Boualem Sendid - Academia.edu (original) (raw)
Papers by Boualem Sendid
Open Forum Infectious Diseases, 2016
Gut, 2012
We read with great interest the article by Hueber et al 1 reporting on the dramatic failure of se... more We read with great interest the article by Hueber et al 1 reporting on the dramatic failure of secukinumab, an anti-IL17A monoclonal antibody, in Crohn's disease (CD). This multicentre phase IIa study compared secukinumab with placebo in 59 patients with established moderate to severe CD. The study was prematurely stopped because the prespecified criterion for futility was met; for the first time to our knowledge in the history of recent CD trials, a statistical significant difference of mean Crohn's Disease Activity Index (CDAI) (between weeks 4 and 10) was observed in favour of placebo. Of the seven serious adverse events suspected to be drug related, five were worsening of CD, four on secukinumab. The study, thus, clearly showed that pharmacological blockade of IL-17A does not improve CD, but that it could …
Lung, Jan 22, 2017
Mannose-binding lectin (MBL) plays an important role in the innate immune response. In addition t... more Mannose-binding lectin (MBL) plays an important role in the innate immune response. In addition to activating the complement, MBL can induce cytokine production and contribute to a deleterious inflammatory response with severe A(H1N1)pdm09 virus infection. Our aim was to determine if serum MBL levels correlate with the risk of mortality in intensive care units (ICU) patients with A(H1N1)pdm09 infection. Prospective observational study was performed in ICU patients with acute respiratory distress syndrome due to influenza A(H1N1)pdm09 virus. Demographic characteristics and severity indices were recorded at ICU admission. MBL was assayed from blood drawn at influenza diagnosis within 24-48 h following the ICU admission. Outcomes were compared according to MBL levels. Results are expressed as median and interquartile range. Serum MBL levels were studied in 27 patients (age: 56 [IQR 29] years) with severe A(H1N1)pdm09 infection and in 70 healthy controls. Median admission SAPSII and SOF...
Journal de Mycologie Médicale / Journal of Medical Mycology, 2012
Journal de Mycologie Médicale / Journal of Medical Mycology, 2012
Annales de biologie clinique
Beside immunodepression induced by the human immunodeficiency virus, fungal infections of the cen... more Beside immunodepression induced by the human immunodeficiency virus, fungal infections of the central nervous system are extremely rare in heroin-addict patients. We report here a case of meningo-encephalitis with myelo-radicular lesions in a 25-year-old intravenous heroin addict but non-HIV patient, who was admitted for an acute confusion associated with gait disorders. The diagnosis of Candida albicans meningo-encephalo-myelo-radiculitis was established by magnetic resonance imagery and mycological and serological examinations of cerebrospinal fluid. The infection was cured with amphotericin B lipid complex and 5-fluorocytosine. Early diagnosis and antifungal therapy for 6 months resulted in a favorable outcome. The detection of circulating Candida mannan in cerebrospinal fluid with a more sensitive technique combined to MRI were particularly decisive to confirm Candida infection diagnosis, allowing an appropriate antifungal therapy.
