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Accueil > Départements > Microbiologie > Pierre TISSIERES : Endotoxines, Structures et Réponses de l’hôte

Publications de l’équipe


  • G. Agbota, N. Fievet, B. Heude, M. Accrombessi, U. Ahouayito, E. Yovo, D. Dossa, L. Dramane, A. Gartner, S. Ezinmègnon, J. Yugueros Marcos, L. Vachot, P. Tissières, A. Massougbodji, Y. Martin-Prével, M. Cot, et V. Briand, « Poor maternal anthropometric status before conception is associated with a deleterious infant growth during the first year of life: a longitudinal preconceptional cohort », Pediatric Obesity, août 2019.
    Résumé : BACKGROUND: According to the Developmental Origins of Health and Diseases concept, exposures in the preconception period may be critical. For the first time, we evaluated the effect of preconception poor anthropometric status on infant's growth in sub-Saharan Africa. METHODS: A mother-child cohort was followed prospectively from preconception to 1 year old in Benin. Maternal anthropometric status was assessed by prepregnancy body mass index (BMI), approximated by BMI at the first antenatal visit before 7 weeks' gestation, and gestational weight gain (GWG). BMI was categorized as underweight, normal, overweight, and obesity according to World Health Organization standards. GWG was categorized as low (<7 kg), mild (7-12 kg), and high (>12 kg). In infant, stunting and wasting were defined as length-for-age and weight-for-length z scores less than -2 SD, respectively. We evaluated the association between BMI/GWG and infant's weight and length at birth and during the first year of life, as well as with stunting and wasting at 12 months using mixed linear and logistic regression models. RESULTS: In multivariate, preconceptional underweight was associated with a lower infant's weight at birth and during the first year (-164 g; 95% CI, -307 to -22; and -342 g; 95% CI, -624 to -61, respectively) and with a higher risk of stunting at 12 months (adjusted odds ratio [aOR] = 3.98; 95% CI, 1.01-15.85). Furthermore, preconceptional obesity and a high GWG were associated with a higher weight and length at birth and during the first year. CONCLUSION: Underweight and obesity before conception as well as GWG were associated with infant's growth. These results argue for preventive interventions starting as early as the preconception period to support child long-term health.
    Mots-clés : ESHR, infant growth, maternal anthropometric status, MICROBIO, Preconceptional cohort study, pregnancy.

  • G. Agbota, K. Polman, F. T. Wieringa, M. Campos-Ponce, M. Accrombessi, E. Yovo, C. Roucher, S. Ezinmègnon, J. Y. Marcos, L. Vachot, P. Tissières, A. Massougbodji, N. Fievet, M. Cot, et V. Briand, « Maternal malaria but not schistosomiasis is associated with a higher risk of febrile infection in infant during the first 3 months of life: A mother-child cohort in Benin », PloS One, vol. 14, nᵒ 9, p. e0222864, 2019.
    Résumé : BACKGROUND: Malaria and schistosomiasis represent two of the most prevalent and disabling parasitic infections in developing countries. Few studies have evaluated the effect of maternal schistosomiasis and malaria in the peri-conceptional period on infant's risk of infection. METHODS: In Benin, women were followed from the preconception period until delivery. Subsequently, their children were followed from birth to 3 months of age. Pre-pregnancy malaria, malaria in pregnancy (MiP)-determined monthly using a thick blood smear-and urinary schistosomiasis-determined once before pregnancy and once at delivery using urine filtration-were the main maternal exposures. Infant's febrile infection (fever with respiratory, gastrointestinal and/or cutaneous clinical signs anytime during follow-up) was the main outcome. In a secondary analysis, we checked the relation of malaria and schistosomiasis with infant's hemoglobin (Hb) concentration. Both effects were separately assessed using logistic/mixed linear regression models. RESULTS: The prevalence of MiP was 35.7% with 10.8% occurring during the 1st trimester, and the prevalence of schistosomiasis was 21.8%. From birth to 3 months, 25.3% of infants had at least one episode of febrile infection. In multivariate analysis, MiP, particularly malaria in the 1st trimester, was significantly associated with a higher risk of infant's febrile infection (aOR = 4.99 [1.1; 22.6], p = 0.03). In secondary results, pre-pregnancy malaria and schistosomiasis were significantly associated with a lower infant's Hb concentration during the first 3 months. CONCLUSION: We evidenced the deleterious effect of maternal parasitic infections on infant's health. Our results argue in favor of the implementation of preventive strategies as early as in the peri-conception.
    Mots-clés : ESHR, MICROBIO.

  • G. Briassoulis, P. Briassoulis, M. Miliaraki, S. Ilia, M. Parlato, F. Philippart, A. Rouquette, V. Moucadel, J. - M. Cavaillon, B. Misset, et Combined Approach for The eArly diagnosis of INfection in sepsis (CAPTAIN) study group, « Biomarker cruises in sepsis: who is the CAPTAIN? Discussion on "Circulating biomarkers may be unable to detect infection at the early phase of sepsis in ICU patients: the CAPTAIN prospective multicenter cohort study" », Intensive Care Medicine, janv. 2019.

  • V. Dell'Orto, R. Raschetti, R. Centorrino, A. Montane, P. Tissieres, N. Yousef, et D. De Luca, « Short- and long-term respiratory outcomes in neonates with ventilator-associated pneumonia », Pediatric Pulmonology, août 2019.
    Résumé : BACKGROUND AND OBJECTIVE: Ventilator-associated pneumonia (VAP) is a common nosocomial infection in critical care settings and might have important long-term consequences in neonates. Our aim is to clarify the short- and long-term respiratory outcomes of neonates affected by VAP. METHODS: Prospective, population-based, cohort study with 12 months follow-up based on clinical examinations and diary-based respiratory morbidity score, conducted in an academic tertiary referral neonatal unit with dedicated follow-up program. RESULTS: A total of 199 inborn neonates consecutively ventilated for at least 48 hours were eligible for the study. One hundred fifty-one were finally enrolled and classified as "exposed" or "unexposed" to VAP, if they fulfilled (or not) VAP criteria once during their stay. Bronchopulmonary dysplasia (BPD) incidence was significantly higher in exposed (75%) than in unexposed babies (26.8%; relative risk [RR]: 2.8 [1.9-4.0]; Adj RR: 3.5 [1.002-12.7]; P = .049; number needed to harm = 2.07), although the composite BPD/mortality did not differ. Exposed patients showed longer intensive care unit stay (87 [43-116] vs 14 [8-52] days; St.β = 0.24; P < .0001) and duration of ventilation (15 [10-25] vs 5 [4-8] days; St.β = 0.29; P < .0001) than unexposed neonates. Exposed patients also showed less ventilator-free days (11 [5-17.7] vs 22 [14-24] days; St.β = -0.15; P = .05) compared to unexposed. Respiratory infections, use of drugs, rehospitalization for respiratory reasons, home oxygen therapy, their composite outcome, and diary-based clinical respiratory morbidity score were similar between the cohorts. CONCLUSION: Neonatal VAP seems associated to higher incidence of BPD, longer ventilation, and intensive care stay but it does not affect long-term respiratory morbidity.
    Mots-clés : ESHR, follow-up, MICROBIO, neonate, respiratory morbidity, ventilator-associated pneumonia.

