latent syphilis, and 64 were found not to have syphilis. The T. pallidum nPCR results for swab specimens were highly concordant with syphilis diagnosis, with a sensitivity of 82% and a specificity of 95%. Reasonable agreement was observed between the results obtained with the nPCR and DFM methods (kappa = 0.53). No agreement was found between the nPCR detection of T. pallidum in blood and the diagnosis of syphilis, with sensitivities of 29, 18, 14.7, and 24% and specificities of 96, ...
Research Interests: Virology, Medicine, Clinical Microbiology, Biological Sciences, Syphilis, and 15 moreProspective studies, Humans, Female, Blood, Male, Polymerase Chain Reaction, Treponema, Middle Aged, Adult, Lipoproteins, Molecular Diagnostic Techniques, Sensitivity and Specificity, Sexually Transmitted Disease, Cohort Studies, and Medical and Health Sciences
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Les e. Coli porteurs des fimbriae k88 provoquent des diarrhees chez le porcelet. E. Coli reconnait des glycoconjugues du mucus intestinal et de la surface des enterocytes. La sensibilite a l'infection se transmet selon une segregation... more
Les e. Coli porteurs des fimbriae k88 provoquent des diarrhees chez le porcelet. E. Coli reconnait des glycoconjugues du mucus intestinal et de la surface des enterocytes. La sensibilite a l'infection se transmet selon une segregation mendelienne aboutissant a des phenotypes sensibles (dominants) et resistant (recessif) se traduisant pour le premier par l'adhesion des bacteries aux enterocytes. Nous avons etudie les recepteurs d'e. Coli k88ab sur une population porcine f#2 issus de large white et meishan. Des glycoproteines du mucus, de 42 a 49 kda, sont plus fortement reconnues chez les porcelets resistants que chez les porcelets sensibles. Elles pourraient contribuer a l'elimination des bacteries par le peristaltisme intestinal. En revanche, une glycoproteine de 74 kda, fortement liee a la membrane des enterocytes, est reconnue par e. Coli k88ab, exclusivement chez les porcelets adhesifs ; ce recepteur est une transferrine et elle participe a la definition du phenotype de l'animal. Chez les animaux de phenotype adhesif, la proteine possede un glycanne monosialyle et monofusosyle de type n-acetyllactosaminique alors que la chaine glycannique des serotransferrines sont des hybrides complexes. Ainsi, la glycosylation des transferrines depend du tissu
Research Interests:
Research Interests:
Research Interests:
Diarrheal disease caused by enterotoxigenic Escherichia coli expressing the K88 (F4) fimbrial adhesin (K88 ETEC) is a significant source of mortality and morbidity among newborn and weaned piglets. K88 fimbrial adhesins are filamentous... more
Diarrheal disease caused by enterotoxigenic Escherichia coli expressing the K88 (F4) fimbrial adhesin (K88 ETEC) is a significant source of mortality and morbidity among newborn and weaned piglets. K88 fimbrial adhesins are filamentous surface appendages whose lectin (carbohydrate-binding) activity allows K88 ETEC to attach to specific glycoconjugates (receptors) on porcine intestinal epithelial cells. There are three variants of K88 adhesin (K88ab, K88ac, and K88ad), which possess different, yet related, carbohydrate-binding specificities. We used porcine serum transferrin (pSTf) and purified glycosphingolipids (GSL) to begin to define the minimal recognition sequence for K88 adhesin variants. We found that K88ab adhesin binds with high affinity to pSTf (dissociation constant, 75 μM), while neither K88ac nor K88ad adhesin recognizes pSTf. Degradation of the N-glycan on pSTf by extensive metaperiodate treatment abolished its interaction with the K88ab adhesin, indicating that the K8...