Bio tribune magazine, 2011
Dossier 37 La spectrométrie de masse en biologie clinique Résumé : L'identification conventionnel... more Dossier 37 La spectrométrie de masse en biologie clinique Résumé : L'identification conventionnelle (IC) des levures est fondée sur l'utilisation des tests morphologiques, immunologiques et biochimiques (galerie API ® 32 C, bioMérieux). La spectrométrie de masse MALDI-TOF (SM) a été proposée récemment comme nouvelle approche pour l'identification des microorganismes. L'objectif de notre étude était de comparer prospectivement les performances analytiques de la SM et de l'IC pour l'identification des isolats cliniques de levures. En cas de discordance d'identification, le séquençage des régions ITS de l'ADN ribosomal était utilisé comme méthode d'identification de référence. Un total de 1 207 souches a été analysé. Une concordance entre SM et IC a été observée pour 1 105 souches (91,5 %) alors que la proportion de souches différemment identifiées par IC et SM n'était que de 6,1 % (74 souches). Parmi ces 74 identifications discordantes entre SM, l'identification par biologie moléculaire confirmait l'identification obtenue par SM pour 73 isolats (6 %) et celle obtenue par IC pour 1 isolat (0,1 %). Pour les principales espèces d'intérêt médical, les concordances d'identification entre les deux techniques étaient excellentes (entre 98 et 100 %) y compris pour les espèces phylogénétiquement proches (Candida albicans/Candida dubliniensis ; Candida inconspicua/Candida norvegensis ; Candida parapsilosis/Candida metapsilosis/Candida orthopsilosis). La SM n'a été mise en défaut que pour 2,3 % des souches appar tenant aux espèces Candida famata, Candida lambica, Candida magnoliae et aux genres Geotrichum sp. et Trichosporon sp. Nos investigations soulignent le potentiel de la SM pour l'identification des levures et comme alternative fiable, rapide et de moindre coût par rapport aux méthodes conventionnelles. Mots clés : Identification des levures, spectrométrie de masse MALDI TOF, galerie API® 32 C, levures rares
The Analyst, 2013
The interaction of mannose-binding lectins (MBLs) with Candida albicans has been analyzed previou... more The interaction of mannose-binding lectins (MBLs) with Candida albicans has been analyzed previously by microscopy and flow cytometry. We recently demonstrated that serum MBL levels vary during infection with Candida spp. and that serum MBLs are capable of interacting with yeast cell wall components. The aim of this study was to use, for the first time, surface plasmon resonance (SPR) technology to characterize the interaction between living label-free yeasts and non-mutated MBL purified from human serum. Our preliminary results demonstrate the robustness of this tool, which revealed specific and differential reactivities between the principal Candida spp. of medical interest. This model offers new perspectives as a tool for the characterization of yeast strains carrying mutations in gene coding for the mannosylation of fungal cell wall glycans and will enable better characterization of the interactions between C-lectins and glycan motifs expressed on the surface of yeasts.
Pathogens
Cryptococcosis is the third most common cause of invasive fungal infection in solid organ transpl... more Cryptococcosis is the third most common cause of invasive fungal infection in solid organ transplant recipients and cryptococcal meningitis (CM) its main clinical presentation. CM outcomes, as well as its clinical features and radiological characteristics, have not yet been considered on a large scale in the context of kidney transplantation (KT). We performed a nationwide retrospective study of adult patients diagnosed with cryptococcosis after KT between 2002 and 2020 across 30 clinical centers in France. We sought to describe overall and graft survival based on whether KT patients with cryptococcosis developed CM or not. Clinical indicators of CNS involvement and brain radiological characteristics were assessed. Eighty-eight cases of cryptococcosis were diagnosed during the study period, with 61 (69.3%) cases of CM. Mortality was high (32.8%) at 12 months (M12) but not significantly different whether or not patients presented with CM. Baseline hyponatremia and at least one neurol...
Scientific Reports, 2021
Candida albicans mannan consists of a large repertoire of oligomannosides with different types of... more Candida albicans mannan consists of a large repertoire of oligomannosides with different types of mannose linkages and chain lengths, which act as individual epitopes with more or less overlapping antibody specificities. Although anti-C. albicans mannan antibody levels are monitored for diagnostic purposes nothing is known about the qualitative distribution of these antibodies in terms of epitope specificity. We addressed this question using a bank of previously synthesized biotin sulfone tagged oligomannosides (BSTOs) of α and β anomery complemented with a synthetic β-mannotriose described as a protective epitope. The reactivity of these BSTOs was analyzed with IgM isotype monoclonal antibodies (MAbs) of known specificity, polyclonal sera from patients colonized or infected with C. albicans, and mannose binding lectin (MBL). Surface plasmon resonance (SPR) and multiple analyte profiling (MAP) were used. Both methods confirmed the usual reactivity of MAbs against either α or β linka...