  • P. Durand, D. De Luca, et P. Tissieres, « What's new in lung ultrasound in the critically ill or injured child », Intensive Care Medicine, vol. 45, nᵒ 4, p. 508-511, avr. 2019.
    Mots-clés : chest radiography, ESHR, infants, MICROBIO, pneumonia, ultrasonography, ventilation.

  • L. Morin, M. Kneyber, N. J. G. Jansen, M. J. Peters, E. Javouhey, S. Nadel, G. Maclaren, L. J. Schlapbach, P. Tissieres, et ESPNIC Refractory Septic Shock Definition taskforce and the Infection, Systemic Inflammation and Sepsis ESPNIC section, « Translational gap in pediatric septic shock management: an ESPNIC perspective », Annals of Intensive Care, vol. 9, nᵒ 1, p. 73, juin 2019.
    Résumé : BACKGROUND: The Surviving Sepsis Campaign and the American College of Critical Care Medicine guidelines have provided recommendations for the management of pediatric septic shock patients. We conducted a survey among the European Society of Pediatric and Neonatal Intensive Care (ESPNIC) members to assess variations to these recommendations. METHODS: A total of 114 pediatric intensive care physicians completed an electronic survey. The survey consisted of four standardized clinical cases exploring seven clinical scenarios. RESULTS: Among the seven different clinical scenarios, the types of fluids were preferentially non-synthetic colloids (albumin) and crystalloids (isotonic saline) and volume expansion was not limited to 60 ml/kg. Early intubation for mechanical ventilation was used by 70% of the participants. Norepinephrine was stated to be used in 94% of the PICU physicians surveyed, although dopamine or epinephrine is recommended as first-line vasopressors in pediatric septic shock. When norepinephrine was used, the addition of another inotrope was frequent. Specific drugs such as vasopressin or enoximone were used in < 20%. Extracorporeal life support was used or considered by 91% of the physicians audited in certain specific situations, whereas the use of high-flow hemofiltration was considered for 44%. CONCLUSIONS: This pediatric septic shock management survey outlined variability in the current clinician-reported practice of pediatric septic shock management. As most recommendations are not supported by evidence, these findings outline some limitation of existing pediatric guidelines in regard to context and patient's specificity.
    Mots-clés : ESHR, MICROBIO.

  • A. Novikov, N. Marr, et M. Caroff, « A comparative study of the complete lipopolysaccharide structures and biosynthesis loci of Bordetella avium, B. hinzii, and B. trematum », Biochimie, vol. 159, p. 81-92, avr. 2019.
    Résumé : A dozen species of human and animal pathogens have been described to date in the Bordetella genus, with the majority being respiratory tract pathogens. Bordetella avium lipopolysaccharides have been shown to be important virulence factors for this bird pathogen. B. hinzii is closely related to the B. avium species, but has also been isolated from humans. B. trematum is associated to ear and blood infections in humans. Its lipid A structure, the biological active moiety of LPS, was found to be closely related to those of B. avium and B. hinzii. It is important to unveil the subtle structural modifications orchestrated during the LPS biosynthetic pathway to better understand host adaptation. The present data are also important in the context of deciphering the virulence pathways of this important genus containing the major pathogens B. pertussis and B. parapertussis, responsible for whooping cough. We recently reported the isolated lipid A structures of the three presented species, following the previously identified O-chain structures. In the present study, we provide details on the free and O-chain-linked core oligosaccharides which were required to characterize the complete LPS structures. Data are presented here in relation to relevant biosynthesis genes. The present characterization of the three species is well illustrated by Matrix Assisted Laser Desorption Mass Spectrometry experiments, and data were obtained mainly on native LPS molecules for the first time. (C) 2018 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved.
    Mots-clés : antigen, B. hinzii, B. trematum, B. hinzii, B. trematum, Bordetella avium, bronchiseptica, chain linkage region, core, desorption mass-spectrometry, Endotoxin, ESHR, Genomics, Lipopolysaccharide MALDI MS, MICROBIO, o-specific polysaccharide, parapertussis, pertussis, sp nov., takamatsuzuka tumulus.

  • W. Zhang-Sun, F. Terce, R. Burcelin, A. Novikov, M. Serino, et M. Caroff, « Structure function relationships in three lipids A from the Ralstonia genus rising in obese patients », Biochimie, vol. 159, p. 72-80, avr. 2019.
    Résumé : The identification of a functional molecular moiety relating the lipopolysaccharides (LPSs) to their capacity to induce inflammation-mediated metabolic diseases needed to be performed. We previously described a proportional increase in the relative abundance of the 16 SrDNA bacterial gene from the genus Ralstonia, within the microbiota from the adipose tissue stroma vascular fraction of obese patients, suggesting a causal role of the bacteria. Therefore, we first characterized the structures of the lipids A, the inflammatory inducing moieties of LPSs, of three Ralstonia species: Ralstonia eutropha, R. mannitolilytica and R. pickettii, and then compared each, in terms of in vitro inflammatory capacities. R. pickettii lipid A displaying only 5 Fatty Acids (FA) was a weaker inducer of inflammation, compared to the two other species harboring hexa-acylated lipids A, despite the presence of 2 AraN substituents on the phosphate groups. With regard to in vitro pro-inflammatory activities, TNF-alpha and IL-6 inducing capacities were compared on THP-1 cells treated with LPSs isolated from the three Ralstonia. R. pickettii, with low inflammatory capacities, and recently involved in nosocomial outcomes, could explain the low inflammatory level reported in previous studies on diabetic patients and animals. In addition, transmission electron microscopy was performed on the three Ralstonia species. It showed that the R. pickettii under-acylated LPSs, with a higher level of phosphate substitution had the capacity of producing more outer membrane vesicles (OMVs). The latter could facilitate transfer of LPSs to the blood and explain the increased low-grade inflammation observed in obese/diabetic patients. (C) 2019 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved.
    Mots-clés : bacteria, Cytokines, endotoxemia, ESHR, Lipopolysaccharide, lipopolysaccharides, lps, Mass spectrometry, Metabolic diseases, MICROBIO, microextraction, onset, phosphate groups, Ralstonia, strains, Structure.