Journal of Clinical Microbiology, 2019
This article was published on 26 April 2019 with Malgorzata Mikulska's name incorrectly presented... more This article was published on 26 April 2019 with Malgorzata Mikulska's name incorrectly presented as "Mikulska Malgorzata" in the byline. The byline was updated in the version posted on
International Journal of Molecular Sciences, 2019
Intravenous immunoglobulin (IVIg) therapy has diverse anti-inflammatory and immunomodulatory effe... more Intravenous immunoglobulin (IVIg) therapy has diverse anti-inflammatory and immunomodulatory effects and has been employed successfully in autoimmune and inflammatory diseases. The role of IVIg therapy in the modulation of intestinal inflammation and fungal elimination has not been yet investigated. We studied IVIg therapy in a murine model of dextran sulfate sodium (DSS)-induced colitis. Mice received a single oral inoculum of Candida albicans and were exposed to DSS treatment for 2 weeks to induce colitis. All mice received daily IVIg therapy starting on day 1 for 7 days. IVIg therapy not only prevented a loss of body weight caused by the development of colitis but also reduced the severity of intestinal inflammation, as determined by clinical and histological scores. IVIg treatment significantly reduced the Escherichia coli, Enterococcus faecalis, and C. albicans populations in mice. The beneficial effects of IVIg were associated with the suppression of inflammatory cytokine inte...
Journal of Clinical Microbiology, 2019
Background A mass spectrometry (MS) method that detects a serum disaccharide (MS-DS) was recently... more Background A mass spectrometry (MS) method that detects a serum disaccharide (MS-DS) was recently described for the diagnosis of invasive fungal infections (IFI). We carried out a European collaborative study to evaluate this assay. Methods Patients with IFI were selected according to the availability of sera obtained around the time that IFI was documented: invasive candidiasis (IC; n=26 patients), invasive aspergillosis (IA; n=19), mucormycosis (MM; n=23). Control sera originated from 20 neutropenic patients and 20 patients with bacteraemia. MS-DS was carried out blind to IFI diagnosis. Diagnosis of IC and IA was confirmed by detection of (1,3)-β-D-glucan (BDG), mannan (Man) and galactomannan (GM), respectively. MM was detected by q-PCR. Results All tests discriminated IC sera from controls with bacteraemia (P≤0.0009). MS-DS sensitivity and specificity were 51% and 87%, respectively. MS-DS complemented the high specificity of Man monitoring. All tests discriminated IA sera from ne...
Gut pathogens, 2017
Toll-like receptors (TLRs) are the major pattern recognition receptors that mediate sensing of a ... more Toll-like receptors (TLRs) are the major pattern recognition receptors that mediate sensing of a wide range of microorganisms. TLR2 forms heterodimers with either TLR1 or TLR6, broadening its ligand diversity against pathogens. TLR1, TLR2 and TLR6 have been implicated in the recognition of Candida albicans, an opportunistic fungal pathogen that colonizes the gastrointestinal tract. In this study, we explored whether the deficiency in TLR1, TLR2 or TLR6 impacts C. albicans colonization and inflammation-associated colonic injury in the dextran sulfate sodium (DSS)-induced colitis in mice. DSS treatment and C. albicans challenge induced greater weight loss, worse clinical signs of inflammation, higher histopathologic scores, and increased mortality rates in TLR1(-/-) and TLR2(-/-) mice when compared to TLR6(-/-) and wild-type mice. The number of C. albicans colonies in the stomach, colon and feces was decreased in TLR6(-/-) mice as compared to TLR2(-/-), TLR1(-/-) and wild-type mice. I...
American Journal of Physiology - Heart and Circulatory Physiology, 2016
Platelets are capable of binding, aggregating, and internalizing microorganisms, which enhances t... more Platelets are capable of binding, aggregating, and internalizing microorganisms, which enhances the elimination of pathogens from the blood. The yeast Candida albicans is a pathobiont causing life-threatening invasive infections. Its cell wall contains β-1,3 glucans that are known to trigger a wide range of host cell activities and to circulate during infection. We studied the effect of β-1,3 glucan fractions (BGFs) consisting of diglucosides (Glc2), tetraglucosides (Glc4), and pentaglucosides (Glc5) on human platelets, their mechanisms of action, and their possible impact on host defenses. The effect of BGFs on the coagulation process was determined by measuring thrombin generation. Platelets pretreated with BGFs were analyzed in terms of activation, receptor expression, aggregation, and adhesion to neutrophils and to C. albicans. The results show that BGFs affected the endogenous thrombin potential in a concentration-dependent manner. For platelet activation, BGFs at a low concent...
Réanimation, 2014
appears interesting to follow-up. The use of these biomarkers for preemptive treatments or at the... more appears interesting to follow-up. The use of these biomarkers for preemptive treatments or at the opposite to decrease the number of empiric prescriptions may help rationalizing antifungal management and increasing the rapidity of treatment administration. Further progresses are expected, relying on new molecular targets and assays based on new biotechnologies.
Glycobiology, 2015
β-1,2-Linked mannosides are expressed on numerous cell-wall glycoconjugates of the opportunistic ... more β-1,2-Linked mannosides are expressed on numerous cell-wall glycoconjugates of the opportunistic pathogen yeast Candida albicans. Several studies evidenced their implication in the host-pathogen interaction and virulence mechanisms. In the present study, we characterized the in vitro activity of CaBmt3, a β-1,2-mannosyltransferase involved in the elongation of β-1,2-oligomannosides oligomers onto the cell-wall polymannosylated N-glycans. A recombinant soluble enzyme Bmt3p was produced in Pichia pastoris and its enzyme activity was investigated using natural and synthetic oligomannosides as potential acceptor substrates. Bmt3p was shown to exhibit an exquisite enzymatic specificity by adding a single terminal β-mannosyl residue to α-1,2-linked oligomannosides capped by a Manβ1-2Man motif. Furthermore, we demonstrated that the previously identified CaBmt1 and CaBmt3 efficiently act together to generate Manβ1-2Manβ1-2[Manα1-2] n sequence from α-1,2-linked oligomannosides onto exogenous and endogenous substrates.
Journal de Mycologie Médicale / Journal of Medical Mycology, 2015
Introduction Les levuroses invasives sont des infections graves et difficiles a diagnostiquer che... more Introduction Les levuroses invasives sont des infections graves et difficiles a diagnostiquer chez le nouveau-ne. Les signes cliniques ne sont pas specifiques et le rendement des hemocultures est tres faible. Le dosage des s-(1,3)-D-glucanes (BDG) seriques constitue un marqueur interessant pour le diagnostic des infections fongiques invasives de l’adulte. Notre objectif etait d’evaluer les performances diagnostiques de ce test dans les levuroses invasives neonatales et son apport dans le suivi therapeutique. Patients et methodes Une etude retrospective a ete realisee dans le service de neonatalogie du CHU d’Amiens de fevrier 2012 a fevrier 2014. Resultats Quarante-sept nouveau-nes (33 garcons, 14 filles) d’âge gestationnel median de 30 (27 ; 31) semaines et de poids de naissance median de 1200 (968 ; 1700) grammes ont ete inclus et repartis en 3 groupes : 21 nouveau-nes temoins (groupe CTRL), 20 nouveau-nes ayant une levurose probable (groupe PB) (13 candidoses et 7 malassezioses) et 6 nouveau-nes ayant une levurose prouvee (groupe PV) (4 candidoses et 2 malassezioses). Le taux median de BDG etait plus eleve dans le groupe des levuroses invasives (PB + PV) : 149 (85 ; 364) vs le groupe CTRL 39 (20 ; 94) pg/mL ; p Conclusion Nos resultats sont en faveur de l’utilite de la glucanemie dans le diagnostic et le suivi therapeutique des levuroses invasives neonatales. Cet outil devrait permettre d’identifier precocement les patients justifiant d’un traitement antifongique.