  • G. Agbota, M. Accrombessi, S. Ezinmegnon, U. Ahouayito, B. Agossou, A. Massougbodji, L. Ganee, J. Marcos, A. Pachot, P. Tissieres, N. Fievet, M. Cot, et V. Briand, « Malaria in the First Trimester of Pregnancy Is Associated with Non-Malaria Fever During the First Three Months of Life in a Beninese Infant Population », American Journal of Tropical Medicine and Hygiene, vol. 99, nᵒ 4, p. 235-235, 2018.

  • N. Kieffer, P. Nordmann, A. M. Moreno, L. Z. Moreno, R. Chaby, A. Breton, P. Tissières, et L. Poirel, « Genetic and functional characterization of an MCR-3-like producing Escherichia coli recovered from swine, Brazil », Antimicrobial Agents and Chemotherapy, avr. 2018.
    Résumé : A collection of 126 pigs were screened for carriage of colistin-resistant Enterobacteriaceae in a farm in Minas Gerais, Brazil. Out of this collection, eigth colistin-resistant Escherichia coli isolates were recovered, including one from Minas Gerais State, producing a new MCR-3 variant (MCR-3.12). Analysis of the lipopolysaccharide revealed that MCR-3.12 had a similar function as MCR-1 and MCR-2 by adding a phosphoethanolamine group to the lipid A. Genetic analysis showed that the mcr-3.12 gene was carried by an IncA/C2 plasmid and was embedded in an original genetic environment. This study reports the occurrence of the MCR-3-like determinant in South America and firstly demonstrates the functionality of this group of enzymes as a phosphoethanolamine transferase.
    Mots-clés : ESHR, MICROBIO.

  • M. Parlato, F. Philippart, A. Rouquette, V. Moucadel, V. Puchois, S. Blein, J. - P. Bedos, J. - L. Diehl, O. Hamzaoui, D. Annane, D. Journois, M. Ben Boutieb, L. Estève, C. Fitting, J. - M. Treluyer, A. Pachot, M. Adib-Conquy, J. - M. Cavaillon, B. Misset, et Captain Study Group, « Circulating biomarkers may be unable to detect infection at the early phase of sepsis in ICU patients: the CAPTAIN prospective multicenter cohort study », Intensive Care Medicine, juin 2018.
    Résumé : PURPOSE: Sepsis and non-septic systemic inflammatory response syndrome (SIRS) are the same syndromes, differing by their cause, sepsis being secondary to microbial infection. Microbiological tests are not enough to detect infection early. While more than 50 biomarkers have been proposed to detect infection, none have been repeatedly validated. AIM: To assess the accuracy of circulating biomarkers to discriminate between sepsis and non-septic SIRS. METHODS: The CAPTAIN study was a prospective observational multicenter cohort of 279 ICU patients with hypo- or hyperthermia and criteria of SIRS, included at the time the attending physician considered antimicrobial therapy. Investigators collected blood at inclusion to measure 29 plasma compounds and ten whole blood RNAs, and-for those patients included within working hours-14 leukocyte surface markers. Patients were classified as having sepsis or non-septic SIRS blindly to the biomarkers results. We used the LASSO method as the technique of multivariate analysis, because of the large number of biomarkers. RESULTS: During the study period, 363 patients with SIRS were screened, 84 having exclusion criteria. Ninety-one patients were classified as having non-septic SIRS and 188 as having sepsis. Eight biomarkers had an area under the receiver operating curve (ROC-AUC) over 0.6 with a 95% confidence interval over 0.5. LASSO regression identified CRP and HLA-DRA mRNA as being repeatedly associated with sepsis, and no model performed better than CRP alone (ROC-AUC 0.76 [0.68-0.84]). CONCLUSIONS: The circulating biomarkers tested were found to discriminate poorly between sepsis and non-septic SIRS, and no combination performed better than CRP alone.
    Mots-clés : Cohort, CRP, ESHR, HLA-DRA mRNA, MICROBIO, Sepsis.


  • A. Boet, G. Jourdain, S. Demontoux, S. Hascoet, P. Tissieres, C. Rucker-Martin, et D. De Luca, « Basic Hemodynamic Monitoring Using Ultrasound or Electrical Cardiometry During Transportation of Neonates and Infants », Pediatric Critical Care Medicine: A Journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies, août 2017.
    Résumé : OBJECTIVES: Electrical cardiometry and heart ultrasound might allow hemodynamic evaluation during transportation of critically ill patients. Our aims were 1) to test feasibility of stroke volume monitoring using electrical cardiometry or ultrasound during transportation and 2) to investigate if transportation impacts on electrical cardiometry and ultrasound reliability. DESIGN: Prospective, pragmatic, feasibility cohort study. SETTING: Mobile ICUs specialized for neonatal and pediatric transportation. PATIENTS: Thirty hemodynamically stable neonates and infants. INTERVENTIONS: Patients enrolled underwent paired stroke volume measurements (180 before/after and 180 during the transfer) by electrical cardiometry (SVEC) and ultrasound (SVUS). MEASUREMENTS AND MAIN RESULTS: No problems or malfunctioning occurred neither with electrical cardiometry nor with ultrasound. Ultrasound lasted on average 90 (10) seconds, while 45 (15) seconds were needed to instigate electrical cardiometry monitoring. Coefficient of variation was higher for SVUS (before/after: 0.57; during: 0.66) than for SVEC (before/after: 0.38; during: 0.36). Correlations between SVEC and SVUS before/after and during the transfer were r equal to 0.57 and r equal to 0.8, respectively (p always < 0.001). Bland-Altman analysis showed that stroke volume tends to be higher if measured by electrical cardiometry. SVEC measured before (5.5 [2.4] mL), during (5.4 [2.4] mL), and after the transfer (5.4 [2.3] mL) are similar (p = 0.955); same applies for SVUS before (2.6 [1.5] mL), during (2.4 [2] mL), and after (2.9 [2] mL) the transfer (p = 0.268). CONCLUSIONS: Basic hemodynamic monitoring is feasible during pediatric and neonatal transportation both with electrical cardiometry and ultrasound. These two techniques show comparable reliability, although stroke volume was higher if measured by electrical cardiometry. The transportation itself does not affect the reliability of stroke volume measurements.
    Mots-clés : ESHR, MICROBIO.

  • A. Breton, A. Novikov, R. Martin, P. Tissieres, et M. Caroff, « Structural and biological characteristics of different forms of V. filiformis lipid A: use of MS to highlight structural discrepancies », Journal of Lipid Research, vol. 58, nᵒ 3, p. 543-552, mars 2017.
    Résumé : Vitreoscilla filiformis is a Gram-negative bacterium isolated from spa waters and described for its beneficial effects on the skin. We characterized the detailed structure of its lipopolysaccharide (LPS) lipid A moiety, an active component of the bacterium that contributes to the observed skin activation properties. Two different batches differing in postculture cell recovery were tested. Chemical analyses and mass spectra, obtained before and after mild-alkali treatments, revealed that these lipids A share the common bisphosphorylated β-(1→6)-linked d-glucosamine disaccharide with hydroxydecanoic acid in an amide linkage. Short-chain FAs, hydroxydecanoic and dodecanoic acid, were found in a 2:1 ratio. The two lipid A structures differed by the relative amount of the hexa-acyl molecular species and phosphoethanolamine substitution of the phosphate groups. The two V. filiformis LPS batches induced variable interleukin-6 and TNF-α secretion by stimulated myelomonocytic THP-1 cells, without any difference in reactive oxygen species production or activation of caspase 3/7. Other different well-known highly purified LPS samples were characterized structurally and used as standards. The structural data obtained in this work explain the low inflammatory response observed for V. filiformis LPS and the previously demonstrated beneficial effects on the skin.
    Mots-clés : cytokines, ESHR, lipid biochemistry, lipopolysaccharide, Mass Spectrometry, MICROBIO, skin, Toll-like receptor, V. filiformis.

  • D. De Luca, A. H. van Kaam, D. G. Tingay, S. E. Courtney, O. Danhaive, V. P. Carnielli, L. J. Zimmermann, M. C. J. Kneyber, P. Tissieres, J. Brierley, G. Conti, J. J. Pillow, et P. C. Rimensberger, « The Montreux definition of neonatal ARDS: biological and clinical background behind the description of a new entity », The Lancet. Respiratory Medicine, juill. 2017.
    Résumé : Acute respiratory distress syndrome (ARDS) is undefined in neonates, despite the long-standing existing formal recognition of ARDS syndrome in later life. We describe the Neonatal ARDS Project: an international, collaborative, multicentre, and multidisciplinary project which aimed to produce an ARDS consensus definition for neonates that is applicable from the perinatal period. The definition was created through discussions between five expert members of the European Society for Paediatric and Neonatal Intensive Care; four experts of the European Society for Paediatric Research; two independent experts from the USA and two from Australia. This Position Paper provides the first consensus definition for neonatal ARDS (called the Montreux definition). We also provide expert consensus that mechanisms causing ARDS in adults and older children-namely complex surfactant dysfunction, lung tissue inflammation, loss of lung volume, increased shunt, and diffuse alveolar damage-are also present in several critical neonatal respiratory disorders.
    Mots-clés : ESHR, MICROBIO.

  • U. Lausten-Thomsen, Z. Merchaoui, C. Dubois, S. Eleni Dit Trolli, N. Le Saché, M. Mokhtari, et P. Tissières, « Ultrasound-Guided Subclavian Vein Cannulation in Low Birth Weight Neonates », Pediatric Critical Care Medicine: A Journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies, vol. 18, nᵒ 2, p. 172-175, févr. 2017.
    Résumé : OBJECTIVES: Central venous access in critically ill, small infants remains technically challenging even in experienced hands. Several vascular accesses exist, but the subclavian vein is often preferred for central venous catheter insertion in infants where abdominal malformation and/or closure of the vein preclude the use of umbilical venous catheters, as catheterization of the subclavian vein is easier in very short necks than the internal jugular vein for age-related anatomical reasons. The subclavian vein approach is yet relatively undescribed in low birth weight infants (i.e., < 2,500 g), and this study aims to explore the feasibility of this technique in very small infants. DESIGN: Retrospective data collection of prospectively registered data on central venous catheter insertion in infants. SETTING: Neonatal ICU and PICU at a university hospital. PATIENTS: One hundred and five newborn children hospitalized in at the ICU. INTERVENTIONS: An ultrasound-guided supraclavicular approach was applied on all infants who had an subclavian vein catheterization during a 30-month period from January 2013 to July 2015. MEASUREMENTS AND MAIN RESULTS: One hundred seven supraclavicular subclavian vein catheters were placed in 105 children weighing less than 5,000 g. Among those, 40 patients weighed less than 2,500 g and 10 patients weighed less than 1,500 g. Successful central venous catheter insertion, defined as the correct placement of a functional double-lumen catheter (3F or 4F), was obtained in 97.3%. All three registered failed attempts were due to hematomas from venous bleeding and occurred in infants weighing greater than 2,500 g. No case of accidental arterial puncture or pleural puncture was registered. CONCLUSIONS: This large series of subclavian vein catheterizations in small infants demonstrates the feasibility of subclavian vein catheterizations even in very small neonates weighing less than 1,500 g.
    Mots-clés : ESHR, MICROBIO.

  • U. Lausten-Thomsen et P. Tissieres, « Mothers' Milk-Can We Improve the Neonatal Immunity Response With the Oldest Recipe in the Mammal's Cookbook? », Pediatric Critical Care Medicine: A Journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies, vol. 18, nᵒ 9, p. 898-899, sept. 2017.

  • M. Levy, N. Le Sache, M. Mokhtari, G. Fagherazzi, G. Cuzon, B. Bueno, V. Fouquet, A. Benachi, S. Eleni Dit Trolli, et P. Tissieres, « Sepsis risk factors in infants with congenital diaphragmatic hernia », Annals of Intensive Care, vol. 7, nᵒ 1, 2017.

  • Z. Merchaoui, U. Lausten-Thomsen, F. Pierre, M. Ben Laiba, N. Le Saché, et P. Tissieres, « Supraclavicular Approach to Ultrasound-Guided Brachiocephalic Vein Cannulation in Children and Neonates », Frontiers in Pediatrics, vol. 5, p. 211, 2017.
    Résumé : The correct choice of intra vascular access in critically ill neonates should be individualized depending on the type and duration of therapy, gestational and chronological age, weight and/or size, diagnosis, clinical status, and venous system patency. Accordingly, there is an ongoing demand for optimization of catheterization. Recently, the use of ultrasound (US)-guided cannulation of the subclavian vein (SCV) has been described in children and neonates. This article gives an overview of the current use of US for achieving central venous catheter placement in the SCV or the brachiocephalic vein (BCV) in neonates. More than 1,250 catheters have been reported inserted in children and neonates for a cumulated success rate of 98.4% and the complication rate is reported to be low. The technical aspects of various approaches are discussed, and we offer our recommendation of an US-guided technique for SCV and BCV cannulation based on our experience in a large NICU setting. Although the cannulation the SCV or BCV does not substitute the use of peripherally inserted central catheters or umbilical venous central catheters in neonates, it is a feasible route in very small children who are in need of a large caliber central venous access.
    Mots-clés : central venous catheter, children, color, Doppler, ESHR, MICROBIO, neonatology, pediatric intensive care, ultrasonography.