Open Forum Infectious Diseases, 2016
Gut, 2012
We read with great interest the article by Hueber et al 1 reporting on the dramatic failure of se... more We read with great interest the article by Hueber et al 1 reporting on the dramatic failure of secukinumab, an anti-IL17A monoclonal antibody, in Crohn's disease (CD). This multicentre phase IIa study compared secukinumab with placebo in 59 patients with established moderate to severe CD. The study was prematurely stopped because the prespecified criterion for futility was met; for the first time to our knowledge in the history of recent CD trials, a statistical significant difference of mean Crohn's Disease Activity Index (CDAI) (between weeks 4 and 10) was observed in favour of placebo. Of the seven serious adverse events suspected to be drug related, five were worsening of CD, four on secukinumab. The study, thus, clearly showed that pharmacological blockade of IL-17A does not improve CD, but that it could …
Lung, Jan 22, 2017
Mannose-binding lectin (MBL) plays an important role in the innate immune response. In addition t... more Mannose-binding lectin (MBL) plays an important role in the innate immune response. In addition to activating the complement, MBL can induce cytokine production and contribute to a deleterious inflammatory response with severe A(H1N1)pdm09 virus infection. Our aim was to determine if serum MBL levels correlate with the risk of mortality in intensive care units (ICU) patients with A(H1N1)pdm09 infection. Prospective observational study was performed in ICU patients with acute respiratory distress syndrome due to influenza A(H1N1)pdm09 virus. Demographic characteristics and severity indices were recorded at ICU admission. MBL was assayed from blood drawn at influenza diagnosis within 24-48 h following the ICU admission. Outcomes were compared according to MBL levels. Results are expressed as median and interquartile range. Serum MBL levels were studied in 27 patients (age: 56 [IQR 29] years) with severe A(H1N1)pdm09 infection and in 70 healthy controls. Median admission SAPSII and SOF...
Journal de Mycologie Médicale / Journal of Medical Mycology, 2012
Journal de Mycologie Médicale / Journal of Medical Mycology, 2012
Annales de biologie clinique
Beside immunodepression induced by the human immunodeficiency virus, fungal infections of the cen... more Beside immunodepression induced by the human immunodeficiency virus, fungal infections of the central nervous system are extremely rare in heroin-addict patients. We report here a case of meningo-encephalitis with myelo-radicular lesions in a 25-year-old intravenous heroin addict but non-HIV patient, who was admitted for an acute confusion associated with gait disorders. The diagnosis of Candida albicans meningo-encephalo-myelo-radiculitis was established by magnetic resonance imagery and mycological and serological examinations of cerebrospinal fluid. The infection was cured with amphotericin B lipid complex and 5-fluorocytosine. Early diagnosis and antifungal therapy for 6 months resulted in a favorable outcome. The detection of circulating Candida mannan in cerebrospinal fluid with a more sensitive technique combined to MRI were particularly decisive to confirm Candida infection diagnosis, allowing an appropriate antifungal therapy.