  • J. Moh-Klaren, G. Bodivit, M. Jugie, P. Chadebech, L. Chevret, M. Mokhtari, X. Chamillard, P. Gallon, P. Tissières, P. Bierling, R. Djoudi, F. Pirenne, et N. Burin-des-Roziers, « Severe hemolysis after plasma transfusion in a neonate with necrotizing enterocolitis, Clostridium perfringens infection, and red blood cell T-polyagglutination », Transfusion, vol. 57, nᵒ 11, p. 2571-2577, nov. 2017.
    Résumé : BACKGROUND: Red blood cell (RBC) Thomsen-Friedenreich antigen exposure (T activation) in infants with necrotizing enterocolitis (NEC) has occasionally been associated with posttransfusional intravascular hemolysis thought to be due to anti-T antibodies in the donor plasma. STUDY DESIGN AND METHODS: We describe an infant with NEC and Clostridium perfringens infection complicated by severe hemolysis after plasma transfusion. After this case, infants with confirmed NEC were prospectively evaluated for T activation. We checked for hemolysis in patients with T activation receiving plasma-containing blood products. RESULTS: The infant had received 80 mL of fresh-frozen plasma (FFP). His RBCs displayed strong T activation, and agglutination was observed with four of six ABO-compatible FFP units. A direct antiglobulin test was negative. IgM-class anti-T antibodies were present in small amounts (titer of 8) in the transfused FFP. Anti-T antibodies from the blood donor were not hemolytic in vitro. In the prospective study, T activation was observed in three of 28 infants with NEC (11%). One infant presented moderate T activation and two infants presented very strong T activation but only moderate decreases in sialic acid expression on the RBC membrane. These three infants presented no signs of hemolysis after transfusion with unwashed blood products or FFP. CONCLUSION: Anti-T antibodies are unlikely to be the etiologic factor for the hemolytic reactions observed in infants with NEC and T activation. Massive RBC desialylation and the direct action of bacterial toxins are more probable causes. Strict avoidance of plasma-containing blood products does not seem justified in these infants.
    Mots-clés : ESHR, MICROBIO.

  • A. Novikov, A. Breton, et M. Caroff, « Micromethods for Isolation and Structural Characterization of Lipid A, and Polysaccharide Regions of Bacterial Lipopolysaccharides », Methods in Molecular Biology (Clifton, N.J.), vol. 1600, p. 167-186, 2017.
    Résumé : Lipopolysaccharides (LPS) are major components of the external membrane of most Gram-negative bacteria, providing them with an effective permeability barrier. They are essentially composed of a hydrophilic polysaccharide region (PS) linked to a hydrophobic one, termed lipid A. The LPS polysaccharide moiety is divided into the core oligosaccharide (OS) and O-chain repetitive elements. Depending on their individual variable fine structures, LPS may be potent immunomodulators. The lipid A structure is a key determinant for LPS activity. However, the presence of the core region, or at least of the highly charged 3-deoxy-d-manno-oct-2-ulosonic acid molecules, is also important for preserving the native lipid A conformation within individual LPS molecules. We describe herein four rapid and practical micromethods for LPS, lipid A, and core OS structural analyses. The first method allows the direct isolation of lipid A from whole bacteria cell mass; the second describes conditions for the sequential release of fatty acids enabling the characterization of their substitution position in the lipid A backbone, to be determined by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). The third one is a microscale procedure for the mass spectra screening of LPS, lipid A, and PS using triethylamine and citric acid. The fourth method is a chromatography procedure for Rough-type LPS on thin-layer-chromatography. These methods were developed to be coupled to mass-spectrometry (e.g., MALDI-MS) but can also be used with other analytical techniques (e.g., chromatography). Examples are given with reference to two major human pathogens: Bordetella pertussis and Pseudomonas aeruginosa; to one porcine pathogen: Actinobacillus pleuropneumoniae; and to commercial samples of Salmonella Minnesota Re595 LPS.
    Mots-clés : 3-Deoxy-d-manno-oct-2-ulosonic acid, ESHR, Gas chromatography, Lipooligosaccharide, lipopolysaccharide, Matrix-assisted laser desorption/ionization mass spectrometry, MICROBIO, Polyacrylamide gel electrophoresis, Sodium dodecyl sulfate, Thin-layer chromatography, Triethylamine.

  • M. J. Peters, A. Argent, M. Festa, S. Leteurtre, J. Piva, A. Thompson, D. Willson, P. Tissières, M. Tucci, et J. Lacroix, « The intensive care medicine clinical research agenda in paediatrics », Intensive Care Medicine, mars 2017.

  • M. Taveira, N. Yousef, J. Miatello, C. Roy, C. Claude, B. Boutillier, C. Dubois, A. - F. Pierre, P. Tissières, et P. Durand, « [Can a simple lung ultrasound score predict length of ventilation for infants with severe acute viral bronchiolitis?] », Archives De Pediatrie: Organe Officiel De La Societe Francaise De Pediatrie, déc. 2017.
    Résumé : BACKGROUND: Lung ultrasound (LU) is a bedside point-of-care technique in critical care and emergency medicine. LU is quick and non-irradiating, and provides accurate diagnostic information when compared with chest radiographs. Specific LU signs have been described for bronchiolitis. This study aimed to evaluate the correlation between severity of LU-diagnosed lung lesions, using a quantitative LU score, and the length of non-invasive ventilation (LOV) for infants diagnosed with severe viral bronchiolitis. METHODS: This was a prospective observational single-center study conducted at a level 3 pediatric intensive care unit. A LU score was calculated for 47 infants under 6 months of age with severe acute viral bronchiolitis during the 2015-2016 epidemic, and the number of intercostal spaces with consolidation or interstitial syndrome was counted for each lung. The LU score is based on the presence of A lines or B-line artifacts and consolidation (0-2 points). The modified Wood score (mWCAS) was used to define clinical severity. Other parameters such as gestational age at birth, age, supplemental oxygen (LOS), and length of stay were recorded. All LU scans were later reviewed by two trained ultrasonographers to assess the score's inter-rater reproducibility. RESULTS: The LU score on admission (3.5±2.6) did not correlate with LOV (69±68.6), mWCAS score (4±1.6), LOS (3±3.4), or length of stay (4±3.4). However, there was a significant correlation between the number of affected intercostal spaces on the right and LOS (Spearman's Rho 0.318; P=0.037). CONCLUSION: This is the first study to evaluate the use of LU in infants needing PICU admission for severe acute bronchiolitis. The LU score does not correlate with LOV, mWCAS, LOS, or length of stay, but the number of pathological intercostal spaces on the right side correlates significantly with LOS. Although LU scores have been validated for the newborn and the adult, this has been in the setting of restrictive lung diseases. Bronchiolitis is a predominantly obstructive lung disease and this may explain the lack of performance observed.
    Mots-clés : ESHR, Lung ultrasound score, MICROBIO, Non-invasive ventilation, Viral bronchiolitis.

  • D. Zhivaki, S. Lemoine, A. Lim, A. Morva, P. - O. Vidalain, L. Schandene, N. Casartelli, M. - A. Rameix-Welti, P. - L. Hervé, E. Dériaud, B. Beitz, M. Ripaux-Lefevre, J. Miatello, B. Lemercier, V. Lorin, D. Descamps, J. Fix, J. - F. Eléouët, S. Riffault, O. Schwartz, F. Porcheray, F. Mascart, H. Mouquet, X. Zhang, P. Tissières, et R. Lo-Man, « Respiratory Syncytial Virus Infects Regulatory B Cells in Human Neonates via Chemokine Receptor CX3CR1 and Promotes Lung Disease Severity », Immunity, vol. 46, nᵒ 2, p. 301-314, févr. 2017.
    Résumé : Respiratory syncytial virus (RSV) is the major cause of lower respiratory tract infections in infants and is characterized by pulmonary infiltration of B cells in fatal cases. We analyzed the B cell compartment in human newborns and identified a population of neonatal regulatory B lymphocytes (nBreg cells) that produced interleukin 10 (IL-10) in response to RSV infection. The polyreactive B cell receptor of nBreg cells interacted with RSV protein F and induced upregulation of chemokine receptor CX3CR1. CX3CR1 interacted with RSV glycoprotein G, leading to nBreg cell infection and IL-10 production that dampened T helper 1 (Th1) cytokine production. In the respiratory tract of neonates with severe RSV-induced acute bronchiolitis, RSV-infected nBreg cell frequencies correlated with increased viral load and decreased blood memory Th1 cell frequencies. Thus, the frequency of nBreg cells is predictive of the severity of acute bronchiolitis disease and nBreg cell activity may constitute an early-life host response that favors microbial pathogenesis.
    Mots-clés : Breg cell, bronchiolitis, ESHR, MICROBIO, Newborn, respiratory syncytial virus.


  • S. M. Basheer, V. Bouchez, A. Novikov, L. A. Augusto, N. Guiso, et M. Caroff, « Structure activity characterization of Bordetella petrii lipid A, from environment to human isolates », Biochimie, vol. 120, p. 87-95, janv. 2016.
    Résumé : Bordetella petrii, a facultative anaerobic species, is the only known member of the Bordetella genus with environmental origin. However it was also recently isolated from humans. The structures of the B. petrii lipid A moieties of the endotoxins were characterized here for the first time for an environmental strain and compared to that of human isolates. Characterization was achieved using chemical analyses, gas chromatography-mass spectrometry, and Matrix Assisted Laser Desorption Ionisation mass spectrometry. The analyses revealed that the different lipid A structures contain a common bisphosphorylated β-(1→6)-linked d-glucosamine disaccharide with hydroxytetradecanoic acid in amide as well at the C-3' in ester linkages. Similar to Bordetella pertussis and Bordetella bronchiseptica lipids A, the hydroxytetradecanoic acid at the C-2' position was substituted by tetradecanoic acid. Unlike B. pertussis, the hydroxytetradecanoic acid at the C-2 position was substituted with either 12:0 or 14:0 and/or their 2-OH forms. Depending on the environmental or human origin the structures differed in the length and degree of fatty acid acylation and impacted the IL-6 and TNF-α inflammatory responses tested. In one isolate we showed the presence at the C-3 position of the short-chain 10:0(3-OH), which according to our previous analyses is more characteristic of the human pathogens in the genus like B. pertussis and Bordetella parapertussis.
    Mots-clés : Bordetella, Bordetella petrii, Cell Line, Tumor, Endotoxin, ESHR, Female, Humans, Interleukin-6, Lipid A, Male, Mass Spectrometry, MICROBIO, Monocytes, Structure-Activity Relationship, Structure–activity, Tumor Necrosis Factor-alpha.

  • L. Morin, S. Ray, C. Wilson, S. Remy, M. R. Benissa, N. J. G. Jansen, E. Javouhey, M. J. Peters, M. Kneyber, D. De Luca, S. Nadel, L. J. Schlapbach, G. Maclaren, P. Tissieres, et ESPNIC Refractory Septic Shock Definition Taskforce the Infection Systemic Inflammation Sepsis section of ESPNIC, « Refractory septic shock in children: a European Society of Paediatric and Neonatal Intensive Care definition », Intensive Care Medicine, vol. 42, nᵒ 12, p. 1948-1957, déc. 2016.
    Résumé : PURPOSE: Although overall paediatric septic shock mortality is decreasing, refractory septic shock (RSS) is still associated with high mortality. A definition for RSS is urgently needed to facilitate earlier identification and treatment. We aim to establish a European society of paediatric and neonatal intensive care (ESPNIC) experts' definition of paediatric RSS. METHODS: We conducted a two-round Delphi study followed by an observational multicentre retrospective study. One hundred and fourteen paediatric intensivists answered a clinical case-based, two-round Delphi survey, identifying clinical items consistent with RSS. Multivariate analysis of these items in a development single-centre cohort (70 patients, 30 % mortality) facilitated development of RSS definitions based on either a bedside or computed severity score. Both scores were subsequently tested in a validation cohort (six centres, 424 patients, 11.6 % mortality). RESULTS: From the Delphi process, the draft definition included evidence of myocardial dysfunction and high blood lactate levels despite high vasopressor treatment. When assessed in the development population, each item was independently associated with the need for extracorporeal life support (ECLS) or death. Resultant bedside and computed septic shock scores had high discriminative power against the need for ECLS or death, with areas under the receiver operating characteristics curve of 0.920 (95 % CI 0.89-0.94), and 0.956 (95 % CI 0.93-0.97), respectively. RSS defined by a bedside score equal to or higher than 2 and a computed score equal to or higher than 3.5 was associated with a significant increase in mortality. CONCLUSIONS: This ESPNIC definition of RSS accurately identifies children with the most severe form of septic shock.
    Mots-clés : Acidosis, Cardiac, ESHR, Failure, Lactic, MICROBIO, Paediatrics, Resuscitation, Septic, Shock.