Bio tribune magazine, 2011
Dossier 37 La spectrométrie de masse en biologie clinique Résumé : L'identification conventionnel... more Dossier 37 La spectrométrie de masse en biologie clinique Résumé : L'identification conventionnelle (IC) des levures est fondée sur l'utilisation des tests morphologiques, immunologiques et biochimiques (galerie API ® 32 C, bioMérieux). La spectrométrie de masse MALDI-TOF (SM) a été proposée récemment comme nouvelle approche pour l'identification des microorganismes. L'objectif de notre étude était de comparer prospectivement les performances analytiques de la SM et de l'IC pour l'identification des isolats cliniques de levures. En cas de discordance d'identification, le séquençage des régions ITS de l'ADN ribosomal était utilisé comme méthode d'identification de référence. Un total de 1 207 souches a été analysé. Une concordance entre SM et IC a été observée pour 1 105 souches (91,5 %) alors que la proportion de souches différemment identifiées par IC et SM n'était que de 6,1 % (74 souches). Parmi ces 74 identifications discordantes entre SM, l'identification par biologie moléculaire confirmait l'identification obtenue par SM pour 73 isolats (6 %) et celle obtenue par IC pour 1 isolat (0,1 %). Pour les principales espèces d'intérêt médical, les concordances d'identification entre les deux techniques étaient excellentes (entre 98 et 100 %) y compris pour les espèces phylogénétiquement proches (Candida albicans/Candida dubliniensis ; Candida inconspicua/Candida norvegensis ; Candida parapsilosis/Candida metapsilosis/Candida orthopsilosis). La SM n'a été mise en défaut que pour 2,3 % des souches appar tenant aux espèces Candida famata, Candida lambica, Candida magnoliae et aux genres Geotrichum sp. et Trichosporon sp. Nos investigations soulignent le potentiel de la SM pour l'identification des levures et comme alternative fiable, rapide et de moindre coût par rapport aux méthodes conventionnelles. Mots clés : Identification des levures, spectrométrie de masse MALDI TOF, galerie API® 32 C, levures rares
The Analyst, 2013
The interaction of mannose-binding lectins (MBLs) with Candida albicans has been analyzed previou... more The interaction of mannose-binding lectins (MBLs) with Candida albicans has been analyzed previously by microscopy and flow cytometry. We recently demonstrated that serum MBL levels vary during infection with Candida spp. and that serum MBLs are capable of interacting with yeast cell wall components. The aim of this study was to use, for the first time, surface plasmon resonance (SPR) technology to characterize the interaction between living label-free yeasts and non-mutated MBL purified from human serum. Our preliminary results demonstrate the robustness of this tool, which revealed specific and differential reactivities between the principal Candida spp. of medical interest. This model offers new perspectives as a tool for the characterization of yeast strains carrying mutations in gene coding for the mannosylation of fungal cell wall glycans and will enable better characterization of the interactions between C-lectins and glycan motifs expressed on the surface of yeasts.
Pathogens
Cryptococcosis is the third most common cause of invasive fungal infection in solid organ transpl... more Cryptococcosis is the third most common cause of invasive fungal infection in solid organ transplant recipients and cryptococcal meningitis (CM) its main clinical presentation. CM outcomes, as well as its clinical features and radiological characteristics, have not yet been considered on a large scale in the context of kidney transplantation (KT). We performed a nationwide retrospective study of adult patients diagnosed with cryptococcosis after KT between 2002 and 2020 across 30 clinical centers in France. We sought to describe overall and graft survival based on whether KT patients with cryptococcosis developed CM or not. Clinical indicators of CNS involvement and brain radiological characteristics were assessed. Eighty-eight cases of cryptococcosis were diagnosed during the study period, with 61 (69.3%) cases of CM. Mortality was high (32.8%) at 12 months (M12) but not significantly different whether or not patients presented with CM. Baseline hyponatremia and at least one neurol...
Scientific Reports, 2021
Candida albicans mannan consists of a large repertoire of oligomannosides with different types of... more Candida albicans mannan consists of a large repertoire of oligomannosides with different types of mannose linkages and chain lengths, which act as individual epitopes with more or less overlapping antibody specificities. Although anti-C. albicans mannan antibody levels are monitored for diagnostic purposes nothing is known about the qualitative distribution of these antibodies in terms of epitope specificity. We addressed this question using a bank of previously synthesized biotin sulfone tagged oligomannosides (BSTOs) of α and β anomery complemented with a synthetic β-mannotriose described as a protective epitope. The reactivity of these BSTOs was analyzed with IgM isotype monoclonal antibodies (MAbs) of known specificity, polyclonal sera from patients colonized or infected with C. albicans, and mannose binding lectin (MBL). Surface plasmon resonance (SPR) and multiple analyte profiling (MAP) were used. Both methods confirmed the usual reactivity of MAbs against either α or β linka...