  • W. van Herk, S. el Helou, J. Janota, C. Hagmann, C. Klingenberg, E. Staub, E. Giannoni, P. Tissieres, L. J. Schlapbach, A. M. C. van Rossum, S. B. Pilgrim, et M. Stocker, « Variation in Current Management of Term and Late-preterm Neonates at Risk for Early-onset Sepsis: An International Survey and Review of Guidelines », The Pediatric Infectious Disease Journal, vol. 35, nᵒ 5, p. 494-500, mai 2016.
    Résumé : BACKGROUND: Uncertainty about the presence of infection results in unnecessary and prolonged empiric antibiotic treatment of newborns at risk for early-onset sepsis (EOS). This study evaluates the impact of this uncertainty on the diversity in management. METHODS: A web-based survey with questions addressing management of infection risk-adjusted scenarios was performed in Europe, North America, and Australia. Published national guidelines (n = 5) were reviewed and compared with the results of the survey. RESULTS: 439 Clinicians (68% were neonatologists) from 16 countries completed the survey. In the low-risk scenario, 29% would start antibiotic therapy and 26% would not, both groups without laboratory investigations; 45% would start if laboratory markers were abnormal. In the high-risk scenario, 99% would start antibiotic therapy. In the low-risk scenario, 89% would discontinue antibiotic therapy before 72 hours. In the high-risk scenario, 35% would discontinue therapy before 72 hours, 56% would continue therapy for 5-7 days, and 9% for more than 7 days. Laboratory investigations were used in 31% of scenarios for the decision to start, and in 72% for the decision to discontinue antibiotic treatment. National guidelines differ considerably regarding the decision to start in low-risk and regarding the decision to continue therapy in higher risk situations. CONCLUSIONS: There is a broad diversity of clinical practice in management of EOS and a lack of agreement between current guidelines. The results of the survey reflect the diversity of national guidelines. Prospective studies regarding management of neonates at risk of EOS with safety endpoints are needed.
    Mots-clés : Australia, Case Management, ESHR, Europe, Guideline Adherence, Guidelines as Topic, Health Policy, Humans, Infant, Newborn, MICROBIO, Neonatal Sepsis, North America, Surveys and Questionnaires.


  • S. Lemoine, B. Jaron, S. Tabka, C. Ettreiki, E. Deriaud, D. Zhivaki, C. Le Ray, O. Launay, L. Majlessi, P. Tissieres, C. Leclerc, et R. Lo-Man, « Dectin-1 activation unlocks IL12A expression and reveals the TH1 potency of neonatal dendritic cells », The Journal of Allergy and Clinical Immunology, vol. 136, nᵒ 5, p. 1355-1368.e1-15, nov. 2015.
    Résumé : BACKGROUND: Early life is characterized by a high susceptibility to infection and a TH2-biased CD4 T-cell response to vaccines. Toll-like receptor (TLR) agonists are currently being implemented as new vaccine adjuvants for TH1 activation, but their translation to the field of pediatric vaccines is facing the impairment of neonatal innate TLR responses. OBJECTIVE: We sought to analyze C-type lectin receptor pathways as an alternative or a coactivator to TLRs for neonatal dendritic cell activation for TH1 polarization. METHODS: Neonatal monocyte-derived dendritic cells (moDCs) were exposed to various combinations of TLR agonists with or without Dectin-1 agonist. IL-12 and IL-23 responses were analyzed at the transcriptional and protein levels after stimulation. The intracellular pathways triggered by combined TLR plus Dectin-1 stimulation was determined by using pharmacologic inhibitors. The capacity of neonatal moDCs to differentiate naive CD4 TH cells was evaluated in cocultures with heterologous neonatal naive T cells. Curdlan was finally tested as an adjuvant within a subunit tuberculosis vaccine in neonatal mice. RESULTS: Simultaneous coactivation through Dectin-1 and TLRs induced robust secretion of IL-12p70 by neonatal moDCs by unlocking transcriptional control on the p35 subunit of IL-12. Both the spleen tyrosine kinase and Raf-1 pathways were involved in this process, allowing differentiation of neonatal naive T cells toward IFN-γ-producing TH1 cells. In vivo a Dectin-1 agonist as adjuvant was sufficient to induce TH1 responses after vaccination of neonatal mice. CONCLUSION: Coactivation of neonatal moDCs through Dectin-1 allows TLR-mediated IL-12p70 secretion and TH1 polarization of neonatal T cells. Dectin-1 agonists represent a promising TH1 adjuvant for pediatric vaccination.
    Mots-clés : adjuvant, Adjuvants, Immunologic, Animals, Animals, Newborn, C-type lectin receptor, Cell Differentiation, Dendritic Cells, ESHR, Humans, Immunity, Innate, innate immunity, Interleukin-12, Interleukin-12 Subunit p35, Lectins, C-Type, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, MICROBIO, Monocytes, Newborn, Proto-Oncogene Proteins c-raf, T(H)1, Th1 Cells, Th2 Cells, Toll-like receptor, Vaccination.

  • F. Longhini, G. Jourdain, F. Ammar, M. Mokthari, C. Boithias, O. Romain, E. Letamendia, P. Tissieres, J. L. Chabernaud, et D. De Luca, « Outcomes of Preterm Neonates Transferred Between Tertiary Perinatal Centers », Pediatric Critical Care Medicine: A Journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies, vol. 16, nᵒ 8, p. 733-738, oct. 2015.
    Résumé : OBJECTIVE: To verify if preterm neonates transferred between tertiary referral centers have worse outcomes than matched untransferred infants. DESIGN: Cohort study with a historically matched control group. SETTING: Two tertiary-level neonatal ICUs. PATIENTS: Seventy-five neonates per group. INTERVENTIONS: Transfer between tertiary-level neonatal ICUs carried out by a fully equipped transportation team. MEASUREMENTS AND MAIN RESULTS: We measured in-hospital mortality, frequency of intraventricular hemorrhage greater than 2nd grade, periventricular leukomalacia, necrotizing enterocolitis greater than or equal to grade 2, bronchopulmonary dysplasia, composite outcomes (in-hospital mortality/bronchopulmonary dysplasia, in-hospital mortality/intraventricular hemorrhage > 2nd grade, and bronchopulmonary dysplasia/periventricular leukomalacia/intraventricular hemorrhage > 2nd grade), length of neonatal ICU stay, weight at discharge, and time spent on ventilatory support. Seventy-five similar (except for antenatal steroids administration) neonates were enrolled in each cohort. Cohorts did not differ in mortality, bronchopulmonary dysplasia, intraventricular hemorrhage greater than 2nd grade, periventricular leukomalacia, necrotizing enterocolitis greater than or equal to grade 2, any composite outcomes, neonatal ICU stay, weight at discharge, and duration of respiratory support. Results were unchanged adjusting for antenatal steroids. CONCLUSIONS: Neonatal transfer between tertiary-level centers does not impact on clinical outcomes, if performed under optimal conditions.
    Mots-clés : Apgar Score, Birth Weight, Cohort Studies, ESHR, Female, Gestational Age, Hospital Mortality, Humans, Infant, Infant Mortality, Infant, Newborn, Infant, Premature, Intensive Care Units, Neonatal, Length of Stay, Male, MICROBIO, Patient Transfer, Respiration, Artificial, Tertiary Care Centers.