Journal of Clinical Microbiology, 2019
This article was published on 26 April 2019 with Malgorzata Mikulska's name incorrectly presented... more This article was published on 26 April 2019 with Malgorzata Mikulska's name incorrectly presented as "Mikulska Malgorzata" in the byline. The byline was updated in the version posted on
International Journal of Molecular Sciences, 2019
Intravenous immunoglobulin (IVIg) therapy has diverse anti-inflammatory and immunomodulatory effe... more Intravenous immunoglobulin (IVIg) therapy has diverse anti-inflammatory and immunomodulatory effects and has been employed successfully in autoimmune and inflammatory diseases. The role of IVIg therapy in the modulation of intestinal inflammation and fungal elimination has not been yet investigated. We studied IVIg therapy in a murine model of dextran sulfate sodium (DSS)-induced colitis. Mice received a single oral inoculum of Candida albicans and were exposed to DSS treatment for 2 weeks to induce colitis. All mice received daily IVIg therapy starting on day 1 for 7 days. IVIg therapy not only prevented a loss of body weight caused by the development of colitis but also reduced the severity of intestinal inflammation, as determined by clinical and histological scores. IVIg treatment significantly reduced the Escherichia coli, Enterococcus faecalis, and C. albicans populations in mice. The beneficial effects of IVIg were associated with the suppression of inflammatory cytokine inte...
Journal of Clinical Microbiology, 2019
Background A mass spectrometry (MS) method that detects a serum disaccharide (MS-DS) was recently... more Background A mass spectrometry (MS) method that detects a serum disaccharide (MS-DS) was recently described for the diagnosis of invasive fungal infections (IFI). We carried out a European collaborative study to evaluate this assay. Methods Patients with IFI were selected according to the availability of sera obtained around the time that IFI was documented: invasive candidiasis (IC; n=26 patients), invasive aspergillosis (IA; n=19), mucormycosis (MM; n=23). Control sera originated from 20 neutropenic patients and 20 patients with bacteraemia. MS-DS was carried out blind to IFI diagnosis. Diagnosis of IC and IA was confirmed by detection of (1,3)-β-D-glucan (BDG), mannan (Man) and galactomannan (GM), respectively. MM was detected by q-PCR. Results All tests discriminated IC sera from controls with bacteraemia (P≤0.0009). MS-DS sensitivity and specificity were 51% and 87%, respectively. MS-DS complemented the high specificity of Man monitoring. All tests discriminated IA sera from ne...
Gut pathogens, 2017
Toll-like receptors (TLRs) are the major pattern recognition receptors that mediate sensing of a ... more Toll-like receptors (TLRs) are the major pattern recognition receptors that mediate sensing of a wide range of microorganisms. TLR2 forms heterodimers with either TLR1 or TLR6, broadening its ligand diversity against pathogens. TLR1, TLR2 and TLR6 have been implicated in the recognition of Candida albicans, an opportunistic fungal pathogen that colonizes the gastrointestinal tract. In this study, we explored whether the deficiency in TLR1, TLR2 or TLR6 impacts C. albicans colonization and inflammation-associated colonic injury in the dextran sulfate sodium (DSS)-induced colitis in mice. DSS treatment and C. albicans challenge induced greater weight loss, worse clinical signs of inflammation, higher histopathologic scores, and increased mortality rates in TLR1(-/-) and TLR2(-/-) mice when compared to TLR6(-/-) and wild-type mice. The number of C. albicans colonies in the stomach, colon and feces was decreased in TLR6(-/-) mice as compared to TLR2(-/-), TLR1(-/-) and wild-type mice. I...