  • W. Zhang-Sun, L. A. Augusto, L. Zhao, et M. Caroff, « Desulfovibrio desulfuricans isolates from the gut of a single individual: structural and biological lipid A characterization », FEBS letters, vol. 589, nᵒ 1, p. 165-171, janv. 2015.
    Résumé : The levels of sulfate-reducing bacteria (SRB), including Desulfovibrionaceae, in the gut increase following a fat-enriched diet. Endotoxins from gut microbiota contribute to the inflammation process, leading to metabolic diseases. Thus, we sought to characterize the lipid A structures of Desulfovibrionaceae lipopolysaccharides (LPS) that are associated with the microbiota inflammatory properties. LPS variants were obtained from two SRB isolates from the gut of a single individual. These LPS variants shared similar lipid A moieties with Enterobacterial LPS, but differed from one another with regard to fatty-acid numbers and endotoxic activity. This first complete structural characterization of Desulfovibrio lipid A gives new insights into previously published data on Desulfovibrio lipid A biosynthesis. LPS microdiversity within SRBs illustrates how adaptation can influence pro-inflammatory potential.
    Mots-clés : Carbohydrate Conformation, Cytokine, Desulfovibrio desulfuricans, Desulfovibrionaceae, Endotoxin, ESHR, Humans, Inflammation, Intestines, Lipid A, Mass Spectrometry, MICROBIO.
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Publications Principales avant 2015

-  Biofilms formed by gram-negative bacteria undergo increased lipid a palmitoylation, enhancing in vivo survival. Chalabaev S, Chauhan A, Novikov A, Iyer P, Szczesny M, Beloin C, Caroff M, Ghigo JM. MBio. 2014 Aug 19 ;5(4). pii : e01116-14. doi : 10.1128/mBio.01116-14.

-  Essouri S, Laurent M, Chevret L, Durand P, Ecochard E, Gajdos V, Devictor D, Tissières P. Improved clinical and economic outcomes in severe bronchiolitis with pre-emptive nCPAP ventilatory strategy. Intensive Care Med. 2014 Jan ;40(1):84-91.

-  Borckink I, Essouri S, Laurent M, Albers MJ, Burgerhof JG, Tissières P,Kneyber MC. Infants with severe respiratory syncytial virus needed less ventilator time with nasal continuous airways pressure then invasive mechanical ventilation. Acta Paediatr. 2014 Jan ;103(1):81-5.

-  Shah NR, Moksa M, Novikov A, Perry MB, Hirst M, *Caroff M*, Fernandez RC. Draft Genome Sequences of Bordetella hinzii and Bordetella trematum. Genome Announc. 2013 Oct 24 ;1(5).

-  Novikov A, Shah NR, Albitar-Nehme S, Basheer SM, Trento I, Tirsoaga A, Moksa M, Hirst M, Perry MB, Hamidi AE, Fernandez RC, *Caroff M*. Complete Bordetella avium, Bordetella hinzii and Bordetella trematum lipid A structures and genomic sequence analyses of the loci involved in their modifications. Innate Immun. 2013 Oct 14.

-  Albitar-Nehme S, Basheer SM, Njamkepo E, Brisson JR, Guiso N, Caroff M, (2013), Comparison of lipopolysaccharide structures of Bordetella pertussis clinical isolates from pre- and post-vaccine era, Carbohydr Res. 2013 Aug 30 ;378:56-62

-  Le Moigne V, Le Moigne D, *Mahana W*. Antibody response to Mycobacterium tuberculosis p27-PPE36 antigen in sera of pulmonary tuberculosis patients. Tuberculosis. 2013 Mar ;93(2):189-91.

-  Fallouh H, *Mahana W*. Antibody to heat shock protein 70 (HSP70) inhibits human T-cell lymphoptropic virus type I (HTLV-I) production by transformed rabbit T-cell lines. Toxins (Basel). 2012 Oct ;4(10):768-77.

-  Caroff M and Novikov A, (2011), Micromethods for lipid a isolation and structural characterization, Methods Mol Biol, 739:135-46

-  Chafchaouni‐Moussaoui I, Novikov A, Bhrada F, Perry MB, Filali‐Maltouf Aand Caroff M, (2011), A new rapid and micro‐scale hydrolysis, using triethylamine citrate, for lipopolysaccharide characterization by mass spectrometry, Rapid Comm. Mass Spectrom, 2011, 25:2043-48

-  Basheer SM, Guiso N, Tirsoaga A, Caroff M and Novikov A, (2011), Structural modifications occurring in lipid A of Bordetella bronchiseptica clinical isolates as demonstrated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, Rapid Commun Mass Spectrom, 25(8):1075-81

-  Marr N , Novikov A *, Hajjar AM, Caroff M, Fernandez RC, (2010), Variability in the lipid A structure and endotoxicity of Bordetella pertussis Tohama I and mouse challenge strain 18-323, J. Infect.
Dis, 202(12):1897-906

-  Vallet-Gely I, Opota O, Boniface A, Novikov A, Lemaitre B, (2010), A secondary metabolite acting as a signaling molecule controls Pseudomonas entomophila virulence, Cell Microbiol, sous presse

-  Marr N, Hajjar AM, Shah NR, Novikov A, Yam CS, Caroff M and Fernandez RC, (2010), Substitution of the Bordetella pertussis lipid A phosphate groups with glucosamine is required for robust NF-kappaB activation and release of proinflammatory cytokines in cells expressing human but not murine Toll-like receptor 4-MD-2-CD14, Infect Immun, 78(5):2060-9

-  Vallet-Gely I, Novikov A, Augusto L, Liehl P, Bolbach G, Pechy-Tarr M, Cosson P, Keel C, Caroff M and Lemaitre B, (2010), Association of hemolytic activity of Pseudomonas entomophila, a versatile soil bacterium, with cyclic lipopeptide production, Appl Environ Microbiol, 76(3):910-21

-  Ciornei CD, Novikov A, Beloin C, Fitting C, Caroff M, Ghigo JM, Cavaillon JM and Adib-Conquy M, (2010), Biofilm-forming Pseudomonas aeruginosa bacteria undergo lipopolysaccharide structural modifications and induce enhanced inflammatory cytokine response in human monocytes, Innate Immun, 16(5):288-301

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