American Journal of Physiology - Heart and Circulatory Physiology, 2016
Platelets are capable of binding, aggregating, and internalizing microorganisms, which enhances t... more Platelets are capable of binding, aggregating, and internalizing microorganisms, which enhances the elimination of pathogens from the blood. The yeast Candida albicans is a pathobiont causing life-threatening invasive infections. Its cell wall contains β-1,3 glucans that are known to trigger a wide range of host cell activities and to circulate during infection. We studied the effect of β-1,3 glucan fractions (BGFs) consisting of diglucosides (Glc2), tetraglucosides (Glc4), and pentaglucosides (Glc5) on human platelets, their mechanisms of action, and their possible impact on host defenses. The effect of BGFs on the coagulation process was determined by measuring thrombin generation. Platelets pretreated with BGFs were analyzed in terms of activation, receptor expression, aggregation, and adhesion to neutrophils and to C. albicans. The results show that BGFs affected the endogenous thrombin potential in a concentration-dependent manner. For platelet activation, BGFs at a low concent...
Réanimation, 2014
appears interesting to follow-up. The use of these biomarkers for preemptive treatments or at the... more appears interesting to follow-up. The use of these biomarkers for preemptive treatments or at the opposite to decrease the number of empiric prescriptions may help rationalizing antifungal management and increasing the rapidity of treatment administration. Further progresses are expected, relying on new molecular targets and assays based on new biotechnologies.
Glycobiology, 2015
β-1,2-Linked mannosides are expressed on numerous cell-wall glycoconjugates of the opportunistic ... more β-1,2-Linked mannosides are expressed on numerous cell-wall glycoconjugates of the opportunistic pathogen yeast Candida albicans. Several studies evidenced their implication in the host-pathogen interaction and virulence mechanisms. In the present study, we characterized the in vitro activity of CaBmt3, a β-1,2-mannosyltransferase involved in the elongation of β-1,2-oligomannosides oligomers onto the cell-wall polymannosylated N-glycans. A recombinant soluble enzyme Bmt3p was produced in Pichia pastoris and its enzyme activity was investigated using natural and synthetic oligomannosides as potential acceptor substrates. Bmt3p was shown to exhibit an exquisite enzymatic specificity by adding a single terminal β-mannosyl residue to α-1,2-linked oligomannosides capped by a Manβ1-2Man motif. Furthermore, we demonstrated that the previously identified CaBmt1 and CaBmt3 efficiently act together to generate Manβ1-2Manβ1-2[Manα1-2] n sequence from α-1,2-linked oligomannosides onto exogenous and endogenous substrates.
Journal de Mycologie Médicale / Journal of Medical Mycology, 2015
Introduction Les levuroses invasives sont des infections graves et difficiles a diagnostiquer che... more Introduction Les levuroses invasives sont des infections graves et difficiles a diagnostiquer chez le nouveau-ne. Les signes cliniques ne sont pas specifiques et le rendement des hemocultures est tres faible. Le dosage des s-(1,3)-D-glucanes (BDG) seriques constitue un marqueur interessant pour le diagnostic des infections fongiques invasives de l’adulte. Notre objectif etait d’evaluer les performances diagnostiques de ce test dans les levuroses invasives neonatales et son apport dans le suivi therapeutique. Patients et methodes Une etude retrospective a ete realisee dans le service de neonatalogie du CHU d’Amiens de fevrier 2012 a fevrier 2014. Resultats Quarante-sept nouveau-nes (33 garcons, 14 filles) d’âge gestationnel median de 30 (27 ; 31) semaines et de poids de naissance median de 1200 (968 ; 1700) grammes ont ete inclus et repartis en 3 groupes : 21 nouveau-nes temoins (groupe CTRL), 20 nouveau-nes ayant une levurose probable (groupe PB) (13 candidoses et 7 malassezioses) et 6 nouveau-nes ayant une levurose prouvee (groupe PV) (4 candidoses et 2 malassezioses). Le taux median de BDG etait plus eleve dans le groupe des levuroses invasives (PB + PV) : 149 (85 ; 364) vs le groupe CTRL 39 (20 ; 94) pg/mL ; p Conclusion Nos resultats sont en faveur de l’utilite de la glucanemie dans le diagnostic et le suivi therapeutique des levuroses invasives neonatales. Cet outil devrait permettre d’identifier precocement les patients justifiant d’un traitement antifongique.